CN102178672A - Medicinal composition for treating esophageal cancer or nasopharyngeal darcinoma, and application, kit and packaging piece - Google Patents

Abstract

The invention relates to a medicinal composition for treating esophageal cancer or nasopharyngeal darcinoma, and application, a kit and a packaging piece. The medicinal composition, the kit and the packaging piece comprise Lobaplatin with treatment effective dose and Docetaxel with treatment effective dose which serve as a combined preparation to be used simultaneously, separately and sequentially. The medicinal composition, the kit and the packaging piece can achieve excellent curative effect and have small toxic or side effect when used for treating esophageal cancer or nasopharyngeal darcinoma.

Description

The treatment esophageal carcinoma or nasopharyngeal carcinoma pharmaceutical composition and application, test kit and package

Technical field

The present invention relates to a kind of cancer therapy drug, relate in particular to a kind of treatment esophageal carcinoma or nasopharyngeal carcinoma pharmaceutical composition and application thereof.

Background technology

China is one of country that esophageal carcinoma sickness rate and case fatality rate are the highest in the world.The esophageal carcinoma is geographic common cancers such as China North China, northern Suzhou and Chuan Bei, particularity because of its anatomical structure: thin-walled, polyphone organ, be close to the spinal column walking, discrete mucosa multiple spot origin, multiple focus has abundant lymphatic vessel web frame etc. under the mucous membrane of esophagus, when the patient seeks medical advice, there is 2/3 patient to be in middle and advanced stage, do not have the operation indication, even lost the chance of radiotherapy.Chemotherapy can reach the purpose of palliative treatment as one of means of Comprehensive Treatment.Even about 1/3～1/2 patient with esophageal carcinoma has been accepted operation and has been aided with treatment such as radiation and chemotherapy, 3 years survival rates also only are 30%-35% after the Resection of Esophageal Carcinoma, and 5 years survival rates are less than 20% still.

In recent years, along with new cancer therapy drug continues to bring out, for the late esophagus cancer patient has brought new hope.Up to now, the medicine of the treatment late esophagus cancer of still readily good therapeutic effect satisfaction.

On the other hand, nasopharyngeal carcinoma is one of higher malignant tumor of south east asia sickness rate such as China south and Singapore, Malaysia, China is the highest country of nasopharyngeal carcinoma sickness rate in the world, ground such as the Guangdong of China, Guangxi, Fujian, Hunan, Hubei are multiple district, age of onset is mostly in 40-60 year, also have teenager to suffer from the patient, the male is more to be seen, its 5 annual survival rate all is lower than 50%.The cause of disease is relevant with ethnic susceptibility (yellow is ill many than white people), inherited genetic factors and ebv infection etc.Nasopharyngeal carcinoma is the very strong tumor of a kind of invasive, invades DEEP STRUCTURE in early days, and local recurrence and metastasis are nasopharyngeal carcinoma patient major causes of death.

There is a large amount of resourcess for research in China, but the holistic approach of nasopharyngeal carcinoma, treatment level are still lower, therefore carry out large-scale polycentric clinical research in a deep going way, improve therapeutic effect, China's nasopharyngeal carcinoma treatment level and its morbidity are matched, be in prostatitis, the world, a large amount of crowds are benefited, significant.

In the treatment of nasopharyngeal carcinoma, the early stage feasible radical radiation therapy of nasopharyngeal carcinoma, but radiotherapy only is used for the treatment of primary tumo(u)r and regional lymph nodes.Nasopharyngeal carcinoma is the more sensitive tumor of a kind of chemotherapeutic treatment.Up to now, there is not a kind of medicine to the satisfaction of nasopharyngeal carcinoma therapeutic effect.

Summary of the invention

Technical problem solved by the invention is, pharmaceutical composition and application, test kit and the package of a kind of effective treatment late esophagus cancer or nasopharyngeal carcinoma is provided.

A first aspect of the present invention, about the medicine of treatment late esophagus cancer, the inventor has carried out following investigation and research:

(Lobaplatin LBP) is the third generation platinum series antineoplastic medicament that the research and development of German ASTA pharmaceutical factory, Chinese Hainan Chang'an International Pharmaceutical Co., Ltd produce to lobaplatin.The LBP anticancer spectrum is similar to cisplatin, and active anticancer and cisplatin are suitable, and has and cisplatin, carboplatin do not have crossing drug resistant, the significantly reduced distinguishing feature of toxicity.The inventor shows lobaplatin 50mg/m after studying the therapeutic effect of lobaplatin ²Single medicine is 28% to the total effective rate of esophageal squamous cell carcinoma, wherein just controls patient's effective percentage up to 36%.Domestic scholars studies show that LBP associating 5-Fu/CF is 54.9% to the total effective rate of advanced esophageal cancer, wherein just controls patient's effective percentage up to 68.2%; Total effective rate to the postoperative metastasis esophageal carcinoma is 53.1%, wherein just controls patient 63.2%, controls patient 38.5% again; The toxicity of LBP associating 5-Fu/CF significantly lowers than the cisplatin scheme of standard, and toleration and safety are better.The inventor thinks, contains the Combination chemotherapy of LBP, has important clinical value in the esophageal carcinoma treatment late, is worth further studies have shown that.Simultaneously, the inventor notices that (Docetaxel is a kind of semisynthetic Ramulus et folium taxi cuspidatae class medicine DTX) to Docetaxel, can strengthen microtubule polymerization and suppress microtubule depolymerization, thereby destroy the tumor cell mitosis.No matter DTX is single medicine or drug combination, all obtains significant curative effect in the esophageal carcinoma one line and two wires adjuvant chemotherapy, becomes in the esophageal carcinoma chemotherapy one of the most activated medicine.Therefore, the inventor has carried out further investigation back and has found, LBP and DTX is united be used for the treatment of the esophageal carcinoma and can obtain unexpected therapeutic effect.

Thereby about the medicine of the treatment esophageal carcinoma, the inventor provides as next group technical scheme:

(1) a kind of treatment esophageal carcinoma pharmaceutical composition, it contains the lobaplatin of the treatment effective dose that supplies simultaneously, separates or use in order as combination formulations and the Docetaxel of treatment effective dose.

(2) according to the described compositions of technical scheme (1), in weight portion, contain 20-50 part lobaplatin and 65-90 part Docetaxel, preferably contain 20-30 part lobaplatin and 65-75 part Docetaxel, more preferably contain 30 parts of lobaplatin and 75 parts of Docetaxels.

Wherein, above-mentioned composition is when delivering medicine to the patient, and the lobaplatin daily dose is 20-50mg/m ², the Docetaxel daily dose is 65-90mg/m ², preferably lobaplatin is delivered medicine to the patient second day of medication cycle, Docetaxel is delivered medicine to the patient first day of medication cycle, the described medication cycle is 21 days.

(3) a kind of treatment esophageal carcinoma test kit comprises first test kit unit that contains lobaplatin and the second test kit unit that contains Docetaxel.

(4) according to the described test kit of technical scheme (3), the described first test kit unit that contains lobaplatin comprises 20-50mg/m ², preferred 20-30mg/m ², more preferably 30mg/m ²Daily dose/unitary lobaplatin unit, the described second test kit unit that contains Docetaxel comprises 65-90mg/m ², preferred 65-75mg/m ², more preferably 75mg/m ²Daily dose/unitary Docetaxel unit, described daily dose is the quality of active component.

(5) according to technical scheme (3) or (4) described test kit, the described first test kit unit that contains lobaplatin comprises 32.2-80.5mg, preferred 32.2-48.3mg, more preferably 48.3mg daily dose/unitary lobaplatin unit, the described second test kit unit that contains Docetaxel comprises 104.7-144.9mg, preferred 104.7-120.8mg, more preferably 120.8mg daily dose/unitary Docetaxel unit, and described daily dose is the quality of active component.

