CN1313765A - Therapeutic composition based on flavonoids for use in the treatment of tumours with cytotoxic agents - Google Patents

Abstract

The invention concerns a composition having an activity on the proliferation of clonogenic cells in tumours and comprising a therapeutically efficient amount of a flavonoid, in particular a compound selected among the compounds of formula (I) wherein: R1, R2, R3 and R4, R5 and R6 are as defined in Claim 2. Said composition is designed for use in the treatment of tumours with cytotoxic agents.

Description

Be used for therapeutic combination based on flavonoid with cytotoxic agent treatment tumor

The present invention relates in cytotoxic agent treatment tumor, use flavonoid type chemical compound.

Tumor is a kind of disease of somatic cell gene, and in pathological process, along with the continuous progress of tumor from the premalignant lesion state to the vicious transformation state, hereditary functional disorder constantly worsens, and carcinoma begins to shift and usually produce the resistance of pair cell drug toxicity.

In all developed countries, although very big effort has been done in chamber and clinical research by experiment, the mortality rate of various tumors (solid tumor and hematological system tumor) is still very high.In many countries, the mortality rate of tumor is only second to cardiovascular disease, is in second.

With regard to the tumor of making a definite diagnosis recently, the distribution proportion between solid tumor and hematology (swollen marrow, blood, the lymphsystem) tumor be in 10 tumors 9 be solid tumor.Different with the viewed result of hemooncology (hemocyte tumor treatment success rate is 40-90%), only having very, the later stage or the dissemination solid tumor of peanut respond to only several chemotherapies.Part is owing to this reason, and U.S.'s tumour patient general mortality rate during 1973 to 1992 increases.

Unfortunately, this trend might not be reversed because of the appearance of the new type antineoplastic medicine except that existing chemotherapeutic drug.Said new type antineoplastic medicine is as comprising taxanes (paclitaxel and the docetaxel) (W.P.McGuire etc. that disturb microtubule to form, Am.Intern.Med., 1989), the deutero-type inhibitor of camptothecine (topotecan and irinotecan), Hua Chun Rui Bin (by the deutero-new alkaloid of Xiao Hua spring flower), gemcitabine (new cytotoxicity antimetabolite), auspicious too West Germany's (thymidine synthetase inhibitors) or the sweet Tai Fuxin (first kind of representative drugs in the phosphocholine Arrcostab family) of replacing.These curatives are selected as first or second are selected, and are increased to that doxorubicin, cisplatin, vincristine, methotrexate, 5-fluorouracil etc. are now clear to be familiar with in the medicine of its specific activity.

At present the chemotherapeutical problem the most difficult of antitumor is because there is sizable resistance in many malignant cells colony to known cytotoxic substance performance.This situation be mostly since exist the multi-drug resistance gene or since some tumor genetic mutation constantly takes place.Therefore, oncotherapy need provide and can replenish existing means, more successfully suppress tumor diffusion and heterogeneous and suppress the new means that " many cells drug toxicity " resistance produces.

In these new means, more existing prospects are pretty good.Here it is cell death inducing, suppress tumor-blood-vessel growth and transfer process, also have gene therapy or immunization therapy certainly.

The inventor's interest is a kind of different means, and purpose is to make tumor cell colony antagonism oncotherapy responsive more, to obtain the benefit of two aspects:

1) improve cytotoxic activity and and then improve treatment and render a service,

2) frequency and seriousness that some effect of paying takes place have been reduced because of having reduced dosage (may be) owing to improved antitumor effectiveness.

This strategy is based on, and finds to have faint anti-tumor capacity or lacks some material of this ability, and the cytotoxic activity that can lure known antitumor drug into significantly improves this novel mechanism and proposes.This novel mechanism derives from these materials might stimulate the interior clone of tumor that raising of cell taken place, and makes it more responsive to the conventional therapy that uses cytotoxic agent to carry out, or suppresses to clone the propagation that cell takes place, thereby help disappearing of tumor.

Therefore a theme of the present invention is, is treating in the tumor with at least a antitumor agent that is selected from cytotoxic agent, uses the activated chemical compound of propagation to clone's generation cell that is selected from flavonoid, particularly following structural formula (I): Wherein

-R ₁, R ₂, R ₃And R ₄Be selected from H, OH, C independently of one another ₁-C ₄Alkoxyl and-OCOR ₇Group, R ₇Be C ₁-C ₄Alkyl, R ₁, R ₂, R ₃Or R ₄In at least one substituent group be not H, and R ₂And R ₃May form the (methylenedioxy) group together;

-R ₅Be selected from H, OH, C ₁-C ₄Alkoxyl and O-glycosyl;

-R ₆Be selected from cyclohexyl, phenyl and be selected from H, OH and C ₁-C ₄The group of alkoxyl replaces 1-3 time phenyl group;-and Be two keys or singly-bound.

These cytotoxic agents can use with its routine dose, and at this moment it is renderd a service and improves, thereby perhaps consider the lower dosage of raising use that its antitumor is renderd a service.

Thereby another theme of the present invention is a kind of by stimulating proliferation and raise or by suppressing the generation that propagation disturbs the clone that cell takes place the activated compositions of cell proliferation is taken place the clone, and it contains the flavonoid for the treatment of effective dose, particularly is selected from the formula I chemical compound of following formula: compound:

Wherein

-R ₁, R ₂, R ₃And R ₄Be selected from H, OH, C independently of one another ₁-C ₄Alkoxyl and-OCOR ₇Group, R ₇Be C ₁-C ₄Alkyl, R ₁, R ₂, R ₃Or R ₄In at least one substituent group be not H, and R ₂And R ₃May form the (methylenedioxy) group together;

-R ₅Be selected from H, OH, C ₁-C ₄Alkoxyl and O-glycosyl;

-R ₆Be selected from cyclohexyl, phenyl and be selected from H, OH and C ₁-C ₄The group of alkoxyl replaces 1-3 time phenyl group;-and

Be two keys or singly-bound.

Another theme of the present invention is the application in the medicine of the formula I chemical compound that particularly is defined as above of the flavonoid generation that is used in preparation disturbing (by inducing or inhibitory action) tumor clone that cell takes place during with at least a cytotoxic agent treatment.

With cytotoxic agent tumor is being carried out in the chemotherapy, can be in the chemotherapeutical incipient stage, take in single agent in mode or treatment beginning several days (for example 5 to 7 days), and according to the chemotherapy program, at the incipient stage of each treatment cycle (for example 2 to 5 days) flavonoid that comes into operation, the particularly chemical compound of structure formula I.

Preferably with 5 to 50mg/kg/ days or 200 to 2000mg/m ²The dosage in/sky is with the chemical compound of infusing method (generally in 1 to the 3 hour) formula I that comes into operation.

For the generation performance maximum effect of cell is taken place by the clone, should make the chemical compound that is come into operation obtain high as far as possible tissue concentration.

For acute stages treated, preferably use intravenous route:

-use infusion device and according to the flow velocity of recommending, with the intravenous infusion method former state instant transfusion (bag, bottle etc.) that comes into operation:

-using drug solvent well known by persons skilled in the art, the dried frozen aquatic products that suspends again is to obtain intravenous infusion liquid;

-in order to keep treatment, also can benefit oral coming into operation and adopt oral route during cytostatic agent in chemotherapy.For this purpose, can use oral freeze-dried dose (per os or tongue week absorb), directly or slow releasing tablet, oral solution, suspensoid, granule, capsule etc.

The chemical compound of formula I is the chemical compound of natural origin mostly, or the derivant of native compound.For example can mention:

1) flavonoid, for example:

-Quercetin,

-4-Sunkatol No. 1,

-6-Sunkatol No. 1,

-7-Sunkatol No. 1,

-5-methoxy flavone,

-6-methoxy flavone,

-7-methoxy flavone,

-2-cyclohexyl-5-hydroxyl chromone,

-2-cyclohexyl-6-hydroxyl chromone,

-2-cyclohexyl-7-hydroxyl chromone,

-wogonin or 5,7-dihydroxy-8-methoxy flavone,

-acacetin or 5,7-dihydroxy-4 '-methoxy flavone,

-linum element or 5,6,3 ', 4 '-tetrahydroxy-7-methoxy flavone,

-apigenin or 5,7,4 '-trihydroxyflavone,

-luteolin or 5,7,3 ', 4 '-kaempferol,

-noroxylin or 5,

-scutellarein or 5,6,7,4 '-kaempferol,

-fisetin or 7,3 ', 4 '-trihydroxyflavone alcohol,

-3,7-dihydroxy-2-(3,4,5-trihydroxy-phenyl)-chromen-4-one or 7,3 ', 4 ', 5 '-tetrahydroxyflavonol,

-kaempferol or 5,7,4 '-trihydroxyflavone alcohol,

-kaemnferide or 5,7-dihydroxy-4 '-methoxyflavonol,

-morin or 5,7,2 ', 4 '-tetrahydroxyflavonol,

-myricetin or 5,7,3 ', 4 ', 5 '-pentahydroxyflavone alcohol, 2) flavanol compound, for example:

-aromadendrin or 5,7,4 '-the trihydroxy flavonol,

-dihydrofisetin or 7,3 ', 4 '-the trihydroxy flavonol,

-hydroxyl 3,7-dihydroxy-2-(3,4,5-trihydroxy-phenyl)-chromen-4-one or 7,3 ', 4, ', 5 '-tetra-hydroxy flavanol,

-taxifolin or 5,7,3 ', 4 '-tetra-hydroxy flavanol 3) flavanone, for example:

-naringenin or 5,6,4 '-the trihydroxy flavanone,

-7,4 '-the dihydroxy flavanone,

-eriodictyol or 5,7,3 ', 4 '-the tetrahydroxy flavanone,

-hesperetin or 5,7,3 '-the trihydroxy flavanone.Preferred chemical compound is a flavone.Cytotoxic agent can be selected from: ⅰ) intercalator, particularly daunorubicin, epirubicin, idarubicin, zorubicin, aclarubicin, pirarubicin, acridine, mitoxantrone, actinomycin D, acetic acid are liked

Sprinkle for woods; ⅱ) alkylating agent is selected from platinum derivatives (cisplatin, carboplatin, oxaliplatin); ⅲ) be selected from the chemical compound that other organize alkylating agents:

-cyclophosphamide, ifosfamide, chlormethine, melphalan, chlorambucil, female

The department spit of fland,

-busulfan, ametycin,

-nitroso ureas: BCNU (carmustine), CCNU (lomustine), Fu Mosi

Spit of fland, chain are helped many stars,

-triazole or derivant: procarbazine, decarburization crust hydrazine,

-pipobroman,

-ethylidene imido amine: altretamine, triethylene thiophosphoramide ⅳ) is selected from the chemical compound that other organize antimetabolites:

Antifol: methotrexate, raltitrexed,

-antipyrimidine: 5-fluorouracil (5-FU), cytosine arabinoside (Ara-C),

-hydroxyurea,

-antipurine: purinethol, thioguanine, pentostatin, cladribine,

-cytotoxicity nucleoside synthesizes derivant: gemcitabine ⅴ) is selected from the chemical compound that tubulin is had other group medicaments of affinity:

The Changchun alkaloid of-destruction mitosis spindle: vincristine, vinblastine, length

Fields for spring sowing suffering, navelbine,

-blocking-up mitosis spindle removes polymeric medicament: paclitaxel, docetaxcl,

-pass through the destructive medicament of type inhibitory action inducing DNA: rely on pool

Glycoside, teniposide,

The type inhibitor of-induce dna fracture: topotecan, Yi Li replace

Health ⅵ) is cut into DNA segmental decomposition agent, as bleomycin, and ⅶ) one of following compounds: mithramycin, altheine enzyme, rice holder croak azoles,

Dacarbazine, ⅷ) antitumor progestogenic steroid: medroxyprogesterone, megestrol, ⅸ) antitumor estrogens sterin: diethylstilbestrol, fostestrol four sodium, ⅹ) estrogen antagonist: his English former times sweet smell, droloxifene, raloxifene, aminoglutethimide, ⅹ ⅰ) steroid antiandrogen (as cyproterone) or on-steroidal antiandrogen (fluorine

His amine, nilutamide).

Specifically, the chemical compound of formula I can be share with all treatments of using the chief cell toxic agents, be used for the polyvoltine treatment of solid tumor, these cytotoxic agents comprise:

-alkylating agent: oxynitride phosphor mix English (cyclophosphamide, ifosfamide, phenyalamine mustard,

L-PAM)

-nitroso ureas

-ametycin

-antimetabolite such as methotrexate, 5-FU, Ara-C, Capacitabine

The medicament of-interference tubulin: Changchun alkaloid (vincristine, vinblastine, ground, Changchun

Hot, navelbine), Ramulus et folium taxi cuspidatae alkaloid (paclitaxel, docetaxel), table Rhizoma Dysosmae Versipellis

Toxin (etoposide, teniposide)

-bleomycin

-type inhibitor: topotecan, irinotecan.