(6) according to the described test kit of technical scheme (5), the described first test kit unit that contains lobaplatin comprises 1-3 32.2-80.5mg, preferred 32.2-48.3mg, more preferably 48.3mg daily dose/unitary lobaplatin unit, and the described second test kit unit that contains Docetaxel comprises 1-3 104.7-144.9mg, preferably 104.7-120.8mg, more preferably 120.8mg daily dose/unitary Docetaxel unit.

Wherein, in the mentioned reagent box each lobaplatin unit and each Docetaxel unit associations as the one-period medicine that is used for the treatment of patient with esophageal carcinoma.For patient with esophageal carcinoma, daily dose can be adjusted according to weight in patients or body surface area and state of an illness needs.Therefore, when making test kit, can comprise the little lobaplatin unit of some independent packagings in each lobaplatin unit, the lobaplatin total amount in each little lobaplatin unit meets above-mentioned daily dose area requirement; The little Docetaxel unit that can comprise some independent packagings in each Docetaxel unit, the Docetaxel total amount meets the area requirement of above-mentioned daily dose in each little Docetaxel unit.

(7) a kind of package of packing the treatment esophageal carcinoma with medicine comprises packaging space second packaging unit that contains first packaging unit of lobaplatin and contain Docetaxel independent of each other.

(8) according to the described package of technical scheme (7), the described first test kit unit that contains lobaplatin comprises 20-50mg/m ², preferred 20-30mg/m ², more preferably 30mg/m ²Daily dose/unitary lobaplatin unit, the described second test kit unit that contains Docetaxel comprises 65-90mg/m ², preferred 65-75mg/m ², more preferably 75mg/m ²Daily dose/unitary Docetaxel unit, described daily dose is the quality of active component.

(9) according to technical scheme (7) or (8) described package, described first packaging unit that contains lobaplatin comprises 32.2-80.5mg, preferred 32.2-48.3mg, more preferably 48.3mg daily dose/unitary lobaplatin unit, described second packaging unit that contains Docetaxel comprises 104.7-144.9mg, preferred 104.7-120.8mg, more preferably 120.8mg daily dose/unitary Docetaxel unit, and described daily dose is the quality of active component.

(10) according to the described package of technical scheme (9), the described first parcel post unit that contains lobaplatin comprises 1-3 32.2-80.5mg, preferred 32.2-48.3mg, more preferably 48.3mg daily dose/unitary lobaplatin unit, and described second packaging unit that contains Docetaxel comprises 1-3 104.7-144.9mg, preferably 104.7-120.8mg, more preferably 120.8mg daily dose/unitary Docetaxel unit.

Wherein, in the above-mentioned package each lobaplatin unit and each Docetaxel unit associations as the one-period medicine that is used for the treatment of patient with esophageal carcinoma.Wherein, for patient with esophageal carcinoma, daily dose can be adjusted according to weight in patients or body surface area and state of an illness needs.Therefore, when making package, can comprise the little lobaplatin unit of some independent packagings in each lobaplatin unit, the lobaplatin total amount in each little lobaplatin unit meets above-mentioned daily dose area requirement; The little Docetaxel unit that can comprise some independent packagings in each Docetaxel unit, the Docetaxel total amount meets the area requirement of above-mentioned daily dose in each little Docetaxel unit.

(11) according to each described package among each described test kit or the technical scheme 7-10 in technical scheme (3)-(6), also comprise description, stipulate in this description, lobaplatin in the described lobaplatin unit delivers medicine to the patient second day of medication cycle, Docetaxel delivers medicine to the patient first day of medication cycle in the described Docetaxel unit, and the described medication cycle is 21 days.

(12) according to described test kit of technical scheme (11) or package, described lobaplatin and described Docetaxel are ejection preparation; Soft capsule; Or tablet.

(13) being combined in of lobaplatin and Docetaxel prepares the application for the treatment of in the esophageal carcinoma medicine.

(14) according to the described application of technical scheme (13), described lobaplatin and Docetaxel consumption are (20-50)/(65-90) by weight, preferred (20-30)/(65-75).

In the present invention, described lobaplatin and described Docetaxel can be the combinations of any known dosage form when combination is used for the treatment of the esophageal carcinoma, and be preferred, and lobaplatin and Docetaxel are separately with the combined esophageal carcinoma that is used for the treatment of of ejection preparation independently.Adopt lobaplatin and Docetaxel can be the various dosage forms of selling on the market among the present invention.

The preparation method of mentioned reagent box or package is: adopt the material or the container of test kit packing reagent commonly used, with lobaplatin and the Docetaxel pharmaceutical preparation for preparing in commercial or the embodiment of the invention, the above-mentioned daily dose of stipulating according to the present invention carries out packing.When pharmaceutical composition of the present invention, test kit and package are used for the treatment of the esophageal carcinoma, can obtain excellent therapeutic effect, and each toxic and side effects is little.

A second aspect of the present invention, the inventor also finds, lobaplatin and Docetaxel associating can effectively be treated nasopharyngeal carcinoma.Specifically, the medicine inventor about the treatment nasopharyngeal carcinoma has carried out following investigation and research.

The inventor combines the current research data that is published in PubMed, MEDLINE in recent years, wherein two meta-analysises and at least 6 random research results show, advanced NPC patient for the metastasis that occurs together, the platinum class for the basis, select or two medicine combined chemotherapies of Ramulus et folium taxi cuspidatae class can obtain the same curative effect of traditional multiple medicines chemotherapy regimen with strong, and be easier to tolerance.Because one, the significant nephrotoxicity of secondary platinum class, digestive tract reaction, haematics toxicity, and, in clinical use, be restricted the influence of quality of life.

Lobaplatin is a third generation platinum class.The I phase clinical research of lobaplatin shows, clinical research shows that its nephrotoxicity, ototoxicity and neurotoxicity are slight, and the dose-limiting toxicity of this product is a thrombocytopenia, mostly is the WHO2--3 degree, often took place in 7--14 days, and after injection, recover automatically in 3 weeks in the injection back.Leukopenia on average betides after the injection the 19th day, recovers rapidly.Lobaplatin has obvious inhibitory action to some cisplatin Drug resistance human tumor cell line (colon, mammary gland, lung).These researchs show that all lobaplatin has tangible active anticancer, and with cisplatin, carboplatin crossing drug resistant characteristic not.

The II clinical trial phase of lobaplatin shows that the single dose lobaplatin has activity to nasopharyngeal carcinoma, breast carcinoma and kinds of tumors such as small cell lung cancer, ovarian cancer.The II clinical trial phase that carries out in China shows, lobaplatin single therapy nasopharyngeal carcinoma has obvious curative effects, its effective percentage seemingly is better than cisplatin and carboplatin, in view of lobaplatin good prospect in the nasopharyngeal carcinoma treatment, research worker of the present invention is carried out the perspective open clinical research of lobaplatin (LBP) associating Docetaxel (DTX), to inquire into effectiveness and the safety of this scheme in the Comprehensive Treatment of nasopharyngeal carcinoma.

Paclitaxel is the natural materials of a kind of highly effective antineoplastic activity of extracting from Chinese yew genus plants, and its basic structure 10-deacetylation baccatin III (10-DAB) is that first is proved the material with anti-tumor activity in the Ramulus et folium taxi cuspidatae class medicine family.1985.France Rhone-Poulenc Rorer and French national physicism center with 10-DAB as the parent nucleus skeleton, made Docetaxel by semisynthetic method. its cytotoxicity is identical with paclitaxel mechanism. by combining with the cell tubulin, promote the tubulin gathering and form stable microtubule, suppress microtubule depolymerization, finally make microtubule fasolculus form afunction, suppress cell mitogen.Acting on the other drug of cell mitogen phase with Colchicine, vinca or paclitaxel etc. compares.Do not change the bibril strand quantity of microtubule fasolculus with the bonded Docetaxel of microtubule. it suppresses microtubule depolymerization simultaneously, the ability that promotes the microtubule dimer to aggregate into microtubule is paclitaxel 2 times.

Therefore, about the medicine of treatment nasopharyngeal carcinoma, the result that the inventor studies with keen determination provides following technical scheme:

(1) a kind of treatment nasopharyngeal carcinoma pharmaceutical composition, it contains the lobaplatin of the treatment effective dose that supplies simultaneously, separates or use in order as combination formulations and the Docetaxel of treatment effective dose.

(2) according to the described compositions of technical scheme (1), in weight portion, contain 20-50 part lobaplatin and 65-90 part Docetaxel, preferably contain 20-30 part lobaplatin and 65-75 part Docetaxel, more preferably contain 30 parts of lobaplatin and 75 parts of Docetaxels.

Wherein, above-mentioned composition is when delivering medicine to the patient, and the lobaplatin daily dose is 20-50mg/m ², the Docetaxel daily dose is 65-90mg/m ², preferably lobaplatin and Docetaxel all being delivered medicine to the patient at first day of the medication cycle, the described medication cycle is 21 days.

(3) a kind of treatment nasopharyngeal carcinoma test kit comprises first test kit unit that contains lobaplatin and the second test kit unit that contains Docetaxel.

(4) according to the described test kit of technical scheme (3), the described first test kit unit that contains lobaplatin comprises 20-50mg/m ², preferred 20-30mg/m ², more preferably 30mg/m ²Daily dose/unitary lobaplatin unit, the described second test kit unit that contains Docetaxel comprises 65-90mg/m ², preferred 65-75mg/m ², more preferably 75mg/m ²Daily dose/unitary Docetaxel unit, described daily dose is the quality of active component.

(5) according to technical scheme (3) or (4) described test kit, the described first test kit unit that contains lobaplatin comprises 32-80mg, preferred 32-48mg, more preferably 48mg daily dose/unitary lobaplatin unit, the described second test kit unit that contains Docetaxel comprises 104-144mg, preferred 104-120mg, more preferably 120mg daily dose/unitary Docetaxel unit, and described daily dose is the quality of active component.

(6) according to the described test kit of technical scheme (5), the described first test kit unit that contains lobaplatin comprises 1-3 32-80mg, preferred 32-48mg, more preferably 48mg daily dose/unitary lobaplatin unit, and the described second test kit unit that contains Docetaxel comprises 1-3 104-144mg, preferably 104-120mg, more preferably 120mg daily dose/unitary Docetaxel unit.

Wherein, in the mentioned reagent box each lobaplatin unit and each Docetaxel unit associations as the one-period medicine that is used for the treatment of the nasopharyngeal carcinoma patient.For the nasopharyngeal carcinoma patient, daily dose can be adjusted according to weight in patients or body surface area and state of an illness needs.Therefore, when making test kit, can comprise the little lobaplatin unit of some independent packagings in each lobaplatin unit, the lobaplatin total amount in each little lobaplatin unit meets above-mentioned daily dose area requirement; The little Docetaxel unit that can comprise some independent packagings in each Docetaxel unit, the Docetaxel total amount meets the area requirement of above-mentioned daily dose in each little Docetaxel unit.

(7) a kind of package of packing the treatment nasopharyngeal carcinoma with medicine comprises packaging space second packaging unit that contains first packaging unit of lobaplatin and contain Docetaxel independent of each other.

(8) according to the described package of technical scheme (7), the described first test kit unit that contains lobaplatin comprises 20-50mg/m ², preferred 20-30mg/m ², more preferably 30mg/m ²Daily dose/unitary lobaplatin unit, the described second test kit unit that contains Docetaxel comprises 65-90mg/m ², preferred 65-75mg/m ², more preferably 75mg/m ²Daily dose/unitary Docetaxel unit, described daily dose is the quality of active component.

(9) according to technical scheme (7) or (8) described package, described first packaging unit that contains lobaplatin comprises 32-80mg, preferred 32-48mg, more preferably 48mg daily dose/unitary lobaplatin unit, described second packaging unit that contains Docetaxel comprises 104-144mg, preferred 104-120mg, more preferably 120mg daily dose/unitary Docetaxel unit, and described daily dose is the quality of active component.

(10) according to the described package of technical scheme (9), the described first parcel post unit that contains lobaplatin comprises 1-3 32-80mg, preferred 32-48mg, more preferably 48mg daily dose/unitary lobaplatin unit, and described second packaging unit that contains Docetaxel comprises 1-3 104-144mg, preferably 104-120mg, more preferably 120mg daily dose/unitary Docetaxel unit.

Wherein, in the above-mentioned package each lobaplatin unit and each Docetaxel unit associations as the one-period medicine that is used for the treatment of the nasopharyngeal carcinoma patient.Wherein, for the nasopharyngeal carcinoma patient, daily dose can be adjusted according to weight in patients or body surface area and state of an illness needs.Therefore, when making package, can comprise the little lobaplatin unit of some independent packagings in each lobaplatin unit, the lobaplatin total amount in each little lobaplatin unit meets above-mentioned daily dose area requirement; The little Docetaxel unit that can comprise some independent packagings in each Docetaxel unit, the Docetaxel total amount meets the area requirement of above-mentioned daily dose in each little Docetaxel unit.

(11) according to each described package in each described test kit in technical scheme (3)-(6) or technical scheme (7)-(10), also comprise description, stipulate in this description, Docetaxel all delivered medicine to the patient at first day of the medication cycle in lobaplatin in the described lobaplatin unit and the described Docetaxel unit, and the described medication cycle is 21 days.

(12) according to described test kit of technical scheme (11) or package, described lobaplatin and described Docetaxel are ejection preparation; Soft capsule; Or tablet.

(13) being combined in of lobaplatin and Docetaxel prepares the application for the treatment of in the medicine for nasopharyngeal.

(14) according to the described application of technical scheme (13), described lobaplatin and Docetaxel consumption are (20-50)/(65-90) by weight, preferred (20-30)/(65-75).

In the present invention, described lobaplatin and described Docetaxel can be the combinations of any known dosage form when combination is used for the treatment of nasopharyngeal carcinoma, and be preferred, and lobaplatin and Docetaxel are separately with the combined nasopharyngeal carcinoma that is used for the treatment of of ejection preparation independently.Adopt lobaplatin and Docetaxel can be the various dosage forms of selling on the market among the present invention.

The preparation method of mentioned reagent box or package is: adopt the material or the container of test kit packing reagent commonly used, with lobaplatin and the Docetaxel pharmaceutical preparation for preparing in commercial or the embodiment of the invention, the above-mentioned daily dose of stipulating according to the present invention carries out packing.

Pharmaceutical composition of the present invention effect in the treatment of nasopharyngeal carcinoma is remarkable, and safety is good, and toxic and side effects is little, can protect hemopoietic function of bone marrow, and can effectively improve the effect of chemotherapeutic period patients ' life quality.

The specific embodiment

The lobaplatin anti-tumor activity comes from the formation of DNA-medicine adduct, mainly is that the chain of GC and AG is interior crosslinked.Studies show that LBP can influence tumor cell c-myc expression of gene, and the expression of c-myc is relevant with generation, apoptosis and the cell proliferation of tumor.For solid tumors such as the esophageal carcinoma, nasopharyngeal carcinoma, the DNA crosslinked action of LBP is considered to the main mechanism of its antitumor action.Interior and the interchain linkage of platinum class and DNA chain can hinder duplicating and transcription of DNA, thereby disturbs the operation of tumour cell cycle.Proliferating cell nuclear antigen (PCNA) is a kind of only synthetic and polypeptide expressed in proliferative cell, and at its content of akinete seldom, G1 begins to increase late period, and the S phase peaks, and the G2/M phase obviously descends, and therefore can be used as an index of proliferative activity.By measuring the fluorescence intensity of proliferating cell nuclear antigen, find that LBP can make cancerous cell PCNA content obviously reduce, confirmed that LBP plays obvious inhibitory action to the cancer cell multiplication process.