Equally, also the chemical compound of formula I can be share with the treatment of using the chief cell toxic agents, is used for the treatment of neoplastic hematologic disorder:

-Hokdkin disease: cyclophosphamide, chlormethine, chlorambucil, melphalan, different ring phosphorus

Amide, etoposide, doxorubicin, daunorubicin;

-acute leukemia: methotrexate, Ismipur, cytosine arabinoside, vinblastine, length

New alkali of spring, amycin, daunorubicin, altheine enzyme;

-Fei Hejiejinshi malignant lymphoma: chlormethine, chlorambucil, cyclophosphamide, American and French

Logical sequence, ifosfamide, methotrexate, cytosine arabinoside, vinblastine, vincristine,

Etoposide, amycin, daunorubicin, carmustine, lomustine, cisplatin;

-chronic lymphoid leukemia: chlormethine, chlorambucil, cyclophosphamide, L-PAM,

Ifosfamide.

Provide independent use below or unite use formula I chemical compound, prove the pharmacy test result of its character with cytotoxic agent.

The interaction (stimulating or the inhibition cell proliferation) (clone tests) that cell generates takes place in 1-and clone

Employed test is by people such as Hamburger (Science, 1977; 197,461-463) and people such as Salmon (New English J.Med., 298, he 1321-1327) describes.If cell has propagation and produces the ability of cell colony, promptly think clone's generation cell.The human tumor stem cell is the derived cell that constitutes the malignant cell of given tumor.These tumor stem cells are responsible for the recurrence process after the surgical resection primary tumo(u)r, and the formation of responsible metastatic tumor.In tumor or tumor cell line, keep the ability that it is bred under without any the solid support situation because these clones are taken place by stem cell, so be different from other tumor cells or malignant clone in the research.

In this test, with tumor cell culture on the semi-solid holder that agar constitutes.Have only its growth do not need solid support cell (be the strong tumor generation cell of person such as M.I.Dawson for " non-anchorage-dependent cell ", Cancer Res., 1995,55:4446-4451; With respect to " clonal growth ", be also referred to as the clone cell take place) can on this carrier, grow based on agar.Specifically, on such culture medium, can not survive with the normal cell (term according to M.I.Dawson is called " anchorage-dependent cell ") (for example fibroblast) of " adhesion mode " growth.In the tumor cell colony on being incubated at holder, cell (relevant with the cell division of infinite number, its colony is called " non-anchorage dependence (clone) growth " colony by Dawson) takes place and then can grow in these clones.The ratio of cell in tumor or cell line takes place these clones is 0.1% to 0.001%.Because the growth of cell (relevant with a limited number of cell division) takes place and must take place that (need have solid support (is M.I.Dawson behave said " anchorage dependence (adhesion) growth " with " adhesion mode " in non-clone, Cancer Res., 1995,55:4446-51), thus they can not grow.

Being called on the semiliquid culture medium of " soft agar ", for example cultivate breast tumor cell line MCF7 and MXT, and knot rectum cell line HT-29, to detect the influence of examination (I) chemical compound cell cluster growth.On this culture medium, having only by M.I.Dawson the clone who is called " non-anchorage dependence (clone) cell " that cell takes place can survive and grow.The tumorigenicity degree that these cells are grown and shown them in this " non-adherent adhesion " mode.Like this, suppress the growth of tumor size that the cell generation takes place wherein existing greater number clone, just become the sign that strengthens cytotoxic activity.

Otherwise this test also can disclose certain chemical compound can suppress to clone going down to posterity/breeding of generation cell, and thereby minimizing tumor cell group.

The tumor cell line of being studied is maintained 25cm ²In the falcon culture dish.Then with trypsinization and cell is fully scattered each other.The percent of living cells is detected in the blue dyeing of trypanosomicide back.Preparation concentration is 5 * 10 in 0.3% agar solution ⁴To 15 * 10 ⁴The cell suspension of cell/ml (according to the cell type of being studied).Then, with 200 μ l cell suspension inoculations in the 35mm that is added with the basal layer of forming by 0.5% agar solution (diameter) plate.200 μ l cell suspension itself are then covered by the upper strata that 1.8ml is made up of 0.3% agar solution.Then plate is placed on 5%CO ₂In 37 ℃ of couveuses of 70% humidity, pending.Handled at postvaccinal about 1 to 2 hour.With the prepared at concentrations chemical compound to be tried greater than 100 times of desired concns, and the Treatment Solution that 50 μ l are such shop spreads on the last agar layer of corresponding plate.In this research, the final concentration of the thing of test-manufacturing is 10 ^-5, 10 ^-7With 10 ^-9M.Then plate was placed 2l days at couveuse.The 21st day, inject the MTT (3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl bromination tetrazolium) of 100 μ l with RPMI 1640 preparations on the upper strata, 37 ℃ kept 3 hours.After this process, in each plate, add 2ml formalin, with the fixed cell colony.After fixing 24 hours, formalin is removed in evaporation, uses inverted microscope to detect painted colony number of cell, they by the cellularity of metabolic activity and surface area greater than 100 μ m ²

The average that cell clone takes place the clone that will count under collating condition is decided to be 100%, the percent that the average of cell clone organizes is in contrast taken place the clone who records under every kind of experiment condition being studied represent.Shown in the following tabulation 1 of the experimental result of relevant Quercetin.The table I

Cell line	Quercetin (mol.1 -1)
			????10 -5	????10 -7
	????MCF7	????67.4±3.4 ????**			????101.2±3.2 ????NS
????HT-29			????45.6±1.2 ????**	????103.4±2.2 ????NS
	????MXT	????80.8±3.6 ????**			????93.4±3.2 ????NS

The result's representative that provides in-this table is at least 6 average ± standard error (SEM)-collating condition=100%-(NS:p＞0.05 that plate is determined just; ^*: p＜0.05; ^*P＜0.01; ^{* *}: p＜0.001).

To MCF7, HT-29 and three cell lines of MXT, Quercetin can partly suppress the propagation of clone's generation cell in the tumor, promptly can induce these colony number of cell purposes significantly to reduce (reducing by 20% to 50%), and thereby can make the tumor at these cell places responsive more the conventional therapy that the use cytotoxic agent carries out with respect to collating condition.

The cytotoxic activity of cell takes place in 2-to non-clone: " MTT test "

Use the MTT colorimetric test to measure the influence that cell takes place non-clone the formula I chemical compound.

The principle of MTT test be based on the metabolic activity living cells with yellow product MTT (3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl bromination tetrazolium) mitochondrion be reduced into blue blue product first _.The first that so obtains _ amount and culture hole in the viable count that exists be directly proportional.With spectrophotography detect first _ amount.

Cell line is maintained in the plate that contains MEM 25mMHEPES minimal medium (minimum minimal medium) of with closure with 37 ℃ of monolayer culture thing forms.This culture medium is suitable for the growth of various diploids or former foster nursing breast zooblast.In this culture medium, replenish then:

-5% at 56 ℃ of FCS of 1 hour of following remove-subsidy body (hyclone)

-0.6mg/ml L-glutaminate,

-200IU/ml penicillin,

-200 μ g/ml streptomycins,

-0.1mg/ml gentamycin.

(MD USA) obtains employed 12 human tumor cell lines for ATCC, Rockville from American type culture collection.These 12 cell lines are:

-U-373MG (ATCC numbering: HTB-17) and U-87MG (ATCC numbers: HTB-

14), be two glioblastoma cell lines,

-SW1088 (the ATCC numbering: HTB-12), it is an astrocytoma cell line,

-A549 (ATCC numbering: CCL-185) and A-427 (ATCC numbers: HTB-53),

Be two non-small cell lung cancer cell systems,

-HCT-15 (ATCC numbering: CCL-225) and LoVo (ATCC numbers: CCL-

229), be two colon carcinoma cell lines,

-T-47D (ATCC numbering: HTB-133) and MCF7 (ATCC numbers: HTB-22),

Be two breast cancer cell lines,

-J82 (ATCC numbering: HTB-1) and T24 (ATCC numbers: HTB-4), be two

Individual bladder cancer cell lines,

-PC-3 (ATCC numbering: CRL-1435), be prostate cancer cell line.

At experimental session, 100 μ l are contained 20,000-50, the cell suspension inoculation of 000 cell/ml culture medium (different and different according to used cell type) are in flat 96 hole flat boards, and at 5%CO ₂With the following 37 ℃ of insulations of 70% humidity environment.Be incubated after 24 hours, changing culture medium into 100 μ l, to contain concentration range be 10 ^-5To 10 ^-10The various of M are waited to try chemical compound or are used for the culture medium that dissolving waits to test-manufacture the solvent (collating condition) of thing.After being incubated 72 hours under these conditions, change culture medium into 100 μ l are dissolved with MTT in RPMI1640 with the 1mg/ml ratio yellow solution.Flat board is incubated 3 hours once more in 37 ℃, centrifugal 10 minutes then with 400g.Remove the yellow solution of MTT, and the blue first _ crystallization that will form is dissolved among the 100 μ l DMSO on cellular level.Then with flat board vibration 10 minutes.Use Dynatech ImmunoassaySystem (immune detection system) type instrument, with 570nM and the 630nM wavelength that is equivalent to first _ maximum absorbance and background noise respectively, the cell of still surviving when detection by quantitative experiment finishes changes into yellow MTT product the intensity of the blue color of blue first _ produced.Utilize computed in software in the spectrophotometer to go out the meansigma methods of optical density and standard error of the mean (Std.Dev.) and standard error (SEM).

As an example, provide the experimental result (average optical) of flavonoid Quercetin in the following table II to 5 tumor cell line: U-373MG, T24, LoVo, MCF7 and A549.The result is to represent with respect to the result's who records under the collating condition (being equivalent to 100%) percent.The table II

Cell line	Quercetin
							10 -5*	10 -6*	10 -7	10 -8*	?10 -9*	10 -10*
	U-373MG	96.4± 3.1NS	105.2± 2.2NS	104.1± 2.9NS	98.5± 2.4NS	?101.5± ?3.2NS							97.7± 1.7NS
????T24							102.5± 0.7NS	102.4± 1.7NS	99.7± 2.0NS	107.4± 3.8NS	?105.2± ?2.0NS	110.2± 2.4**
	????LoVo	97.8± 3.1NS	94.5± 2.2NS	101.9± 4.7NS	103.1± 2.1NS	?101.6± ?3.0NS							112.0± 4.2*
????MCF7							81.5± 2.5***	84.5± 2.3***	82.1± 2.1NS	90.7± 3.8NS	?89.6± ?2.0**	103.8± 2.9NS
	????A549	86.0± 3.6*	100.3± 3.7NS	94.9± 2.3NS	98.2± 3.5NS	?97.3± ?2.2NS							97.7± 1.7NS

-concentration is with mol.1 ^-1Expression.Standard error-collating condition=100%-(NS/p＞0.05 of-xx ± yy=meansigma methods ± meansigma methods; ^*: p＜0.05; ^*: p＜0.01; P＜0.001).

These results show that Quercetin has faint anti-tumor capacity.The tight thing of this non-cell toxicity is only 10 ^-5Induce during M concentration these cell line general cell inhibition of proliferation, and this inhibitory action is no more than 20%.Under other concentration of being tested, only detect very little effect.

Determining of 3-maximum tolerated dose (MTD)

Use B6D2F1/Jico mice estimation in 4 to 6 ages in week maximum tolerated dose.Cumulative dosage with 2.5 to 160mg/kg is through the intraperitoneal approach chemical compound that comes into operation.Behind the disposable product of being studied that comes into operation, observe the survival rate of animal in 14 days, to determine MTD value (representing) with mg/kg.Also monitor the body weight of animal during this.When MTD value during, then see the MTD value as 160mg/kg greater than 160mg/kg.

The MTD value of Quercetin is considered as equaling 160mg/kg.This results highlight, this product belong to does not have direct toxic flavonoid family, can use with high tissue concentration and high dose.

Hereinafter will be given in the embodiment of formula I chemical compound using method in the list that uses cytotoxic agent or the polyvoltine therapy.A. 1 °/pulmonary carcinoma of solid tumor, 1.1 nonsmall-cell lung cancers (late period) :-recommend method (T.Le Chevalier etc., J.Clin.Oncol.1994; 12:

Increase the chemical compound of intravenous infusion formula I 360-367):

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	D 1,D 8,D 15,D 22,D 29And D 36
·navelbine	????30mg/m 2/ day	Vein	D 1,D 8,D 15,D 22,D 29And D 36
				Cisplatin	????120mg/m 2	Vein	????D 1And D 29

This treatment repeats 8 times.1.2 the CAV of small cell lung cancer (late period)-recommendation or VAC method (B.J.Roth etc., J.Clin.Oncol.1992;

Increase the flavonoid infusion 10:282-291):

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1
Cyclophosphamide	?????1000mg/m 2The injection of medicine group	Vein	????D 1
				Doxorubicin	40 to 50mg/m 2The injection of medicine group	Vein	????D 1
Vincristine	1 to 1.4mg/m 2Medicine group's injection (maximum 2mg)	Vein	????D 1

This is treated and repeated 6 times in per 21 days.Pt-E method (B.J.Roth etc., the J.Clin.Oncol.1992 of-recommendation; 10:

Increase the flavonoid infusion 282-291):

	Dosage	Approach	Natural law
				Flavonoid	?200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5
Cisplatin	????20mg/m 2/ day 20 to 60 minutes infusions	Vein	????D 1-D 5
				Etoposide	????80mg/m 2/ day 60 minutes infusions	Vein	????D 1-D 5

Repeated one-period in per 21 days, treatment comprises 6 cycles.

1.3 the non-small cell bronchogenic carcinoma of local late period or transfer:

Single chemotherapy

	Dosage	Approach	Natural law
				Flavonoid	????200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	??D 1,D 8,D 15Then 1 the week/rest
Gemcitabine	???????1000mg/m 2/ day 0.5 hour infusion	Vein	??D 1,D 8,D 15Then 1 the week/rest

Treatment can comprise and repeats this 4 cycle.

Gemcitabine/cisplatin share:

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	D 1-D 5,D 8-D 15
Gemcitabine	???1000mg/m 2/ day 0.5 hour infusion	Vein	??D 1,D 8,D 15
				Cisplatin	?????20mg/m 2/ day 20-60 minute infusion	Vein	??????D 1

Treatment comprises this 21 day cycle of repetition.2 °/breast carcinoma-CMF method is as auxiliary treatment (G.Bonnadonna etc., the N.Engl.J.Med. of the breast carcinoma of can performing the operation; 1976; 294:405-410):

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1To D 14
Cyclophosphamide	???100mg/m 2/ day	Oral	????D 1To D 14
				Methotrexate	????40mg/m 2The injection of medicine group	Vein	????D 1And D 8
·5-FU	????600mg/m 2	Vein	????D 1And D 8

Repeated one-period in per 28 days, treatment comprises 6 cycles.-AC method (B.Fisher etc., J.Clin.Oncol.; 1990; 8:1483-1496)

As auxiliary treatment:

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ horizon or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1
Doxorubicin	????60mg/m 2The injection of medicine group	Vein	????D 1
				Cyclophosphamide	????600mg/m 2The injection of medicine group	Vein	????D 1

Repeated one-period in per 21 days, treatment comprises 4 cycles.-breast carcinoma of transfer arranged :-the FAC method (A.V.Buzdar etc., Cancer 1981; 47:2537-2542)

In its various update routines, add the flavonoid infusion by following step (nonrestrictive):

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	D 1-D 5And D 8-D 12Or D 1-D 5
·5-FU	???500mg/m 2/ day medicine group	Vein	?D 1And D 8Or D 1-D 2
				Doxorubicin	????50mg/m 2Medicine group	Vein	?????D 1Or D 1And D 2
Cyclophosphamide	????500mg/m 2	Oral or vein medicine group injects	??????D 1??????D 1

Per 3 weeks repeat one-period, up to the diagnosis state of an illness new progress are arranged.

-the CAF method (G.Falkson etc., Cancer 1985; 56:219-224):

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 14
Cyclophosphamide	???100mg/m 2/ day	Oral	????D 1-D 14
				Doxorubicin	????30mg/m 2The injection of medicine group	Vein	????D 1And D 8
·5-FU	????500mg/m 2The injection of medicine group	Vein	????D 1And D 8

Per 28 days repeat one-period, up to the new development that diagnosed the illness.-in the CMF method:

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	D 1-D 5And D 8-D 12
Cyclophosphamide	???600mg/m 2/ day medicine group	Vein	????D 1And D 8
				Methotrexate	???40mg/m 2/ day medicine group	Vein	????D 1And D 8
·5-FU	???600mg/m 2/ day medicine group	Vein	????D 1And D 8

Per 3 to 5 weeks repeat this cycle, and treatment comprises 6 cycles.-in the CMF-VP method:

	Dosage	Approach	Natural law
				Flavonoid	???200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5????D 8-D 12????D 15-D 19????D 22-D 26
Cyclophosphamide	2 to 2.5mg/kg/ days	Oral	Every day
				Methotrexate	25 to 50mg/m 2/ day	Vein	D 1,D 8,D 15,D 22
·5-FU	300 to 500 mg/m 2/ day	Vein	D 1,D 8,D 15,D 22
				Vincristine	0.6 to 1.2mg/m 2/ day	Vein	D 1,D 8,D 15,D 22
Prednisone	????30mg/m 2/ day	Oral	From D 1To D 10

This is treated and repeats once in per 4 weeks.

-in the FEC method:

	Dosage	Approach	Natural law
				Flavonoid	????200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	D 1-D 5And D 8-D 12
·5-FU	???????600mg/m 2/ day	Vein	????D 1And D 8
				Epirubicin	????????50mg/m 2	Vein	????D 1
Cyclophosphamide	???????600mg/m 2	Vein	????D 1

This is treated and repeats once in per 3 weeks.-the MMC-VBC method (C.Rrambilla etc., Tumori, 1989,75:141-144) in:

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/kg/ days or 5-50mg/kg/ days 1 hour infusion	Vein	D 1-D 5And D 15-D 19
Ametycin	????10mg/m 2Medicine group	Vein	??????D 1
				Vinblastine	????50mg/m 2/ day medicine group	Vein	????D 1And D 15

This is treated and repeated once in per 28 days, up to the new progress that diagnosed the illness.-at NFL (S.E.Jones etc., J.Clin.Oncol.1991; 9:1736-1739):

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5
Mitoxantrone	????10mg/m 2Medicine group	Vein	????D 1
				·5-FU	????1000mg/m 224 hours infusions	Vein	????D 1-D 3
Folinic acid	????100mg/m 2Medicine group	Vein	????D 1

This treatment comprises 2 cycles, 21 days at interval, and needs assessment curative effect then.

Also can in having the breast carcinoma of transfer, treatment share the flavonoid infusion with the taxanes medicine, for example-and in may having the metastatic tumor of resistance to anthracycline antibiotics, treatment uses paclitaxel (F.A.

Holmes etc., J.Natl.Cancer Inst.1991; 83:1797-1805):

	Dosage	Approach	Natural law
				Flavonoid	?200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5
Paclitaxel	????175mg/m 2Infusion in 3 to 24 hours	Vein	????D 1

Per 21 days repeat one-period, up to diagnosing out disease that new progress is arranged.-cytotoxic agent chemotherapy (having used the anthracene nucleus Drug therapy) back produces resistance or recurrence,

Or late period of recurring during the auxiliary treatment or metastatic breast cancer, treat with docetaxel

(C.A.Hudis etc., J.Clin.Oncol.1996; 14:58-65):

	Dosage	Approach	Natural law
				Flavonoid	????200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5
·docetaxel	?100mg/m 2Or 60-100mg/m 21 hour (or 24 hours) infusion	Vein	????D 1

Per 21 days repeat this cycle, treat 2 cycles, or progress occurs up to disease.-in dosage reinforcement scheme, as the means of consolidating of the first selection treatment, in conjunction with transplanting together

Body medullary cell and peripheral hematopoietic stem cells, for example :-CPB method (W.P.Peters etc., J.Clin.Oncol.1993; 11:132-

1143), wherein the-1,0 and 1 day venoclysis stem cell:

	Dosage	Approach	Natural law
				Flavonoid	?200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D -6To D -1
Cyclophosphamide	????1875mg/m 2Infusion in 1 hour	Vein	????D -6To D -4
				Cisplatin	????55mg/m 2/ days 24 hours in continuous infusion	Vein	????D -6To D -4
Carmustine (BCNU)	????600mg/m 2/ days 2 hours in infusion	Vein	????D -3

-CTCb method (K.Autman etc., J.Clin.Oncol.1992; 10:102-

110), wherein the 0th day intravenous infusion stem cell:

	Dosage	Approach	Natural law
				Flavonoid	?200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D -7To D -1
Cyclophosphamide	????1500mg/m 2Continuous infusion in 24 hours (4 doses)	Vein	????D -7To D -3
				Plug is for group	????125mg/m 2Continuous infusion in 24 hours (4 doses)	Vein	????D -7To D -3
Carboplatin	????200mg/m 2Continuous infusion in 24 hours (4 doses)	Vein	????D -7To D -3

-CTM method (L.E.Damon etc., J.Clin.Oncol.1989; 7:560-

571 and I.C.Henderson etc., J.Cellular Biochem, 1994 (Suppl.

18B): 95), the 0th day venoclysis raw blood stem cell wherein:

	Dosage	Approach	Natural law
				Flavonoid	?200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D -6To D -1
Cyclophosphamide	????1500mg/m 2/ day 1 hour in infusion	Vein	????D -6To D -3
				Plug is for group	????150mg/m 2/ days 2 hours in infusion	Vein	????D -6To D -3
Mitoxantrone	????10-15mg/m 2Infusion in 1 hour	Vein	????D -6To D -3

3 °/gynecological tumor

3.1 ovarian cancer

-treat ovarian cancer, the ovarian cancer of transfer is particularly arranged:

ⅰ) PAC method (G.A.Omura etc., J.Clin.Oncol.1989; 7:457-

465), carry out the flavonoid infusion by following program:

	Dosage	Approach	Natural law
				Flavonoid	???200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5
Cisplatin	50mg/m 2(or 40-90mg/m 2) infusion in 1 to 2 hour	Vein	????D 1
				Doxorubicin	????50mg/m 2(or 30 to 50mg/m in medicine group 2)	Vein	????D 1
Cyclophosphamide	????1000mg/m 2(or 200 to 600mg/m for infusion in 1 to 2 hour 2)	Vein	????D 1

Repeated a treatment cycle in per 21 to 28 days, treatment comprises 8 cycles.ⅱ) substitute method, according to the described (Gynecol.Oncol. of people such as A.Marietta

1990；36-96)：

	Dosage	Approach	Natural law
				Flavonoid	?200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5????D 8-D 12
Altretamine	???200mg/m 2/ sky is divided into four doses	Oral	????D 1-D 15

Treatment comprises 2 cycles, 28 days at interval.ⅲ) paclitaxel method: can be at people (Ann.Intern.Med. such as W.P.McGuire

1989; 111:273-279) add flavonoid in the described paclitaxel method:

	Dosage	Approach	Natural law
				Flavonoid	??200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 3
Paclitaxel	????135mg/m 23 hours or 24 hours infusions	Vein	????D 1

Treatment comprises 2 cycles, 28 days at interval (carrying out the curative effect assessment during end).-in second system of selection, add flavonoid based on topotecan, shift with treatment and

Drug-fast ovarian cancer is arranged:

	Dosage	Approach	Natural law
				Flavonoid	?200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5
Topotecan	????1.5mg/m 2/ day 0.5 hour infusion	Vein	????D 1-D 5

Treatment comprises 2 cycles, and 21 days (the assessing during end) in interval is referring to the described (J.Clin.Oncol.1996 of people such as A.P.Kudelka; 14:1552-1557).

3.2 trophoblastic tumor:

-for low danger patient, can be at people (Semin.Surg.Oncol. such as H.Takamizaua

1987; 36-44) add in the described therapy and use flavonoid:

	Dosage	Approach	Natural law
				Flavonoid	????200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5
Methotrexate (MTX)	20mg/ days	Intramuscular	????D 1-D 5
				Actinomycin D (DACT)	0.5mg/ my god, the injection of medicine group	Vein	????D 1-D 5

(MTX-DATC method) 3.3 uterus carcinoma :-also can flavonoid and CAV (or VAC) method be share by following program:

	Dosage	Approach	Natural law
				Flavonoid	????200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5
Cyclophosphamide	????750-1200mg/m 2Infusion	Vein	????D 1
				Doxorubicin	?????45-50mg/m 2Infusion	Vein	????D 1
Vincristine	??????1.4mg/m 2	Vein	????D 1

Treatment comprises per 21 days and repeats this cycle.-in the FAP method:

	Dosage	Approach	Natural law
				Flavonoid	????200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5
Fluorouracil (5-FU)	???????600mg/m 2/ day	Vein	????D 1,D 8
				Doxorubicin	?????????30mg/m 2	Vein	????D 1
Cisplatin	?????????75mg/m 2	Vein	????D 1

Treatment comprises per 21 or 28 days and repeats this cycle.