Gastrointestinal reaction is lighter in the untoward reaction of lobaplatin, does not see kidney and neurotoxicity, and less with other platinum medicine crossing drug resistants, anticancer therapeutic is good, and toxicity is low, can with multiple cancer therapy drug drug combination, improve curative effect.

Docetaxel has another name called docetaxel, is a kind of semisynthetic Ramulus et folium taxi cuspidatae class medicine, its mechanism of action is identical with paclitaxel, its anticancer mechanism mainly is to assemble microtubule and stop its depolymerization by the promotion tubulin, thereby makes the microtubule of cell lose normal function, causes the death of cancerous cell.The effect of Docetaxel stabilize microtubules is bigger 2 times than paclitaxel, and can induce the assembling of microtubule fasolculus, all can not obtain significant curative effect but do not change precursor quantity Docetaxel as the two wires and a line medication of the esophageal carcinoma, nasopharyngeal carcinoma adjuvant chemotherapy, be the chemotherapeutics that receives much concern in recent years.

The treatment mechanism difference of above-mentioned two kinds of medicines plays a part to replenish the Synergistic treatment cancer mutually on treatment for cancer.The present invention is through prolonged and repeated a large amount of experiments; surprised discovery; the pharmaceutical composition that lobaplatin and Docetaxel are formed is evident in efficacy in the treatment of the esophageal carcinoma and nasopharyngeal carcinoma; safety is good; the protection hemopoietic function of bone marrow; human body immunity improving power, and can effectively improve the effect of chemotherapeutic period patients ' life quality.

Illustrate how to implement the present invention below by embodiment, but the content that the present invention is not limited among the embodiment to be disclosed.

Experimental example

Embodiment about the treatment esophageal carcinoma is as follows:

Embodiment A-1: this experiment paired observation lobaplatin associating polyenoid (many west) paclitaxel and lobaplatin list product treat the clinical research of esophageal carcinoma effectiveness and safety.

Used medicine:

1. injection lobaplatin (LBP): 10mg, white lyophilized powder, lot number 20070101, every bottle contains lobaplatin in anhydride 10mg; Hainan Chang'an International Pharmaceutical Co., Ltd produces.

2. docetaxel injection: specification, 0.5ml:20mg contains the anhydrous docetaxel of 20mg in every 0.5ml solution, and greenish orange yellow is to orange-yellow clear liquid.Adjuvant is Tween 80,95% ethanol and water for injection, Wanle Pharmaceutical Co Ltd, Shenzhen.

Therapeutic scheme:

One, physical data

Local late period of 60 examples or transitivity patient with esophageal carcinoma are made a definite diagnosis through pathology, and patient's symptom is identical or similar, have can measure and/or valuable transitivity or part pathological changes in late period, are divided into two groups at random, and 30 examples are organized in treatment, matched group 30 examples.Treatment group patient, wherein male 12 examples, women 18 examples; Age 29-72 year, average 47 years old; Patient's height 1.66 ± 0.12M, body weight 60 ± 5Kg, body surface area 1.61 ± 0.19m ²The matched group patient, wherein male 15 examples, women 15 examples; Age 29-72 year, average 47 years old; Patient's height 1.67 ± 0.12M, body weight 60 ± 5Kg, body surface area 1.62 ± 0.19m ², two groups are not being had significant difference aspect age, the sex.Do routine blood test, hepatic and renal function, electrocardiogram etc. before the treatment and check equal Non Apparent Abnormality, no chemotherapy contraindication.

Two, Therapeutic Method

Treatment group: adopt LBP associating DTX, DTX 75mg/m ², add 0.9%N.S (normal saline) 250ml, intravenous drip 3 hours, average daily dose is 120.8mg, administration in the 1st day; LBP 30mg/m ², add among 5%G.S (glucose injection) 250ml, intravenous drip 2 hours, average daily dose is 48.3mg, administration in the 2nd day.21 days is one-period.Use the preceding conventional oral dexamethasone pretreatment of Docetaxel, 30min uses cimetidine, the reaction of diphenhydramine Polyglucan before the chemotherapy, and the 30min routine gives granisetron and prevents and treats vomiting before the chemotherapy; Give leukocyte increasing and thrombocytosis conventional medicine (interleukin-11) treatment if any the decline of leukocyte platelet after the chemotherapy.

Matched group: only adopt the lobaplatin treatment, usage and dosage is the same.If because experimenter's toxicity recovers can suitably postpone the time started of subsequent cycle less than foot one-period treatment standard, but retardation time the longest can not be above 14 days.Two cycle post-evaluation curative effects.

Annotate: the one-tenth body surface area general formula that Chinese are suitable for is: body surface area S=0.0061 * height (cm)+0.0128 * body weight (Kg)-0.1529, formula for reduction is: body surface area S=[height (m)-0.587] * 1.5 (adopting formula for reduction among the application), during treatment at individual differences, can suitably adjust using dosage at patient's concrete condition, reach optimum therapeuticing effect.As height 170cm, body weight 60kg adult male, its body surface area S is about 1.66m ²

Three, efficacy assessment standard

Press WHO solid tumor short term effect standard, divide and alleviate (CR), part alleviation (PR), stable (SD), progress (PD) fully.

CR: the lump complete obiteration, keep more than 1 month;

PR: lump dwindles＞and 50%, keep＜1 month;

NC: lump dwindles＜and 50% or increase＜25%;

PD: lump increases＞25% or new focus occurs.

Effective percentage is CR+PR, two cycle post-evaluations of chemotherapy curative effect; Disease control rate (CR+PR+SD) refers to that focus is dwindled or continual and steady period of greater than two months.

Four, toxicity evaluation:

When the patient accepts 1 cycle therapy, carry out safety analysis.Toxic reaction carries out observed and recorded and judgement according to the WHO anticarcinogen is acute with subacute toxicity performance and grade scale, is divided into the 0-4 level.

Five, statistical analysis

Adopt SPSS 10.0 statistical analysis softwares, rate relatively with the x check, measurement data adopts the t check.

Experimental result:

One, the observation of curative effect result sees Table A-1.

Table A-1 liang group curative effect is (%) relatively

Group	The example number	CR	PR	SD	PD	CR+PR	CR+PR+SD
								The treatment group	30	4(13.3)	12(40.0)	6(20.0)	8(26.7)	16(53.3)	22(73.3)
Matched group	30	2(6.7)	10(33.3)	5(16.7)	12(40.0)	12(40.0)	17(56.7)

Last table explanation: two groups all have good result to the treatment esophageal carcinoma, and two groups of curative effect comparing differences have significance (P＜0.01), and treatment group effect is better than matched group.

Two, the toxicity result sees Table A-2.

Table A-2 liang group toxicity relatively

The result shows, two groups of main adverse reactions are bone marrow depression, digestive tract reaction and alopecia, wherein treatment group bone marrow depression incidence rate is starkly lower than matched group, two groups of comparing differences have statistical significance (P＜0.05), show, compare the bone marrow depression that LBP associating DTX can alleviate patient's chemotherapeutic period with the LBP medicine with single.Obvious abnormal liver function, oral cavity, joint aches and neurotoxicity reaction all do not appear in two groups of patients in therapeutic process in addition, and the patient can tolerate mostly.

Embodiment A-2: this experiment paired observation lobaplatin associating Docetaxel treat esophageal carcinoma effectiveness and safety clinical research with cisplatin combined Docetaxel.

Used medicine:

1, injection lobaplatin (LBP): 10mg, white lyophilized powder, lot number 20070101, every bottle contains lobaplatin in anhydride 10mg; Hainan Chang'an International Pharmaceutical Co., Ltd produces.

2, docetaxel injection: specification, 0.5ml:20mg contains the anhydrous docetaxel of 20mg in every 0.5ml solution, and greenish orange yellow is to orange-yellow clear liquid.Adjuvant is Tween 80,95% ethanol and water for injection, Wanle Pharmaceutical Co Ltd, Shenzhen.

3, cisplatin for inj (DDP): 10mg; Yellow powder, lot number 36-014050304, adjuvant: mannitol, sodium chloride.Every bottle contains cisplatin in anhydride 10mg, and Jiangsu Haosen Pharmaceutical Co., Ltd produces.

Therapeutic scheme:

One, physical data

Local late period of 60 examples or transitivity patient with esophageal carcinoma are made a definite diagnosis through pathology, and patient's symptom is identical or similar, have can measure and/or valuable transitivity or part pathological changes in late period, are divided into two groups at random, and 30 examples are organized in treatment, matched group 30 examples.Treatment group patient, wherein male 15 examples, women 15 examples; Age 29-72 year, average 47 years old; Patient's height 1.66 ± 0.12M, body weight 60 ± 5Kg, body surface area 1.61 ± 0.19m ²The matched group patient, wherein male 14 examples, women 16 examples; Age 29-72 year, average 47 years old; Patient's height 1.67 ± 0.12M, body weight 60 ± 5Kg, body surface area 1.62 ± 0.19m ², two groups are not being had significant difference aspect age, the sex.Do routine blood test, hepatic and renal function, electrocardiogram etc. before the treatment and check equal Non Apparent Abnormality, no chemotherapy contraindication.

Two, Therapeutic Method

Treatment group: adopt LBP associating DTX, DTX 75mg/m ², add 0.9%N.S250ml, intravenous drip 3 hours, average daily dose is 120.8mg, administration in the 1st day; LBP 30mg/m ², add among the 5%G.S250ml, intravenous drip 2 hours, average daily dose is 48.3mg, administration in the 2nd day.21 days is one-period.Use the preceding conventional oral dexamethasone pretreatment of Docetaxel, 30min uses cimetidine, the reaction of diphenhydramine Polyglucan before the chemotherapy, and the 30min routine gives granisetron and prevents and treats vomiting before the chemotherapy; Should give leukocyte increasing and thrombocytosis conventional medicine (interleukin-11) treatment if any the decline of leukocyte platelet after the chemotherapy.

Matched group: adopt DDP associating DTX, DTX 75mg/m ², add 0.9%N.S 250ml, intravenous drip 3 hours, average daily dose is 121.5mg, administration in the 1st day; DDP 30mg/m ²The above normal saline of+250ml, average daily dose is 48.6mg, intravenous drip, the 1st day phase used weekly, routinely aquation.Treatment, usage is the same.If because experimenter's toxicity recovers can suitably postpone the time started of subsequent cycle less than foot one-period treatment standard, but retardation time the longest can not be above 14 days.Two cycle post-evaluation curative effects.

Annotate: the one-tenth body surface area general formula that Chinese are suitable for is: body surface area S=0.0061 * height (cm)+0.0128 * body weight (Kg)-0.1529, formula for reduction is: body surface area S=[height (m)-0.587] * 1.5, during treatment at individual differences, can suitably adjust using dosage at patient's concrete condition, reach optimum therapeuticing effect.As height 170cm, body weight 60kg adult male, its body surface area S is about 1.66m ²

Three, efficacy assessment standard

Press WHO solid tumor short term effect standard, divide and alleviate (CR), part alleviation (PR), stable (SD), progress (PD) fully.

CR: the lump complete obiteration, keep more than 1 month;

PR: lump dwindles＞and 50%, keep＜1 month;

NC: lump dwindles＜and 50% or increase＜25%;

PD: lump increases＞25% or new focus occurs.

Effective percentage is CR+PR, two cycle post-evaluations of chemotherapy curative effect; Disease control rate (CR+PR+SD) refers to that focus is dwindled or continual and steady period of greater than two months.

Four, safety evaluatio:

When the patient accepts 1 cycle therapy, carry out safety analysis.Toxic reaction carries out observed and recorded and judgement according to the WHO anticarcinogen is acute with subacute toxicity performance and grade scale, is divided into the 0-4 level.

Five, statistical analysis adopts SPSS 10.0 statistical analysis softwares, rate relatively with the x check, measurement data adopts the t check.

The result:

One, the observation of curative effect result sees Table A-3.

Table A-3 liang group curative effect is (%) relatively

Group	The example number	CR	PR	SD	PD	CR+PR	CR+PR+SD
								The treatment group	30	4(13.3)	12(40.0)	6(20.0)	8(26.7)	16(53.3)	22(73.3)
Matched group	30	3(10.0)	10(33.3)	5(16.7)	12(40.0)	13(43.3)	18(60.0)

Last table explanation: two groups of curative effect comparing differences have significant difference (P＜0.01), and treatment group effect obviously is better than matched group.

Two, untoward reaction result sees Table A-4.

Table A-4 liang group untoward reaction relatively

The result shows, two groups of main adverse reactions are bone marrow depression, digest and react and alopecia, wherein treatment group bone marrow depression incidence rate is starkly lower than matched group, two groups of comparing differences have statistical significance (P＜0.05), show, compare the bone marrow depression that LBP associating DTX can significantly alleviate patient's chemotherapeutic period with the DDP combination medicine.Obvious abnormal liver function, oral cavity, joint aches and neurotoxicity reaction all do not appear in two groups of patients in therapeutic process in addition, and the patient can tolerate mostly.

Experimental example A-3: lobaplatin and docetaxel consumption change the influence for the patient treatment effect

Select 40 examples to make a definite diagnosis patient with esophageal carcinoma through pathology, average weight is (60.0 ± 0.5) KG, and average height is (1.66 ± 0.14) rice, and the average body surface area of this sample is (1.61 ± 0.08) m ², by dosage escalation (dosage climbing) test, determine the optimal dose (used LBP is identical with embodiment A-1 with DTX) of the LBP associating DTX treatment esophageal carcinoma, estimating with treatment effective percentage, disease control rate, safety serves as to investigate index.Dose-limiting toxicity (DLT) is defined as: ANC (neutrophilic granulocyte), PLT (platelet) that the CTCAE4 level the 1st cycle appears in the experimenter reduce or anemia, or the non-haematics toxicity of CTCAE3,4 grades (except feel sick, vomiting and alopecia).DTX and LBP daily dose begin to increase progressively from low dosage respectively, are divided into 4 grades, and DTX is respectively: 65mg/m ²(average total daily dose 104.7mg), 75mg/m ²(average total daily dose 120.8mg), 80mg/m ²(average total daily dose 128.8mg), 90mg/m ²(average total daily dose 144.9mg), LBP is respectively: 20mg/m ²(average total daily dose 32.2mg), 30mg/m ²(average total daily dose 48.3mg), 40mg/m ²(average total daily dose 64.4mg), 50mg/m ²(average total daily dose 80.5mg), other conditions are identical with embodiment A-1, press the influence to therapeutic effect of the method investigation lobaplatin of experimental example A-1 and docetaxel consumption.The results are shown in Table A-5:

Table A-5 consumption changes The selection result

Experimental result shows, the lobaplatin and the DTX therapeutic effect of 4 groups of test dosages are all better, and effective percentage, disease control rate are higher.Experiment 3 and test 4 lower DLT incidence rate is arranged so the lobaplatin dosage range is chosen as (32.2～80.5) mg, is preferably (32.2～48.3) mg; The docetaxel dosage range is chosen as (104.7～144.9) mg, is preferably (104.7～120.8) mg.

Embodiment A-4: (annotate: each dosage form preparation of following lobaplatin and Docetaxel all adopts the conventional instrument in this area and conventional adjuvant, carrier etc. to make with the test of lobaplatin and Docetaxel generate a reagent box, except water, all the other reagent and raw material are the commercially available prod).