4 °/testis and carcinoma of prostate

Also can share flavonoid in the treatment of-tumor of testis:

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5
Rich plain mycin	????30mg/m 2Infusion	Vein	????D 1
				Etoposide	???100mg/m 2/ day infusion	Vein	????D 1-D 5
Cisplatin	????20mg/m 2/ day	Vein	????D 1-D 5

Treatment comprises 3 cycles, every 2l days one-period.

5 °/bladder cancer

Can share flavonoid in-CISCA2 (the being also referred to as PAC) method:

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5
Cisplatin	????50mg/m 2	Vein	????D 1
				Cyclophosphamide	????600mg/m 2Infusion	Vein	????D 1
Doxorubicin	????75mg/m 2Infusion	Vein	????D 1

Per 3 weeks repeat one-period.

-at MVAC method (CN Sternberg etc., J.Urol.1988; 139:461-469):

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 3????D 15-D 18????D 22-D 25
Methotrexate	30mg/m 2The injection of medicine group	Vein	D 1,D 15,D 22
				Vinblastine	????3mg/m 2	Vein	D 2Or D 2,D 15,D 22
Doxorubicin	??30mg/m 2The injection of medicine group	Vein	?????????D 2
				Cisplatin	????70-100mg/m 2Carried in 1 hour	Vein	???????D 1Or D 2

Per 4 to 5 weeks in this cycle repeat once, minimum 2 cycles.6 °/nasopharyngeal carcinoma/the incidence cancer-flavonoid and polyvoltine therapy can be share, treat these tumors: 6.1 nasopharyngeal carcinoma :-ABVD method:

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	???D 1-D 3???D 8-D 10Or D 15-D 17
Doxorubicin	????30mg/m 2/ day	Vein	D 1And D 8Or D 15
				Bleomycin	????10mg/m 2/ day	Vein	D 1And D 8Or D 15
Vinblastine	????6mg/m 2/ day	Vein	D 1And D 8Or D 15
				Dacarbazine	???200mg/m 2/ day	Vein	D 1And D 8Or D 15

Per 4 weeks are one-period, and treatment repeats 1-6 cycle.6.2 the incidence cancer of transfer is arranged :-at DVAL research group (New Engl.J.M.1991; 324:1685-1690) in the described Pt-Fu method (as being used for the treatment of pharyngeal cancer):

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5
Cisplatin	????100mg/m 21 hour infusion	Vein	????D 1
				Fluorouracil	??1000mg/m 2/ day continuous infusion	Vein	????D 1-D 5

Treatment comprises 2 cycles, and per 3 weeks are one-period.7 °/soft tissue sarcoma-for example flavonoid can be introduced in the CYVADIC therapy :-(Cancer 1984 referring to people such as H.M.Pinedo; 53:1825):

	Dosage	Approach	Natural law
				Flavonoid	??200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5????D 8-D 10????D 15-D 17
Cyclophosphamide (Cy)	????500mg/m 2Medicine group	Vein	????D 2
				Vincristine (V)	???1.5mg/m 2/ day medicine group	Vein	????D 1,D 8,D 15
Doxorubicin (A)	????50mg/m 2Medicine group	Vein	????D 2
				Dacarbazine (DIC)	????250mg/m 2/ day 15 minutes infusions	Vein	????D 1-D 5

Treatment comprises that per 4 weeks repeat this cycle, at least 2 cycles.8/ has the hormone resistance carcinoma of prostate of transfer :-at people such as G.R.Hudis (J.Clin.Oncol.1992; 10:1754-1761)

In the described VBL-estramustine therapy:

	Dosage	Approach	Natural law
				Flavonoid	??200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	D 1-D 3,D 8-D 10D 15-D 17.D 22-D 24D 29-D 31,D 36-D 38
Vinblastine	????4mg/m 2/ day medicine group	Vein	D 1,D 8,D 15,D 22,D 29, ????D 36
				Estramustine	??200mg/m 2Every day 3 (600mg/m 2/ day)	Oral	Every day, totally 6 weeks

Treatment cycle continued for 6 weeks, was the rest period in 2 weeks then.9 °/germinocarcinoma

ⅰ) for prognosis tumor preferably :-according to people such as G.J.Bosl (J.Clin.Oncol.1988; 6:1231-1238)

Described Pt-E therapy:

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5
Cisplatin	???20mg/m 2/ day 20 to 60 minutes infusions	Vein	????D 1-D 5
				Etoposide (E)	???100mg/m 2/ day 1 hour infusion	Vein	????D 1-D 5

Treatment comprises 4 cycles, phase 21 or 28 days weekly.

ⅱ) tumor to shifting :-according to people such as S.D.Williams (N.Eng.J.Med.1987; 316:1435-

1440) described PEB therapy:

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5????D 9-D 11????D 16-D 18
Cisplatin (P)	??20mg/m 2/ day 20 to 60 minutes infusions	Vein	????D 1-D 5
				Etoposide (E)	??100mg/m 2/ day 1 hour infusion	Vein	????D 1,D 5,D 16
Bleomycin (B)	30U (or mg)/sky medicine group	Vein	????D 1-J 5

Treatment comprises 4 cycles, per 21 days one-periods.The renal carcinoma of 10 °/renal carcinoma-transfer: flavonoid can be introduced people (Cancer such as M.J.Wilkinson

1993; 71:3601-3604) in the described therapy:

	Dosage	Approach	Natural law
				Flavonoid	????200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5????D 8-D 15
Floxuridine	????0.075mg/m 2/ day continuous infusion	Vein	????D 1-D 14

Treatment comprises 2 cycles, 28 days at interval.-nephroblastoma: can in the DAVE therapy, introduce flavonoid:

	Dosage	Approach	Natural law
				Flavonoid	????200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 3????D 8-D 10
Radiating streptozotocin D	??????0.6mg/m 2/ day	Vein	????D 1,D 8
				Doxorubicin	??????30mg/m 2/ day	Vein	????D 1,D 8
Cyclophosphamide	????200mg/m 2/ day 1 hour infusion	Vein	????D 1,D 8

Per 3 to 4 cycle Monday.11 °/digestive tract tumor, 11.1 esophageal carcinoma :-in following FAP therapy, introduce flavonoid:

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 3????D 8-D 10
5-fluorouracil (5-FU)	????600mg/m 2	Vein	????D 1,D 8
				Doxorubicin	????30mg/m 2	Vein	????D 1
Cisplatin	????75mg/m 2	Vein	????D 1

Every 3-4 week repeats this cycle once.11.2 gastric cancer-treatment late period and/or the gastric cancer of transfer is arranged:

-EAP therapy is (referring to P.Preusser etc., J.Clin.Oncol.1989; 7:

1310)：

	Dosage	Approach	Natural law
				Flavonoid	?200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5,D 8-D 10
Etoposide	????120mg/m 2/ day 1 hour infusion	Vein	????D 3,D 4,D 5, or D 4-D 6
				Doxorubicin	????20mg/m 2/ day medicine group	Vein	????D 1,D 7
Cisplatin	?????40mg/m 2/ day 1 hour infusion	Vein	????D 2,D 8

28 days one-periods.-FAMtx therapy: referring to people such as J.A.Wils (J.Clin.Oncol.1991; 89:

827)：

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 3
Fluorouracil (5-FU) (F)	?1500mg/m 2Behind medicine group's methotrexate 1 hour	Vein	????D 1
				Doxorubicin (A)	??30mg/m 2Medicine group	Vein	????D 15
Methotrexate (Mtx)	??1500mg/m 2, 30 minutes infusions	Vein	????D 1

Treatment comprises 2 cycles at least, 28 days at interval.-for some case, can use this method or its amending method (epirubicin by following program

Replace doxorubicin):

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 3
Fluorouracil (5-FU)	????1500mg/m 2	Vein	????D 1
				Doxorubicin (A) or epirubicin (A)	???30mg/m 2The 60mg/m of medicine group 2Medicine group	Cava vein	????J 1=FAMTx ????J 1=FEMTx
Methotrexate (infusion before 5-FU)	????1500mg/m 2	Vein	????D 1
				Folinic acid	????15mg/m 2/ day	Oral	????D 2-D 4

12 °/colorectal cancer-flavonoid can be introduced the FU-levamisole auxiliary treating method of colorectal cancer (referring to C.

G.Moertel etc., N.Eng.J.Med.1990; 322:352):

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	?????D 1-D 5???D 29-D 31
5-fluorouracil	450mg/m 2/ day medicine group	Vein	?????D 1-D 5
				5-fluorouracil	??450mg/m 2Medicine group	Vein	???????D 29
Levamisole	50mg three times on the one	Oral	1 week in 3 days/all 2 weeks

Repeat the treatment of 5-FU medicine group behind the 1-5 days induction periods weekly, totally 52 weeks; Repeated to treat with the same rhythm and pace of moving things on the same day of the 5-FU medicine group of coming into operation and subsequently 2 days with flavonoid.-treatment has the colorectal cancer of drug-fast transfer to 5-FU :-according to people such as M.L.Rothenberg (J.Clin.Oncol.1996; 14:1128-

1135) described method:

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	D 1-D 3,D 9-D 10,D 15- ??D 17,D 22-D 24
Irinotecan	??125mg/m 2/ day	Vein	????D 1,D 8,D 15,D 22

Treated for 2 cycles, 42 days at interval.13 °/Kaposi sarcoma-flavonoid and following two kinds of methods are share, these methods have been used with the liposome form and have been joined

The anthracycline antibiotics of system:

ⅰ) people (J.Clin.Oncol.1995 such as P.S.Gill; 13:996-1003) and people such as C.A.Presant (Lancet 1993; 341:1242-1243) described method:

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	D 1-D 3And D 15-D 17
The liposome daunorubicin	????20mg/m 2/ day 1 hour infusion	Vein	????D 1,D 15

Treatment comprises 2 cycles of 28 days of recurrence interval, estimates curative effect then.

ⅱ) people (J.Clin.Oncol.1995 such as M.Harrison; 13:914-920) described method:

	Dosage	Approach	Natural law
				Flavonoid	????200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	??D 1-D 3
The plasmalogen doxorubicin	???????20mg/m 230 minutes infusions	Vein	????D 1

Treatment comprises 2 cycles of 28 days at interval, estimates curative effect then.14 °/metastasis melanin tumor :-also flavonoid can be incorporated in the method for the treatment of the malignant melanoma that shifts: people such as-G.Cocconi (N.Eng.J.Med.1992; 327:516) described DTIC/TAM method, treatment comprises that be one-period by following program with 21 days, repeats 4 cycles:

	Dosage	Approach	Natural law
				Flavonoid	????200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5
Dacarbazine (DTIC)	??????250mg/m 2/ day infusion [as must 15 to 30 minutes] or [as with 250ml periphery infusion, must 30 minutes] through centre pipe	Vein	????D 1-D 5
				Tamoxifen (TAM)	????20mg/m 2/ day	Oral	????D 1-D 5

Treatment comprises 4 cycles, 21 days phases weekly.15 °/neuroendocrine tumor-flavonoid can (Cancer 1991 with people such as C.G.Moertel; 68:227) described

Method is share :-Pt-E method:

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 3
Etoposide	???130mg/m 2/ day 1 hour infusion	Vein	????D 1-D 3
				Cisplatin	????45mg/m 2/ day 1 hour infusion	Vein	????D 2,D 3

Treatment comprises per 28 days 2 repetition periods.16 °/cancer of pancreas-late period pancreas adenocarcinoma: flavonoid can with people (Proc.Am.Soc.Clin. such as M.Moore

Oncol.1995; 14:473) described gemcitabine Therapeutic Method share:

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 14 o'clock infusions	Vein	D 1-D 3,D 8-D 10,D 15, D 22,D 29,D 36,D 43, D 57
Gemcitabine	????1000mg/m 20.5 hour infusion	Vein	D 1,D 8,D 15,D 22,D 29,D 36,D 43D then 57Weekly 1 time then, totally 3 weeks, 1 week and estimate curative effect of having a rest afterwards

B. 1 ° of hemooncology/adult's acute leukemia 1.1 acute lymphoblast leukemia: 1.1.1 Linker method by following program flavonoid is added in the Linker method-induce chemotherapy and consolidate chemotherapy that (referring to C.A.Linker etc., Blood 1987; 69:1242-1248 and C.A.Linker etc., Blood 1991; 78:2814-2822):

ⅰ) induce chemotherapy:

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	D 1-D 5,D 8-D 12,D 15-D 19
Daunorubicin	50mg/m 2Medicine group, (patient more than 50 years old was 30mg/m in per 24 hours 2)	Vein	????D 1,D 2,D 3
				Vincristine	2mg medicine group	Vein	???D 1,D 8,D 15,D 22
Prednisone	???60mg/m 2/ day	Oral	????D 1-D 28
				The altheine enzyme	????6000U/m 2	Intramuscular	????D 17-D 28

ⅱ) consolidate chemotherapy (option A):

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5,D 8-D 12
Daunorubicin	50mg/m 2Per 24 hours, the injection of medicine group	Vein	????D 1,D 2
				Vincristine	2mg medicine group	Vein	????D 1,D 8
Prednisone	????60mg/m 2/ natural gift 3 times	Oral	????D 1-D 14
				The altheine enzyme	????12000U/m 2	Intramuscular	D 2,D 4,D 7,D 9And D 14

Consolidate chemotherapy A and comprise 4 aforesaid consecutive periods=cycles 1,3,5 and 7.