The LBP of various dosage forms and the preparation of DTX

For describing in each used in following preparation experiment reagent Table A-6 below.

Each reagent source explanation in each preparation experiment of Table A-6

Reagent

Sell producer

Lobaplatin	Hainan Chang'an International Pharmaceutical Co., Ltd, lot number 20061003
		Needle-use activated carbon	Shanghai Tang Xin activated carbon company limited
Starch	Weifang Sheng Tai pharmaceutcal corporation, Ltd
		Microcrystalline Cellulose	Ahua Pharmaceutical Co., Ltd., Liaocheng, Shandong
Mannitol	Shanghai nine nation's chemical industry company limiteies
		Hydroxypropyl emthylcellulose	The mountains and rivers, Anhui pharmaceutic adjuvant limited company
Sodium lauryl sulphate	The safe chemical industry company limited in last Taiwan Strait Exchange Association
		Cross-linking sodium carboxymethyl cellulose	Shanghai Celluloid Factory
PEG400	Hangzhou Xin Lanen Science and Technology Ltd.
		Soybean oil	The Jiangxi Province natural medicinal oil of Zhangshu City book on Chinese herbal medicine factory
Tween 80	Qingdao Tian Liyuan bio tech ltd
		Ethyl cellulose	Heda Co., Ltd, Shandong
Docetaxel	Hengrui Medicine Co., Ltd., Jiangsu Prov.

Lobaplatin injection: get 10g lobaplatin raw material, add the water for injection of preparating liquid total amount 80%, make its dissolving, the needle-use activated carbon that adds preparating liquid total amount 0.06% fully stirs, with 0.45 μ m membrane filtration, 2000ml again adds to the full amount of water for injection, 115 ℃ of pressure sterilizings 30 minutes, after the cooling, the incipient fusion filter bulb filters, embedding, 115 ℃ of hot repressings were sterilized 30 minutes, were prepared into 1000 of low capacity ejection preparations, every specification: 2ml:10mg (10mg is meant the consumption of active component lobaplatin);

Lobaplatin tablet: get 30g lobaplatin raw material and 25g starch and 40g microcrystalline Cellulose, cross 100 mesh sieves, with lobaplatin, starch and microcrystalline Cellulose mix homogeneously, add 10% starch slurry (binding agent commonly used, 5 gram starch are dissolved in the 50ml water) be mixed and made into soft material, make granule with 18 mesh sieves (Taylor standard sieve); Granule was 60 ℃ of dryings 4 hours, and the oven dry back adds 4g silicon dioxide and the 2g magnesium stearate is mixed, 20 mesh sieve granulate; Be pressed into 1000, specification: the 0.1g/ sheet;

Lobaplatin dispersible tablet: get 30g lobaplatin raw material and 15g starch and 15g microcrystalline Cellulose, cross 100 mesh sieves, with lobaplatin, 25g mannitol, starch and microcrystalline Cellulose mix homogeneously, add binding agent 1% hydroxypropyl emthylcellulose aqueous solution 50ml (hydroxypropyl emthylcellulose weight is 0.5g) and 0.3g sodium lauryl sulphate and be mixed and made into soft material, make granule with 18 mesh sieves; Granule was 50 ℃ of dryings 5 hours, and the oven dry back adds 4g silicon dioxide, 8g cross-linking sodium carboxymethyl cellulose and 2.5g magnesium stearate and mixes 20 mesh sieve granulate; Tabletting gets 1000 of dispersible tablets, specification: the 0.1g/ sheet.

Lobaplatin soft capsule: get 30g lobaplatin raw material, add the soft capsule adjuvant, described adjuvant is the PEG400 of 1.0 times of principal agent amounts, 0.4 times soybean oil, tween 80 and 0.4 times of ethyl cellulose of 0.6 times, abundant mixing, then feed liquid is transferred in the hopper of pellet processing machine, drip system or be pressed into 1000 of soft gelatin capsules, specification: 0.1g/ grain;

Injection Docetaxel: get Docetaxel 20g, tween 80 500g, PEG400 500g, mannitol 700g, add water for injection to 4800ml (water for injection of recipe quantity 80% commonly used), stirring makes Docetaxel be dissolved to the solution clarification, the active carbon that adds supplementary material total amount 0.2%, stirring at room 30 minutes, with 1.0 μ m filter membrane coarse filtration, filtrate adds the injection water to 6000ml (recipe quantity commonly used), reuse 0.22 μ m filter membrane fine straining, gained filtrate is carried out clarity, pH and content check, qualified back packing, fill, half tamponade is put into freeze dryer and is carried out lyophilizing, get 1000 of lyophilized injectable powders, specification: 20mg/ props up (20mg is meant active principle);

Docetaxel soft capsule: get 60g Docetaxel raw material, add the soft capsule adjuvant, described adjuvant is the PEG400 of 0.8 times of principal agent amount, 0.5 times soybean oil, tween 80 and 0.5 times of ethyl cellulose of 0.6 times, abundant mixing, then feed liquid is transferred in the hopper of pellet processing machine, drip system or be pressed into 1000 of soft gelatin capsules, specification: 0.2g/ grain;

Docetaxel sheet: get 60g Docetaxel and 35g starch and 50g microcrystalline Cellulose, cross 100 mesh sieves, with Docetaxel, starch and microcrystalline Cellulose mix homogeneously, add 10% starch slurry (5 gram starch are dissolved in the 50ml water) and be mixed and made into soft material, make granule with 18 mesh sieves; Granule was 60 ℃ of dryings 4 hours, and the oven dry back adds 4g silicon dioxide and the 3g magnesium stearate is mixed, 20 mesh sieve granulate; Be pressed into 1000, specification: the 0.15g/ sheet;

Docetaxel dispersible tablet: get 60g Docetaxel and 40g starch and 35g microcrystalline Cellulose, cross 100 mesh sieves, with Docetaxel, 60g mannitol, starch and microcrystalline Cellulose mix homogeneously, add binding agent 1% hydroxypropyl emthylcellulose aqueous solution 85ml (the 0.85g hydroxypropyl emthylcellulose is dissolved in the 85ml water) and 0.4g sodium lauryl sulphate and be mixed and made into soft material, make granule with 18 mesh sieves; Granule was 60 ℃ of dryings 4 hours, and the oven dry back adds 5g silicon dioxide, 10g cross-linking sodium carboxymethyl cellulose and 2.5g magnesium stearate and mixes 20 mesh sieve granulate; Tabletting gets 1000 of dispersible tablets, specification: the 0.2g/ sheet.

The preparation of test kit

Preparation method: the material or the container that adopt test kit packing reagent commonly used, with lobaplatin and the Docetaxel pharmaceutical preparation for preparing in commercial or the foregoing description, carry out packing, wherein, pharmaceutical preparation amount in the packaging unit of each packing in each test kit is selected according to the result of previous embodiment 1-3.

Test kit A: preparing three conventional packing pharmaceutical packing boxes (dividing another name first, second, third test kit unit), is that 5 of 10mg/2ml lobaplatin injection are sub-packed in the first test kit unit with the specification for preparing in the top experiment; With the specification for preparing in the top experiment is that 6 of the docetaxel freeze-drying powder ejection preparations that 20mg/ props up are sub-packed in the second test kit unit; 2 of commercial syringes are sub-packed in the 3rd test kit unit; In addition, stipulate in this test kit description that the lobaplatin in the described lobaplatin unit delivers medicine to the patient second day of medication cycle, Docetaxel delivers medicine to the patient first day of medication cycle in the described Docetaxel unit, and the described medication cycle is 21 days.

Test kit B: prepare three conventional packing pharmaceutical packing boxes (dividing another name first, second, third test kit unit), 2 of lobaplatin soft capsules that prepare in the top experiment are sub-packed in the first test kit unit; 2 of Docetaxel soft capsules are sub-packed in the second test kit unit; In addition, stipulate in this test kit description that the lobaplatin in the described lobaplatin unit delivers medicine to the patient second day of medication cycle, Docetaxel delivers medicine to the patient first day of medication cycle in the described Docetaxel unit, and the described medication cycle is 21 days.

Test kit C: prepare three conventional packing pharmaceutical packing boxes (dividing another name first, second, third test kit unit), 2 of lobaplatin sheets that prepare in the top experiment are sub-packed in the first test kit unit; 2 of Docetaxel sheets are sub-packed in the second test kit unit; In addition, stipulate in this test kit description that the lobaplatin in the described lobaplatin unit delivers medicine to the patient second day of medication cycle, Docetaxel delivers medicine to the patient first day of medication cycle in the described Docetaxel unit, and the described medication cycle is 21 days.

Test kit D: prepare three conventional packing pharmaceutical packing boxes (dividing another name first, second, third test kit unit), 2 of lobaplatin dispersible tablets that prepare in the top experiment are sub-packed in the first test kit unit; 2 of Docetaxel dispersible tablets are sub-packed in the second test kit unit; In addition, stipulate in this test kit description that the lobaplatin in the described lobaplatin unit delivers medicine to the patient second day of medication cycle, Docetaxel delivers medicine to the patient first day of medication cycle in the described Docetaxel unit, and the described medication cycle is 21 days.

Each reagent dosage in the mentioned reagent box is determined according to a treatment cycle.

Embodiment A-5 test kit of the present invention is used for the treatment of the treatment effectiveness evaluation experiment of patient with esophageal carcinoma

Therapeutic Method:

The patient with esophageal carcinoma of 40 examples through making a definite diagnosis, every group 10 people, all patient's height 1.63 ± 0.15M, body weight 64.5 ± 3.56Kg, body surface area 1.56 ± 0.22m ²Get lobaplatin and the Docetaxel of test with various dosage forms, specifically grouping and usage and dosage are:

A group: lobaplatin injection+injection Docetaxel, injection Docetaxel 75mg/m ²(average daily dose 117.0mg)+250ml normal saline, intravenous drip 3 hours, D1 intravenous drip; Lobaplatin injection 30mg/m ²(average daily dose 46.8mg)+5% glucose 250ml, intravenous drip 2 hours, D2;

B group: tablet (lobaplatin+Docetaxel); 2 of Docetaxels are oral, the every about 60mg of active component, D1; 2 of lobaplatin are oral, the every about 30mg of active component, D2;

C group: dispersible tablet (lobaplatin+Docetaxel); 2 of Docetaxels are oral, the every about 60mg of active component, D1; 2 of lobaplatin are oral, the every about 30mg of active component, D2;

D group: soft capsule (lobaplatin+Docetaxel); 2 of Docetaxels are oral, every about 60mg of active component, D1; 2 of lobaplatin are oral, every about 30mg of active component, D2;

21 days is one-period, observes the effectiveness of its therapeutic alliance patient with esophageal carcinoma according to the method for embodiment A-1.Result's following Table A-7:

Table A-7 different dosage form lobaplatin and Docetaxel curative effect are relatively

Group	The example number	CR	PR	SD	PD	CR+PR	CR+PR+SD
								The A group	10	2	4	2	2	6	8
The B group	10	0	3	2	5	3	5
								The C group	10	1	3	1	5	4	5
The D group	10	2	3	2	3	5	7

Result of the test shows, adopts the lobaplatin and the Docetaxel of different dosage form to cooperate with extensive phase patient with esophageal carcinoma, and its treatment has certain effect.

In test kit, the generate a reagent box is convenient to preserve with the 2 kinds of medicine independent packagings using of the treatment esophageal carcinoma, stable performance, good reproducibility has been avoided the loaded down with trivial details of artificial reagent preparation, be convenient in therapeutic process to adjust two kinds of absorption of active ingredient according to the difference between individual patients.

Embodiment about the treatment esophageal carcinoma is as follows:

The clinical research experiment of Embodiment B-1 lobaplatin associating Docetaxel treatment nasopharyngeal carcinoma effectiveness and safety

Used medicine

1. injection lobaplatin (LBP): 10mg/ props up, white lyophilized powder, and lot number 20070101, every contains lobaplatin in anhydride 10mg; Hainan Chang'an International Pharmaceutical Co., Ltd produces.

2. docetaxel injection: specification, 0.5ml:20mg contains the anhydrous docetaxel of 20mg in every 0.5ml solution, and greenish orange yellow is to orange-yellow clear liquid, and adjuvant is Tween 80,95% ethanol and water for injection, Wanle Pharmaceutical Co Ltd, Shenzhen.

3. carboplatin for inj (CBP): 100mg/ props up, white powder, and lot number 20050601, every contains carboplatin in anhydride 100mg, and Qilu Pharmaceutical Co., Ltd. produces.

Data and method

Physical data

The treatment group: lobaplatin+Docetaxel scheme, go into to organize patient's 41 examples, wherein male 28 examples, women 13 examples; Age 29-72 year, average 47 years old;

Matched group: Docetaxel+carboplatin scheme, go into to organize patient's 39 examples, wherein male 28 examples, women 11 examples; Age 29-72 year, average 47 years old.

All patient's height 1.66 ± 0.12M, body weight 60 ± 5Kg, body surface area 1.61 ± 0.19m ², and meet to be lowered to set condition: the recurrence that pathology confirms and (or) transitivity nasopharyngeal carcinoma patient, have at least one can measure focus; Functional status: Kamofsky scoring (quality of life scoring) 〉=70 minutes; WBE (leukocyte)＞4.0 * 10 ⁹/ L, PLT (platelet)＞100 * 10 ⁹/ L; Hepatic and renal function, electrocardiogram are normal; Diagnosis recurrence and (or) do not accept chemotherapy after the transitivity nasopharyngeal carcinoma; Recidivist after the radiotherapy, radiotherapy concluding time＞6 month; Estimate life span＞3 month.Go into to organize patient's pathology and be low differentiated squamous-cell carcinomas, wherein, person's 35 examples that have the metastasis (getting rid of vertigo moves), lung shifts 18 examples, hepatic metastases 9 examples, lung and bone shift 6 examples, the multiple transferase 12 example of liver, lung and bone, local recurrence person's 4 examples.

Annotate: the one-tenth body surface area general formula that Chinese are suitable for is: body surface area S=0.0061 * height (cm)+0.0128 * body weight (Kg)-0.1529, formula for reduction is: body surface area S=[height (m)-0.587] * 1.5 (adopting formula for reduction among the application), during treatment at individual differences, can suitably adjust using dosage at patient's concrete condition, so that obtain optimum therapeuticing effect.As height 170cm, body weight 60kg adult male, its body surface area S is about 1.66m ²

Therapeutic Method

A (treatment group): LBP 35mg/m ², add among 5%G.S (glucose) 250ml intravenous drip 2 hours, administration in the 1st day, DTX 75mg/m ², add 0.9%N.S (normal saline) 250ml, intravenous drip 3 hours, administration in the 1st day, 21 days one-periods, in this scheme in the one-period amount of drug in the body surface area average, the about 56mg of the average consumption of lobaplatin, the about 121mg of the average consumption of Docetaxel

(LBP and DTX branch are opened instillation).

B (matched group): CBP 300mg/m ², add among the 5%G.S 250ml intravenous drip, administration in the 1st day; DTX 75mg/m ², add 0.9%N.S 250ml, intravenous drip 3 hours, administration in the 2nd day, 21 days one-periods.In this scheme in the one-period amount of drug in the body surface area average, the about 483mg of the average consumption of carboplatin, the about 121mg of the average consumption of Docetaxel.