ⅲ) consolidate chemotherapy (option b and C):

Following treatment is equivalent to described cycle 2,4,6 and 8 (option bs) and 9 (the scheme C) of consolidating as people such as C.A.Linker:

Option b:	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 14 o'clock infusions	Vein	????D 1-D 5,D 8-D 12
·Ara-C	????300mg/m 22 hours infusions	Vein	????D 1,D 4,D 8,D 11
				Teniposide	????165mg/m 22 hours infusions (4 cycles)	Vein	????D 1,D 4,D 8,D 11

Scheme C:	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5
Methotrexate	????690mg/m 242 hours continuous infusions	Vein	????D 1-D 2
				Folinic acid	????15mg/m 2Per 6 hours once	Oral	????D 2-D 5

1.1.2 Hoelzer method

Can according to following program this polyvoltine therapy (D.Hoelzer etc., Blood 1984;

64:38-47, D.Hoelzer etc., Blood 1988; 71:123-131)

Add flavonoid in the cytotoxic agent:

ⅰ) induce chemotherapy/1 phase

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5,D 8-D 12, ????D 15-D 19
Daunorubicin	????25mg/m 2	Vein	????D 1,D 8,D 15,D 22
				Vincristine	????1.5mg/m 2(maximum 2mg)	Vein	????D 1,D 8,D 15,D 22
Prednisone	?????60mg/m 2	Oral	????D 1-D 28
				The altheine enzyme	????5000U/m 2(maximum 2mg)	Intramuscular	????D 1-D 14

ⅱ) induce chemotherapy/2 phases

Finish inductive the 2nd phase by follow procedure:

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	D 29-D 33,D 36-D 40, ?D 43-D 47
Cyclophosphamide	????650mg/m 2(maximum 15mg)	Vein	????D 29,D 43,D 57,
				Cytosine arabinoside	????75mg/m 2/ day 1 hour infusion	Vein	????D 31-D 34,D 38-D 41????D 45-D 48,D 52-D 55
Purinethol	?????60mg/m 2	Oral	????D 29-D 57
				Methotrexate	????10mg/m 2/ day (maximum 15mg)	Vein	????D 31,D 38,D 45,D 52

ⅲ) induce again chemotherapy/1 phase

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5,D 8-D 12, ????D 15-D 19,D 22-D 26
Doxorubicin	????25mg/m 2/ day	Vein	????D 1,D 8,D 15,D 22
				Dexamethasone	????10mg/m 2/ day	Oral	????D 1-D 28
Vincristine	????1.5mg/m 2/ day (maximum 2mg)	Oral	????D 1,D 8,D 15And D 22

ⅳ) induce again chemotherapy/2 phases

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 31-D 35,D 38-D 42
Cyclophosphamide	????650mg/m 2(maximum: 1000mg)	Vein	????D 29
				Cytosine arabinoside	????75mg/m 2	Vein	????D 31-D 34,D 38-D 41
Thioguanine	????60mg/m 2	Oral	????D 29-D 42

1.2 acute myeloid leukemia:

1.2.1 treat the adult at any age

Can be by following program, (Leukemia 1990 for people such as former Z.A.Arlin; 4:(177-183) and people such as P.H.Wiernik (Blood 1992; 79:313-319) add flavonoid in the described treatment of mixing the standard dose cytosine arabinoside:

	Dosage	Approach	Natural law
				Flavonoid	????200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	???D 1-D 12
Cytosine arabinoside	????100-200mg/m 2/ day continuous infusion	Vein	????D 1-D 7
				Doxorubicin or mitoxantrone or idarubicin	45mg/m 2The injection of/day medicine group (as year neighbour 〉=60 years old, then is 30mg/m 2/ day) 12mg/m 2Every day, 13mg/m injected in medicine group 2Medicine group injection every day	The cava vein vein	D 1-D 3, or D 8-D 10????D 1-D 3????D 1-D 3

1.2.2 less than adult treatment in 60 years old

ⅰ) induce chemotherapy:

In the treatment of high dose cytosine arabinoside, mix this induction duration according to follow procedure:

	Dosage	Approach	Natural law
				Flavonoid	????200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 10
Cytosine arabinoside	????2000mg/m 2/ day 2 hours infusions, per 12 hours once	Vein	????D 1-D 6
				Doxorubicin or cytosine arabinoside	????60mg/m 2/ day 24 hours continuous infusion 3000mg/m 2/ day 1 hour infusion, per 12 hours once	Cava vein	????D 4-D 6????D 1-D 6
Daunorubicin	45mg/m 2The injection of per 24 hours medicine groups	Vein	????D 7-D 9

(in order to reduce the toxic danger of center of origin nervous system in the renal failure process, with the clearance rate level of cytosine arabinoside dose titration) to kreatinin,

(Leukemia 1994 referring to people such as L.E.Damon; 8:535-541); (Blood 1991 for people such as G.L.Phillips; 77:1429-1435) and people (J.Clin.Oncol.1997 such as G.Smith; 15:833-839).

ⅱ) consolidate chemotherapy:

Hereinafter described cycle repeats 8 times, per 4 to 6 weeks be one-period (referring to R.J.Mayer etc., N.Engl.J.Med.1994; 331:896-903):

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5
Cytosine arabinoside is cytosine arabinoside then	????3000mg/m 23 hours infusions, 12 hours (4 cycles) 10mg/m once 2/ days per 12 hours once	Vein is subcutaneous	????D 1,D 3,D 5????D 1-D 5
				Doxorubicin	????45mg/m 2Medicine group's (4 cycles)	Vein	????D 1

ⅲ) consolidate chemotherapy (using the high dose cytosine arabinoside)

The following cycle must repeat twice and (Blood 1991 according to people such as G.L.Phillips; 77:1429-1435), people (J.Clin.Oncol.1989 such as S.N.Wolff; 7:1260-1267), people (N.Engl.J.Med.1994 such as R.J.Mayer; 331; 896-903) described method is carried out:

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 10
Cytosine arabinoside	????3000mg/m 2Infusion was 1 hour in per 12 hours	Vein	????D 1-D 6
				Doxorubicin	??30-45mg/m 2/ day medicine group, once a day	Vein	????D 7-D 9

1.2.3 adult treatment more than 60 years old

Can add flavonoid in the chemotherapy program following the consolidation:

ⅰ) (Blood 1991 with reference to people such as R.O.Dilman; 78:2520-2526),

(Leukemia 1990 for people such as Z.A.Arlin; 4:177-183), P.H

(Blood 1992 for people such as Wiernik; 79:313-319) described method:

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 6
Cytosine arabinoside	??100-200mg/m 224 hours continuous infusions	Vein	????D 1-D 5
				Doxorubicin or mitoxantrone or idarubicin	30-45mg/m 2/ day, the 12mg/m of medicine group 2/ day, the 13mg/m of medicine group 2/ day, medicine group	The cava vein vein	????D 1,D 2????D 1,D 2????D 1,D 2

ⅱ) people (N.Engl.J.Med.194 such as R.L.Mayer; 331:896-903)

Described method:

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 6
Cytosine arabinoside is cytosine arabinoside then	????100mg/m 224 hours continuous infusion (4 cycles) 100mg/m 2Per 12 hours once	Vein is subcutaneous	????D 1-D 5????D 1,D 5
				Doxorubicin	?45mg/m 2/ day medicine group (4 cycles)	Vein	????D 1

ⅲ) people such as C.A.Linker (Blood 1993; 81:311-318), N.Chao

(Blood 1993 Deng the people; 8:319-323) and people (N. such as A.M.Yeager

Engl.J.Med.1986; 315:145-147) described method:

This method comprises autologous bone marrow transplantation (carrying out in the 0th day):

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D -7-D -2
Busulfan	1mg/kg every day 4 times (totally 16 times)	Oral	????D -7To D -4
				Etoposide	60mg/kg/ days 10 hours infusions	Vein	????D -3

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D -9-D -1
Busulfan	1mg/kg every day 4 times	Oral	????D -9To D -6
				Cyclophosphamide	50mg/kg/ days 1 hour infusion	Vein	????D -5To D -2

ⅳ) in HLA compatibility allogeneic bone marrow transplantation, according to following P.J.Tutscha

(Blood 1987 Deng the people; 70:1382-1388), and F.R.Applebaum

Deng people (Ann.Int.Med.1984; 101:581-588) described method is controlled

Treat:

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D -7-D -1
Busulfan	1mg/kg every day 4 times (totally 16 times)	Oral	????D -7To D -4
				Cyclophosphamide	60mg/kg/ days 1 hour infusion	Vein	????D -3To D -2

2 °/adult chronic leukemia

2.1 chronic myeloid leukemia

In the bone marrow granulocyte phase, can be at people such as C.A.Koller (N.Engl.J.Med.1986; 315:1433-1438) add flavonoid in the described HU-Mith Therapeutic Method:

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5????D 8-D 12????D 15-D 19????D 22-D 26
Hydroxyurea	500mg/ days	Oral	Every day
				Plicamycin	25 μ g/kg/ days 2-4 hour infusions	Vein	Once a day, totally 3 weeks, 3 times/week then

2.2 chronic lymphocytic leukemia

2.2.1 FCG-CLL method

(Leuk.Lymphoma 1991 flavonoid can be added to people such as E.Kimby; 5 (Suppl.) 93-96) and FCGCLL (Blood 1994; 75:1422-1425) in described " pulse chlorambucil " combination treatment:

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5,D -8-D 12, ????D 15-D 22
Chlorambucil or chlorambucil and prednisone	0.1mg/kg/ it 0.4mg/kg/ days per 14 days 75mg/ days	Oral oral	Once/day D 1????D 1-D 3

2.2.2 fludarabine-CdA method

Referring to people such as H.G.Chun (J.Clin.Oncol.1991; 9:175-188), people such as M.J.Keating (Blood 1989; 74:19-25/J.Clin.Oncol.1991; 9:44-49) and people (J.C1in Oncol.1995 such as A.Saven; 13:570-574) described:

	Dosage	Approach	Natural law
				Flavonoid	?200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 8(1 time/month, 6-12 cycle)
Fludarabine or cladribine	???25-30mg/m 2/ day 30 minutes infusion [per 4 weeks, 6-12 cycle] 0.09mg/kg/ days continuous infusion [every 28-35 days 1 cycles, 1-9 cycle (average 4 cycles) altogether]	Cava vein	????D 1-D 5????D 1-D 7

3 °/lymphocytic hyperplasia disease

3.1 Hokdkin disease

Flavonoid can be introduced conventional being used for the treatment of in the polyvoltine Therapeutic Method of Hokdkin disease:

3.1.1 AVDB method

Referring to people such as G.Bonnadonna (Cancer Clin.Trials 1997; 2:217-226) and people (N.Engl.J.Med.1993 such as G.P.Canellos; 327:1478-1484):

	Dosage	Approach	Natural law
				Flavonoid	??200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 3, ????D 15-D 18
Doxorubicin (A)	???25mg/m 2Medicine group	Vein	????D 1,D 15
				Bleomycin (B)	???10U/m 2Medicine group	Vein	????D 1,D 15
Vinblastine (V)	???6mg/m 2Medicine group	Vein	????D 1,D 15
				Dacarbazine (D)	???375mg/m 2Medicine group	Vein	????D 1,D 15

Treatment comprises 6 to 8 cycles, and per 28 days is one-period

3.1.2 MOPP/ABVD method

Referring to people such as G.Bonnadonna (Ann.Intern.Med.1986; 104:739-746) and people (N.Engl.J.Med.1993 such as G.P.Canellos; 327:1478-1484):

Replace the MOPP method with ABVD method (referring to 3.1.1), this treatment comprises 6 cycles, and 28 days is one-period:

The MOPP method	Dosage	Approach	Natural law
				Flavonoid	?200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 3,D 8-D 11And D 14-D 17
Chlormethine (M)	????6mg/m 2Medicine group	Vein	????D 1,D 8
				Vincristine (O)	???1.4mg/m 2Medicine group's (not having maximum)	Vein	????D 1,D 8
General carbazine (P)	????100mg/m 2/ day	Oral	????D 1-D 14
				Prednisone (P)	????40mg/m 2/ day	Oral	????D 1-D 14

3.1.3 Stauford V method

Referring to people such as N.L.Bartlett (J.Clin.Oncol, 1995:13:1080-1088):

	Dosage	Approach	Natural law
				Flavonoid	????200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5, ????D 8-D 12????D 15-D 19????D 22-D 26
Doxorubicin	???????25mg/m 2	Vein	????D 1,D 15
				Vinblastine	??????6mg/m 2Medicine group (as year neighbour 〉=50 years old, 4mg/m in the 3rd cycle 2)	Vein	????D 1,D 15
Chlormethine (M)	?????6mg/m 2The injection of medicine group	Vein	????D 1
				Vincristine	?????1.4mg/m 2Medicine group (maximal dose: 2mg) (as year neighbour 〉=50 years old, 1mg/m in the 3rd cycle 2)	Vein	????D 1,D 22
Bleomycin	?????????5U/m 2	Vein	????D 8,D 22
				Etoposide	????????60mg/m 2	Oral	????D 15,D 16
Prednisone	???????40mg/m 2/ day	Oral	1 time/week (1-9 week)

Treatment comprises 3 cycles, and per 28 days is one-period.

3.1.4 EVA method

According to the described (Proc.Am.Soc.Clin.Oncol.1991 of people such as G.P.Canellos; 10:273):

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5
Etoposide (E)	????100mg/m 22 hours infusions	Oral	????D 1,D 2,D 3
				Vinblastine (V)	????6mg/m 2Medicine group	Vein	????D 1
Doxorubicin	????50mg/m 2Medicine group	Vein	????D 1

Treatment comprises 6 cycles, and 28 days is one-period.

3.1.5 B-CAVe method

According to the described (Ann.Intern.Med.1984 of people such as W.G.Harker; 101:440-446):

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 3
Bleomycin (B)	??????5U/m 2Medicine group	Vein	????D 1
				Lomustine (CCNU)	????100mg/m 2	Oral	????D 1
Doxorubicin (A)	????60mg/m 2Medicine group	Vein	????D 1
				Vinblastine (Ve)	????5mg/m 2Medicine group	Vein	????D 1

Treatment comprises 8 cycles, and per 28 days is one-period.

3.2 non_hodgkin lymphoma

3.2.1 the non_hodgkin lymphoma that grade malignancy is low

ⅰ)-the CVP method

-according to people such as C.M.Bagley (Ann.Intern.Med.1972; 76:227-234) and people such as C.S.Portlock (Blood 1976; 47:747-756) described:

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5
Cyclophosphamide (C)	300-400mg/m 2/ day	Oral	????D 1,D 5
				Vincristine (V)	?1.4mg/m 2Medicine group's (maximum: 2mg)	Vein	????D 1
Prednisone (P)	??100mg/m 2/ day	Oral	????D 1-D 5

Repeating in per 21 days once should the cycle, up to maximum reaction occurring.

ⅱ)-the I-COPA method

-according to people (N.Engl.J.Med.1992 such as RV Smalley; 327:1336-

1341) described:

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5
Cyclophosphamide (C)	??600mg/m 2/ day	Vein	????D 1
				Vincristine (O)	??1.2mg/m 2Medicine group's (maximum: 2mg)	Vein	????D 1
Prednisone (P)	???100mg/m 2/ day	Vein	????D 1-D 5
				Doxorubicin (A)	???50mg/m 2Medicine group	Vein	????D 1
Alpha-interferon (I)	?????6MU/m 2	Intramuscular	????D 22-D 26

Treatment comprises 8 to 10 cycles, 28 days phases weekly.

ⅲ) fludarabine-CdA method

-(Blood 1994 according to people such as P.Solol-Celigny; 84 (Supp.1):

383a), people such as H.Hoeschster (Blood 1994:84 (Supp.1):

564a, and A.C.Kay (J.Clin.Oncol.1992; 10:371-377)

Described:

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 7
Fludarabine or fludarabine and cyclophosphamide or cladribine	???25mg/m 2/ day 0.5 hour infusion 20mg/m 2/ day 600-1000mg/m 2/ day 0.1mg/m 2/ day 24 hours infusions	The cava vein cava vein	????D 1-D 5????D 1-D 5????D 1????D 1-D 7

When using fludarabine, per 28 days repeat one-period; As use cladribine to repeat one-period in then per 35 days.

3.2.2 the non_hodgkin lymphoma of medium grade malignancy

ⅰ)-CHOP or CNOP method

-(Cancer 1976 according to people such as E.M.McKelvey; 38:1484-1493),

People such as J.O.Armitage (J.Clin.Oncol.1984; 2:898-902),

People such as S.Paulovsky (Ann.Oncol.1992; 3:205-209) described:

	Dosage	Approach	Natural law
				Flavonoid	??200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5
Cyclophosphamide (C)	????750mg/m 2/ day	Vein	????D 1
				Doxorubicin (H)	????50mg/m 2Medicine group	Vein	????D 1
Vincristine (O)	????1.4mg/m 2Medicine group's (maximum: 2mg)	Vein	????D 1
				Prednisone (P)	????100mg/m 2/ day (every day 1 time)	Oral	????D 1-D 5

The CHOP method

Available mitoxantrone (N) replaces (the CNOP method) doxorubicin, to treat the patient's (dosage: 12mg/m more than 60 years old ², weekly aspire to the injection of the 1st day vein medicine group).

Use the treatment of CHOP or CNOP method to comprise 6-8 cycle, per 21 days one-periods.

ⅱ)-the MACOP-B method

-according to people such as P.Klimo (Ann.Intern.Med.1985; 102:596-602) and people (J.Clin.Oncol.1994 such as I.A.Cooper; 12:769-778) described.

	Dosage	Approach	Natural law
				Flavonoid	??200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	D 1-D 5,D 8-D 12D 15-D 22,D 29-D 33D 43-D 47,D 57-D 61, D 71-D 75
Methotrexate (M)	????100mg/m 2Medicine group is 300mg/m then 24 hours infusions	Vein	D 8,D 36,D 64
				Folinic acid	15mg4 time/day	Oral	D 9,D 37,D 65
Doxorubicin (A)	????50mg/m 2Medicine group	Vein	D 1,D 15,D 29,D 43,D 57,D 71
				Cycli phosphate amine (C)	????350mg/m 2Medicine group	Vein	D 1,D 5,D 29,D 43,D 57,D 71
Vincristine (O)	????1.4mg/m 2Medicine group's (maximum: 2mg)	Vein	D 8,D 22,D 36,D 50,D 64,D 7 8
				Prednisone (P)	75mg/ days	Oral	Every day 1 time, totally 12 weeks
Bleomycin (B)	????10U/m 2Medicine group	Vein	D 22,D 50,D 78

This Therapeutic Method carried out for 12 weeks, was equivalent to 1 cycle.

ⅲ)-the VACOP-B method

According to people such as J.M.Connors (Proc.Am.Soc.Clin.Oncol.1990; 9:254) described:

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	D 1-D 5,D 8-D 12D 15-D 22,D 29-D 34D 43-D 47,D 57-D 61, D 71-D 75
Etoposide (V)	?????50mg/m 2	Vein	D 15,D 43,D 71
				Etoposide	????100mg/m 2	Oral	D 16,D 17,D 44,D 45,D 72,D ????????? 73
Doxorubicin (A)	??50mg/m 2Medicine group	Vein	D 1,D 15,D 29,D 43,D 57,D 7 ???????????????1
				Cycli phosphate amine (C)	???350mg/m 2/ day medicine group	Vein	D 8,D 22,D 36,D 50,D 64,D 7 ??????????????????8
Vincristine (O)	???1.2mg/m 2Medicine group	Vein	D 8,D 22,D 36,D 50,D 64,D 7 ?????????????????8
				Prednisone (P)	????45mg/m 2/ day	Oral	Every day 1 time, totally 1 week, 4 times/day then, totally 11 weeks

Phase continued for 12 weeks weekly.

ⅳ)-the m-BACOD/M-BACOD method

-according to people such as M.A.Shipp (Ann.Int.Med.1986; 140:757-765) and people (J.Clin.Oncol.1993 such as A.T.Skarin; 1:91-98) described.

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5,D 8-D 12????D 15-D 19
Methotrexate (m) or (M)	????200mg/m 24 hours infusion 3000mg/m 24 hours infusions	Cava vein	????D 8,D 15Or D 15
				Folinic acid	?10mg/m 24 times/day (totally 6 doses)	Oral	????D 9,D 16Or D 16
Bleomycin (B)	????4U/m 2Medicine group	Vein	????D 1
				Doxorubicin (A)	???45mg/m 2Medicine group	Vein	????D 1
Cyclophosphamide (C)	???600mg/m 2Medicine group	Vein	????D 1
				Vincristine (O)	????1mg/m 2Medicine group	Vein	????D 1
Dexamethasone (D)	????6mg/m 2/ day	Oral	????D 3-D 5

Treatment comprises 10 cycles, and per 21 days is one-period.

ⅴ)-the ProMACE/CytaBOM method

-according to people such as D.L.Longo (J.Clin.Oncol.1991; 9:25-38) described.

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5,D 8-D 12
Cyclophosphamide (C)	???650mg/m 20.5 hour infusion	Vein	????D 1
				Doxorubicin (A)	???25mg/m 2Medicine group	Vein	????D 1
Etoposide	????120mg/m 21 hour infusion	Vein	????D 1
				Prednisone (P)	60mg/ days	Oral	????D 1,D 14
Cytosine arabinoside	??300mg/m 2Medicine group	Vein	????D 8
				Bleomycin (B)	???5U/m 2Medicine group	Vein	????D 8
Vincristine (O)	?1.4mg/m 2Medicine group	Vein	????D 8
				Methotrexate	?120mg/m 2Medicine group	Vein	????D 8
Folinic acid	25mg/m 24 times/day (totally 4 doses)	Oral	????D 9

Treatment comprised for 6 to 8 cycles, and per 14 days is one-period.

3.2.3 non_hodgkin lymphoma low or the moderate grade malignancy

ⅰ)-ESHAP treatment method

-under recurrence and first line treatment failure scenarios, use people (J.Clin.Oncol.1994 such as W.S.Velasques; 12:1169-1176) described this method.

	Dosage	Approach	Natural law
				Flavonoid	????200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5
Etoposide (E)	????40mg/m 22 hours infusions	Vein	????D 1-D 4
				Methyllprednisolone (S)	500mg/ days 15 minutes infusions	Vein	????D 1,D 4
Cytosine arabinoside (HA)	????2000mg/m 23 hours infusions	Vein	????D 5
				Cisplatin (P)	????25mg/m 2/ day 24 hours continuous infusions of medicine group	Vein	????D 1-D 4

Treatment comprised for 6 cycles, and per 28 days is one-period.

ⅱ)-MINE treatment method

-under the situation of recurrence process and first line treatment failure, use people (Semin, Oncol.1990 such as F.Cabanillas; 17 (Suppl.10): 28:33) described should the treatment:

	Dosage	Approach	Natural law
				Flavonoid	??200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5
Ifosfamide (I)	????1330mg/m 21 hour infusion	Vein	????D 1-D 3
				Mesna (M)	????1330mg/m 2The ifosfamide infusion, 4-8 hour is 266mg/m behind every dose of infusion 2The injection of medicine group	Vein	????D 1-D 3
Mitoxantrone (M)	??????8mg/m 215 minutes infusions	Vein	????D 1
				Etoposide (E)	????65mg/m 2/ day 1 hour infusion	Vein	????D 1-D 3

This treatment cycle repeated once in per 21 days.

3.3 non_hodgkin lymphoma: Burkitt lymphoma, minicell lymphoma, lymphoblast lymphoma

3.3.1 Magrath method

In the Magrath method, share flavonoid according to following program:

ⅰ)-cycle 1

-(Blood 1984 according to people such as I.T.Magrath; 63:1102-1111) institute

State:

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5????D 8-D 12
Cytosine arabinoside	?????30mg/m 2	Intrathecal injection	????D 1,D 2,D 3,D 7
				Cyclophosphamide	???1200mg/m 2Medicine group	Vein	????D 1
Methotrexate	????12.5mg/m 2(maximum 12.5mg)	Intrathecal injection	????D 10
				Methotrexate	????300mg/m 2/ day 1 hour infusion is pressed 60mg/m then 2/ hour, 41 hours infusions	Vein	????D 10-D 11
Folinic acid	????15mg/m 2Medicine group's (continuous 8 doses)	Vein	The methotrexate that comes into operation begins beginning in back 42 hours

ⅱ)-cycle 2-15

-described according to people such as I.T.Magrath (1984):

	Dosage	Approach	Natural law
				Flavonoid	????200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	D 1-D 3D 10-D 11
Cytosine arabinoside	????45mg/m 2	Intrathecal injection	D 1,D 2(2 and 3 cycle) D 1(4 and 6 cycle)
				Cyclophosphamide (C)	????1200mg/m 2Medicine group	Vein	D 1
Doxorubicin	????40mg/m 2Medicine group	Vein	D 1
				Vincristine	????1.4mg/m 2Medicine group (maximum 2mg)	Vein	D 1
Methotrexate	????12.5mg/m 2(maximum: 12.5mg)	Intrathecal injection	D 3,D 10(2 and 3 cycle) D 10(4,5,6 cycle)
				Methotrexate	????300mg/m 21 hour infusion, 60mg/m then 241 hours continuous infusions	Vein	D 10,D 11(2 and 6 cycle) D 14,D 15(7-15 cycle)
Folinic acid	????15mg/m 2Medicine group 4 times/day (continuous 8 doses)	Vein	With methotrexate for treatment beginning in the 42nd hour

Treatment comprises 14 cycles, and per 28 days is one-period.

3.4 Walden Si Telun macroglobulinemia

3.4.1 CVP method

(Blood 1994 according to people such as M.A.Dimopoulous; 83:1452-1459) people such as C.S.Portlock (Blood 1976; 47:747-756) described CVP method treatment:

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5
Cyclophosphamide (C)	300-400mg/m 2/ day	Oral	????D 1-D 5
				Vincristine (V)	1.4mg/m 2/ day medicine group (maximum: 2mg)	Vein	????D 1
Prednisone (P)	????100mg/m 2/ day	Oral	????D 1-D 5

Treatment continuation in indefinite duration (per 21 days is one-period).

3.4.2 fludarabine-CdA method

(Blood 1990 according to people such as H.M.Kantarjian; 75:1928-1931) and people (Ann.Intern.Med.1993 such as M.A.Dinopoulous; 118:195-198) described:

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5
Fludarabine	????25-30mg/m 20.5 hour infusion	Vein	????D 1-D 5

Perhaps

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 7
Cladribine (CdA)	??0.09mg/m 2/ day continuous infusion	Vein	????D 1-D 7

Treatment comprises 6 to 12 cycles of 28 days at interval when using fludarabine, comprises 2 cycles of 28 days at interval when using cladribine.

3.5 multiple myeloma

3.5.1 MP method

(JAMA 1969 according to people such as R.Alexanian; 208:1680-1685), people such as A.Belch (Br.J.Cancer 1988; 57:94-99) and people (N.Engl.J.Med.1990 such as F.Mandelli; 322:1430-1434) described:

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5
Melphalan (M)	0.25mg/kg/ my god	Oral	????D 1-D 4
				Prednisone (P)	100mg/ days	Oral	????D 1-D 4

Perhaps

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5
Melphalan (M)	???9mg/mg 2/ day	Oral	????D 1-D 4
				Prednisone (P)	100mg/ days	Oral	????D 1-D 4

Treatment comprises at least 12 cycles, and every 4-6 week is one-period.

3.5.2 VAD method

According to people such as B.Barlogie (N.Engl.J.Med.1984; 310:1353-1356) described:

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5
Vincristine (V)	0.4mg/ it 24 hours continuous infusions	Vein	????D 1-D 4
				Many gentle mycins (A)	????9mg/m 2/ day 24 hours continuous infusions	Vein	????D 1-D 4
Dexamethasone (D)	40mg/ days	Vein	????D 1-D 4,D 9-D 12, ????D 17-D 20

3.5.3 MP-interferon-alpha method

(Blood 1993 according to people such as O.Osterborg; 81:1428-1434) described:

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5
Melphalan (M)	0.25mg/kg/ my god	Oral	????D 1-D 4
				Prednisone (P)	2mg/kg/ days	Oral	????D 1-D 4
Interferon-alpha	????7MU/m 2/ day	Subcutaneous	D 1-D 5And D 22-D 26

Treatment comprises and unrestrictedly repeats this cycle that per 42 days is one-period.

3.5.4 VCAP or VBAD method

According to people such as S.E.Salmon (J.Clin.Oncol.1983; 1:453-461):

The VCAP method:

	Dosage	Approach	Natural law
				Flavonoid	200-2000mg/m 2/ sky or 5-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5
Vincristine (V)	????1mg/m 2Medicine group's (maximum: 1.5mg)	Vein	????D 1
				Doxorubicin (A)	????30mg/m 2Medicine group	Vein	????D 1
Prednisone (P)	????60mg/m 2/ day	Oral	????D 1-D 4
				Cyclophosphamide (C)	????125mg/m 2	Oral	????D 1-D 4

The VBAP method: with carmustine alternate collar phosphamide, all the other medicines are the same:

	Dosage	Approach	Natural law
				Carmustine	????30mg/m 21 hour infusion	Vein	????D 1

C. pediatric tumor one pediatric oncology

In order to improve antitumous effect, reduce simultaneously because of raising and mobilize the clone that the effect of paying that effect caused of cell takes place, and reduce dosage, also can in the polyvoltine Therapeutic Method for the treatment of pediatric tumors, add flavonoid.1 °/Ewing sarcoma/the former ectoderm tumor of going crazy

Flavonoid can be incorporated into VCR-Doxo-CY-IfOS-Mesna-E method (E.D.Bergert etc., J.Clin.Oncol.1990; 8:1514-1524; W.H.Meyer etc., J.Clin.Oncol.1992; 10:1737-1742):

	Dosage	Approach	Natural law
				Flavonoid	100-200mg/m 2/ sky or 2-50mg/kg/ days 1 hour infusion	Vein	D 1-D 5And D 22-D 27And D 43-D 48And D 63-D 68
Vincristine	?2mg/m 2Medicine group (maximal dose=2mg)	Vein	??D 1,D 8,D 15,D 43
				Doxorubicin	?30mg/m 2/ day 24 hours infusions	Vein	????D 1-D 3, ????D 43-D 45
Cyclophosphamide	??2.2g/m 20.5 hour infusion	Vein	????D 1,D 43
				Ifosfamide	?180mg/m 2/ day 1 hour infusion	Vein	????D 22-D 26????D 63-D 67
Mesna	????360mg/m 215 minutes infusions, per 3 hours 5 times	Vein	Use with cyclophosphamide and ifosfamide
				Etoposide	????100mg/m 21 hour infusion	Vein	????D 22-D 26????D 63-D 67

According to the initial seriousness and the reaction size of sarcoma, treatment comprises 6-10 cycle.2 °/children acute lymphoblast leukemia, 2.1 induction period chemotherapies (1-30 days)

Method (P.S.Gaynon etc., J.Clin.Oncol., 1993 of recommending; 11:2234-2242; J.Pullen etc., J.Clin.Oncol.1993; 11:2234-2242; J.Pullen etc., J.Clin.Oncol.1993; 11:839-849; V.J.Land etc., J.Clin.Oncol.1994; Can add flavonoid 12:1939-1945):

	Dosage	Approach	Natural law
				Flavonoid	100-200mg/m 2/ sky or 2-50mg/kg/ days 1 hour infusion	Vein	D 1-D 5,D 8-D 11,D 15-D 18????D 22-D 27
Vincristine	?1.5mg/m 2Medicine group (maximal dose=2mg)	Vein	????D 1,D 8,D 15,D 22
				The altheine enzyme	??6000IU/m 2	Intramuscular	3 times/week, totally 3 weeks
Prednisone	???60mg/m 23 doses/day	Oral	???????D 1To D 28
				Doxorubicin	?25mg/m 2/ day 15 minutes infusions	Vein	????D 1,D 8,D 15And D 22
Methotrexate	Decide according to the age	Intrathecal injection	???????D 15,D 28
				Cytosine arabinoside	Decide according to the age	Intrathecal injection	?????????D 1

According to the bone marrow assay, entered consolidation in the 28th day that treats.2.2 consolidate/keep chemotherapy

Keeping treatment (P.S.Gaynon etc., J.Clin.Oncol.1993 by following program; 11:2234-2242; J.Pullen etc., J.Clin.Oncol.1993; 11:839-849; V.J.Land etc., J.Clin.Oncol.1994; Introduce flavonoid 12:1939-1945):

	Dosage	Approach	Natural law
				Flavonoid	100-200mg/m 2/ sky or 2-50mg/kg/ days 1 hour infusion	Vein	D 1-D 5,D 15-D 20And D 94-D 99,D 101- ??D 106, ??D 108-D 113,D 122-D 127
Cyclophosphamide	????100mg/m 20.5 hour infusion	Vein	????D 1,D 15,D 122
				The altheine enzyme	?????600U/m 2	Intramuscular	Between the 97th and 122 day 3 times weekly
Cytosine arabinoside	???75mg/m 2/ day 15 minutes infusions	Vein/subcutaneous	2nd, beginning in 9,16,23,123,1 days is continuous 4 days
				Doxorubicin	???25mg/m 2/ day 15 minutes infusions	Vein	????D 94,D 101,D 108
Purinethol	???60mg/m 2/ day	Oral	1-96, extremely treatment end in 143 days
				Methotrexate	???20mg/m 2/ day	Oral	Between the 36th to 72 day, and weekly between extremely treatment finished in the 143rd day
Prednisone	???40mg/m 2/ day (divide every day and take for 3 times)	Oral	The 143rd day to treatment finish every month continuous 5 days
				Thioguanine	???60mg/m 2/ day	Oral	????D 122-D 135
Vincristine	??1.5mg/m 2Medicine group (maximal dose=2mg)	Vein	94th, 101,108 days, extremely treated in the 143rd day then and finish every month once
				Methotrexate	Decide according to the age	Intrathecal injection	1st, 8,15,22,123,130 days, extremely treated in the 143rd day then and finish per 3 months once

3 °/children acute myeloid leukemia

Inducing and consolidating/keeping and add flavonoid in the Therapeutic Method according to follow procedure: 3.1 induction period chemotherapies

According to people such as Y.Ravindranath (J.Clin.Oncol.1991; 9:572-580), people (J.Clin.Oncol.1994 such as M.E.Nesbit; 12:127-135) and people (J.Clin.Oncol.1994 such as R.J.Wells; 12:2367-2377) described method:

	Dosage	Approach	Natural law
				Flavonoid	100-200mg/m 2/ sky or 2-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5,D 10-D 13
Cytosine arabinoside	Decide according to the age	Intrathecal injection	????D 1
				Many gentle making a gesture of measuring	20mg/m 2/ day 24 hours infusions	Vein	????D 1-D 4,D 10-D 13
Cytosine arabinoside	200mg/m 2/ day 24 hours infusions	Vein	????D 1-D 4,D 10-D 13
				The mercapto guanine	100mg/m 2Divide 2 doses to take/day an every day	Oral	????D 1-D 4,D 10-D 13
Etoposide	100mg/m 2/ day 24 hours infusions	Vein	????D 1-D 4,D 10-D 13
				Dexamethasone	6mg/m 2Divide 3 doses every day	Vein/oral	????D 1-D 4,D 10-D 13

Repeated this cycle from the 28th day.3.2 consolidate/keep chemotherapy

According to people such as Y.Ravidranath (J.Clin.Oncol.1991; 9:572-580; People such as M.E.Nesbit (J.Clin.Oncol.1994; 12:127-135) and people (J.Clin.Oncol.1994 such as R.J.Wells; 12:2367-2377) described method:

	Dosage	Approach	Natural law
				Cytosine arabinoside	Decide according to the age	Intrathecal injection	????D 1,D 28,D 56
Flavonoid	?100-200mg/m 2/ sky or 2-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5,D 8-D 13????D 28-D 33,D 56-D 61????D 89-D 94
				Cytosine arabinoside	????3000mg/m 2Infusion was 3 hours in per 12 hours	Vein	????D 1-D 2And D 8-D 9
The altheine enzyme	????6000IU/m 2Behind the cytosine arabinoside 3 hours	Intramuscular	????D 2,D 9
				Vincristine	????1.5/m 2Medicine group (maximal dose=2mg)	Vein	????D 28,D 56
Thioguanine	????75mg/m 2/ day	Oral	????D 28-D 84
				Cytosine arabinoside	??75mg/m 2/ day medicine group	Vein	????D 28-D 31,D 56-D 59
Cyclophosphamide	????75mg/m 2/ day 0.5 hour infusion	Vein	????D 28-D 31,D 56-D 59
				Cytosine arabinoside	??25mg/m 2/ day medicine group	Subcutaneous/vein	????D 89-D 93
Thioguanine	????50mg/m 2/ day	Oral	????D 89-D 93
				Etoposide	???100mg/m 2/ day 1 hour infusion	Vein	????D 89,D 92
Dexamethasone	????2mg/m 2/ day	Oral	????D 89-D 92
				Doxorubicin	?????30mg/m 215 minutes infusions	Vein	????D 89

4 °/child Hokdkin disease

(Cancer 1990 flavonoid to be joined people such as EA Gehan; 65:1429-1437), people (J.Clin.Oncol.1994 such as SP Hunger; 12:2160-2166) and people (J.Clin.Oncol.1993 such as MM Hudson; 11:100-108) in the described Therapeutic Method:

	Dosage	Approach	Natural law
				Flavonoid	100-200mg/m 2/ sky or 2-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5And D 8-D 12
Chlormethine (M)	???6mg/m 2Medicine group	Vein	????D 1,D 8
				Vincristine (O)	??1.5mg/m 2Medicine group (maximum 2mg)	Vein	????D 1,D 8
Procarbazine (P)	??100mg/m 2/ day	Oral	????D 1-D 14
				Prednisone (P)	??40mg/m 2/ day (being divided into three doses every day)	Oral	????D 1-D 14
Doxorubicin (A)	??25mg/m 2/ day 15 minutes infusions	Vein	????D 29,D -43
				Dacca mycin (B)	???10U/m 215 minutes infusions	Vein	????D 29,D 43
Vinblastine (V)	??6mg/m 2Medicine group (maximum 2mg)	Vein	????D 29,D 43
				Dacarbazine (D)	???375mg/m 215 minutes infusions	Vein	????D 29,D 43

This cycle should repeat 6 times, and in each 8 weeks, treatment comprises 6 cycles.

If carry out the consubstantiality bone marrow transplantation, can use people (Blood1993 such as R.Chopra by following program; 81:1137-1145), people (J.Clin.Oncol.1990 such as C.Wheeler; 8:648-656) and people (J.Clin.Oncol.1990 such as R.J.Jones; 8:527-537) described CVB method (autologous bons marrow transplantation is implanted in the 0th day to carry out):

	Dosage	Approach	Natural law
				Flavonoid	????100-200mg/m 2/ sky or 2-50mg/kg/ days 1 hour infusion	Vein	????D -7,D -1
Cyclophosphamide	????1800mg/m 2/ day 2 times 1 hour infusion	Vein	????D -7,D -6????D -5,D -4
				Carmustine (BCNU)	????112mg/m 2/ day 0.5 hour infusion	Vein	????D -7,D -6????D -5,D -4
Etoposide	????500mg/m 2/ day 2 times 1 hour infusion	Vein	????D -7,D -6????D -5,D -4

5 °/child lymphoblast lymphoma

Flavonoid also can with induce chemical method (A.T.Meadows etc., J.Clin.Oncol.1989; 7:92-99 and C.Patte etc., Med.Ped.Oncol.1992; 20:105-113, and A.Reiter etc., J.Clin.Oncol.1995; 13:359-372) and keep chemotherapy and share: 5.1 induce chemotherapy

	Dosage	Approach	Natural law
				Flavonoid	????????100-200mg/m 2/ sky or 2-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5, ????D 17-D 22,D 24-D 29
Cyclophosphamide	??????????????1200mg/m 20.5 infusion in hour	Vein	????D 1
				Cytosine arabinoside	Decide according to the age	Intrathecal injection	????D 1
Vincristine	??1.5mg/m 2Medicine group (maximum 2mg)	Vein	????D 3,D 10,D 17,D 24
				Prednisone	?60mg/m 2/ day, divide three doses every day	Oral	????D 3-D 2
Doxorubicin	????60mg/m 2, 15 minutes infusions	Vein	????D 17
				The altheine enzyme	6000U/m 2/ day, 15 minutes infusions	Intramuscular	????D 17-D 353 times/week
Methotrexate	Decide according to the age	In the sheath	????D 17,D -31

5.2 the chemotherapy of keeping

According to follow procedure:

	Dosage	Approach	Natural law
				Flavonoid	100-200mg/m 2/ sky or 2-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5, ????D 15-D 20.D 29-D 34
Cyclophosphamide	1000mg/m 20.5 infusion in hour	Vein	????D 1
				Vincristine	1.5mg/m 2Medicine group (maximum 2mg)	Oral	????D 1,D 5(2-10 cycle)
Methotrexate	300mg/m 2/ day (15 clock infusion 60%, 4 hour in infusion 40%)	Vein	????D 15
				Folinic acid	10mg/m 2/ per 4 hours	Oral	????D 16
Doxorubicin	30mg/m 20.5 hour infusion	Vein	????D 29
				Methotrexate	Decide according to the age	Intrathecal injection	????D 1,D 8,D 15(the 1st cycle), 1 time/month then (2-10 cycle)

Treatment comprises 10 cycles.

6 °/child neuroblastoma

The Doxo-E-Cy-Pt polyvoltine therapy of recommending is derived from people such as R.P.Castleberry (J.Clin.Oncol.1992; 10:1299-1304), people (J.Clin.Oncol.1993 such as A.Garaventa; 11:1770-1779) and people (J.Clin.Oncol.1992 such as D.C.West; 11:84-90) described method:

	Dosage	Approach	Natural law
				Flavonoid	100-200mg/m 2/ sky or 2-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5????D 28-D 35, ????D 58-D 65
Doxorubicin	????25mg/m 2/ day 15 minutes infusions	Vein	????D 2,D 30,D 58
				Yi Tuo moors glycosides	??????100mg/m 21 hour infusion	Oral/the per nasal stomach	D 2,D 5,D 30,D 33,D 58,D 61
Cyclophosphamide	?????1000mg/m 20.5 hour infusion	Vein	D 3,D 4,D 31,D 32,D 59,D 60
				Cisplatin	???????60mg/m 26 hours infusions	Vein	????D 1,D 28,D 56

9 all post-evaluation therapeutic responses are so that really further Therapeutic Method: surgical excision, radiotherapy or new chemotherapy.7 °/bone in children sarcoma

At people such as M.Hudson (J.Clin.Oncol.1990; 8:1988-1997), P.A.Meyers (J.Clin.Oncol.1992; 10:5-15) and people (J.Clin.Oncol.1992 such as V.H.C.Bramwell; 10:1579-1591) add flavonoid in the described Doxo-Pt-Mtx-Lcv method:

	Dosage	Approach	Natural law
				Flavonoid	100-200mg/m 2/ sky or 2-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5, ????D 21-D 26. ????D 28-D 33
Doxorubicin	???25mg/m 2/ day 24 hours infusions	Vein	????D 1-D 3
				Cisplatin	?120mg/m 26 hours infusions	Vein	????D 1
Methotrexate	12mg/m 2/ day 1 hour infusion	Vein	????D 21,D 28
				Folinic acid	??100mg/m 2/ per 6 hours	Oral	????D 22,D 29

8 °/child rhabdomyosarcoma

Can by following program the Vcr-Dact-CY-Mesna method (H.Maurer etc., Cancer 1993; 71:1904-1922 and L.R.Mandell etc., Oncology 1993; Add the venoclysis flavonoid 7:71-83):

	Dosage	Approach	Natural law
				Flavonoid	100-200mg/m 2/ sky or 2-50mg/kg/ days 1 hour infusion	Vein	????D 1-D 5,D 8-D 12, ???D 22-D 27,D 43-D 47
Vincristine	??1.5mg/m 2/ day medicine group, maximum 2mg	Vein	D 1,D 8,D 15,D 22,D 29,D 36????,D 43,D 50,D 57
				Actinomycin D	0.015mg/kg medicine group (maximal dose 0.5mg every day)	Vein	????????D 1-D 5, ????D 22-D 27,D 43-D 47
Cyclophosphamide	??2.2mg/m 21 hour infusion	Vein	???????D 1,D 22,D 43
				Mesna	???360mg/m 2Infusion was 1 hour in per 3 hours, totally 5 doses	Vein	???????D 1,D 22,D 43

Ying Zaidi estimated therapeutic effect when 9 weeks, treatment finished, to determine next step measure that should adopt (surgical operation, radiotherapy, continuation chemotherapy).9 °/child wilms' tumor

(as GJ D ' Angio etc., Cancer 1989 in following Vcr-Dact method; 64:349-360 and DM Green etc., J.Clin.Oncol.1993; 11:91-95 is described) in add and use flavonoid:

	Dosage	Approach	Natural law
				Flavonoid	????100-200mg/m 2/ sky or 2-50mg/kg/ days 1 hour infusion	Vein	??D 1-D 5,D 8-D 12Injection weekly then
Vincristine	????2mg/m 2Medicine group's (maximal dose: 2mg)	Vein	??????D 7Injection weekly then
				Actinomycin D	0.045mg/kg (the 1.35mg/m of P≤30kg) of medicine group 2((the maximal dose: 3mg) of P＞30kg)	Vein	D 1, per then 3 weeks 1 time

This method begins after surgical discectomy.

According to people such as A.Garaventar (Med.Pediatr.Oncol.1994; 22:11-14) described when carrying out autologous bone marrow transplantation, can be modified as follows the E-Thio-Cy method:

	Dosage	Approach	Natural law
				Flavonoid	100-200mg/m 2/ sky or 2-50mg/kg/ days 1 hour infusion	Vein	????D -8-D -1
Etoposide	????1800mg/m 224 hours infusions	Vein	????D -8
				Tespamin	????300mg/m 2/ day 2 hours infusions	Vein	????D -7,D -6,D -5
Cyclophosphamide	50mg/kg/ days 1 hour infusion	Vein	????D -4,D -3,D -2,D -1

Bone marrow transplantation was carried out at the 0th day.

Claims (10)

1. the propagation to clone's generation cell in the tumor has active compositions, and it comprises the flavonoid for the treatment of effective dose.

2. the propagation to clone's generation cell in the tumor has active compositions, and it comprises the chemical compound that is selected from the formula I chemical compound for the treatment of effective dose

Wherein :-R ₁, R ₂, R ₃And R ₄Be selected from H, OH, C independently of one another ₁-C ₄Alkoxyl and-OCOR ₇Group, R ₇Be C ₁-C ₄Alkyl, substituent R ₁, R ₂, R ₃Or R ₄In at least one be not H, and R ₂And R ₃Can form methylene-dioxy ,-R together ₅Be selected from H, OH, C ₁-C ₄Alkoxyl and O-glycosyl group ,-R ₆Be selected from cyclohexyl, phenyl and quilt are selected from H, OH and C ₁-C ₄Alkoxyl replaces 1 to 3 time phenyl group ,-and Two keys of representative or strand.

3. according to the compositions of claim 2, wherein flavonoid is a flavone.

4. according to the compositions of claim 2, wherein flavonoid is a Quercetin.

5. flavonoid is used for disturbing between with at least a cytotoxic agent treatment tumor stage the tumor clone that application in the medicine that cell generates takes place in preparation.

6. the chemical compound that is selected from the chemical compound of following formula is used for disturbing between with at least a cytotoxic agent treatment tumor stage the tumor clone that application in the medicine that cell generates takes place in preparation,

Wherein :-R ₁, R ₂, R ₃And R ₄Be selected from H, OH, C independently of one another ₁-C ₄Alkoxyl and-OCOR ₇Group, R ₇Be C ₁-C ₄Alkyl, substituent R ₁, R ₂, R ₃Or R ₄In at least one be not H, and R ₂And R ₃Can form methylene-dioxy ,-R together ₅Be selected from H, OH, C ₁-C ₄Alkoxyl and O-glycosyl group ,-R ₆Be selected from cyclohexyl, phenyl and quilt are selected from H, OH and C ₁-C ₄Alkoxyl replaces 1 to 3 time phenyl group ,-and

Two keys of representative or strand.

7. according to the application of claim 6, wherein flavonoid is a flavone.

8. according to the application of claim 6, wherein flavonoid is a Quercetin.

9. with the method for at least a cytotoxic agent chemotherapy patient tumor, it is included in the flavonoid with the treatment effective dose that comes into operation during the cytotoxic agent treatment.

10. according to the method for claim 9, wherein when chemotherapy begins and the flavonoid that comes into operation when beginning of chemotherapeutical each cycle.