Routine gives 5-hydroxytryptamine receptor blocker preventing or arresting vomiting before each chemotherapy, and routine gives dexamethasone, diphenhydramine and cimetidine antiallergic, and suitably fluid infusion need not give the aquation diuresis, and 3 weeks were 1 course of treatment.All accept the chemotherapy in 2 cycles.

When curative effect and toxicity assessment are accepted 2 cycle therapy the patient, carry out therapeutic evaluation, be divided into according to RECIST solid tumor therapeutic evaluation standard and alleviate (CR) fully, part is alleviated (PR), stable (SD) and progress (PD); Total effective rate (ORR) accounts for the percent that can estimate the curative effect case for the case load of CR+PR.When the patient accepts 1 cycle therapy, carry out oxicity analysis, toxicity assessment standard (the common terminology criteria for adverse events that toxicity assessment is formulated by U.S. NCI, CTC AE) (the 3rd edition) estimated, and observe to feel sick respectively, vomiting, alopecia and bone marrow depression etc.

The statistical method survival analysis adopts the Kaplan.Meier method, carries out on the SPSS of statistical software 13.0.

The result

Curative effect is reacted the chemotherapy that this group patient has all accepted 2 courses of treatment, and two groups of effective percentage compare P＜0.01.See table B-1 for details.

Two groups of curative effects of table B-1 relatively

Group	The example number	CR	PR	SD	PD	ORR(CR+PR)％
							The A group	41	4	24	11	2	68.3
The B group	39	2	20	13	4	56.4

The survival analysis meta is followed up a case by regular visits to 18 months time, and it is 7.7 months that meta does not have the progression of disease phase, and survival rate was 90.5% in 1 year, and median survival interval is 18.6 months.

The main toxic reaction of toxic reaction is bone marrow depression, paraesthesia, muscle and joint aches, feel sick, vomiting and alopecia, but all can tolerate.Based on I, II degree, relevant with Docetaxel toxicity; Muscle, joint aches generally continue 2-5d, give the nonsteroidal medicine and suit the medicine to the illness and can recover behind the pain management, do not see the infringement and the cardiac toxicity of obvious hepatic and renal function.See table B-2 for details.

The toxic reaction of table B-2 lobaplatin associating Docetaxel treatment recurrence or transitivity nasopharyngeal carcinoma

Annotate: two groups of every toxic reactions compare P＜0.05.

Embodiment B-2 lobaplatin treatment nasopharyngeal carcinoma and the effectiveness of plus cisplatin in treatment nasopharyngeal carcinoma and the clinical research contrast experiment of safety

Data and method

Medicine:

1. injection lobaplatin (LBP): 10mg/ props up, white lyophilized powder, and lot number 20070101, every contains lobaplatin in anhydride 10mg; Hainan Chang'an International Pharmaceutical Co., Ltd produces.

2. cisplatin for inj (DDP): 10mg/ props up, yellow powder, lot number 36-014050304, adjuvant: mannitol, sodium chloride; Every contains the cisplatin amount in anhydride 10mg, and Jiangsu Haosen Pharmaceutical Co., Ltd produces.

Therapeutic scheme:

1. nasopharyngeal carcinoma patient 38 examples, male 28 examples, women 10 examples, 36～69 years old age, The median age 42 years old, body surface area 1.63 ± 0.15m ², all be diagnosed as the non-keratinization type cancer of nasopharynx through histopathology.Patient's cassette scoring 〉=80 minutes, clinical stages is local late period, is treatment first.The patient is divided into treatment group, each 19 example of matched group at random, and two groups of clinical datas have comparability.

(2.A treatment group): LBP 35mg/m ², total about 57mg of consumption, the 1st day quiet, 21 days is one-period;

B (matched group): DDP 100mg/m ², total about 163mg of consumption, among the adding normal saline 250ml, the 1st day quiet, 21 days is one-period; All check hemogram, hepatic and renal function, blood glucose and electrocardiogram before two groups of chemotherapy, check hemogram during the treatment weekly, the bone marrow depression of IV level occurs and promptly stop chemotherapy.Treat 2 cycles post-evaluation curative effect and toxicity, evaluation methodology is all identical with Embodiment B-1.

The result

Observation of curative effect sees Table B-3.

Two groups of curative effects of table B-3 relatively

Group	The example number	CR	PR	SD	PD	ORR(CR+PR)％
							The treatment group	19	3	11	4	1	73.7
Matched group	19	2	8	5	4	52.6

Last table explanation: two groups of curative effect comparing differences have significant difference (P＜0.05), and treatment group effect is better than matched group.

Toxic reaction sees Table B-4:

Table B-4 toxicity is decomposed (CTC standard)

Two groups of untoward reaction are mainly I, the reaction of II level skin mucosa, bone marrow depression, gastrointestinal symptom, and last table explanation: bone marrow depression of treatment group and gastrointestinal symptom are starkly lower than matched group (P＜0.05).

Experimental example B-3: lobaplatin and docetaxel consumption change the influence for the patient treatment effect

Select 40 examples to make a definite diagnosis the nasopharyngeal carcinoma patient through pathology, body weight is (61.0 ± 3.8) KG, and height is (1.65 ± 0.18) rice, and the body surface area of this sample is (1.59 ± 0.27) m ², by dosage escalation (dosage climbing) test, determine the optimal dose (used LBP is identical with Embodiment B-1 with DTX) of LBP associating DTX treatment, estimating with treatment effective percentage, disease control rate, safety serves as to investigate index.Dose-limiting toxicity (DLT) is defined as: ANC (neutrophilic granulocyte), PLT (platelet) that 4 grades of CTCAE the 1st cycle appears in the experimenter reduce or anemia, or the non-haematics toxicity of CTCAE3,4 grades (except feel sick, vomiting and alopecia).The use amount of DTX and LBP begins to increase progressively from low dosage respectively in course of treatment, is divided into 4 grades, and DTX is respectively: 65mg/m ²(average total daily dose 104mg), 75mg/m ²(average total daily dose 120mg), 80mg/m ²(average total daily dose 128mg), 90mg/m ²(average total daily dose 144mg), LBP is respectively: 20mg/m ²(average total daily dose 32mg), 30mg/m ²(average total daily dose 48mg), 40mg/m ²(average total daily dose 64mg), 50mg/m ²(average total daily dose 80mg) press the influence to therapeutic effect of the method investigation lobaplatin of experimental example B-1 and docetaxel consumption.The results are shown in Table B-5:

Table B-5 consumption changes The selection result

Experimental result shows, the lobaplatin and the DTX therapeutic effect of 4 groups of test dosages are all better, and effective percentage, disease control rate are higher.Wherein test 3 and test 4 lower DLT incidence rate is arranged,, be preferably (32-48) mg so the lobaplatin dosage range is chosen as (32-80) mg; The docetaxel dosage range is chosen as (104-144) mg, is preferably (104-120) mg.

Embodiment B-4: (annotate: each dosage form preparation of following lobaplatin and Docetaxel all adopts the conventional instrument in this area and conventional adjuvant, carrier etc. to make with the test of lobaplatin and Docetaxel generate a reagent box, except water, all the other reagent and raw material are the commercially available prod).

The LBP of various dosage forms and the preparation of DTX

For describing among each used in following preparation experiment reagent table B-6 below.

Each reagent source explanation in each preparation experiment of table B-6

Lobaplatin injection: get 10g lobaplatin raw material, add the water for injection of preparating liquid total amount 80%, make its dissolving, the needle-use activated carbon that adds preparating liquid total amount 0.06% fully stirs, with 0.45 μ m membrane filtration, 2000ml again adds to the full amount of water for injection, 115 ℃ of pressure sterilizings 30 minutes, after the cooling, the incipient fusion filter bulb filters, embedding, 115 ℃ of hot repressings were sterilized 30 minutes, were prepared into 1000 of low capacity ejection preparations, every specification: 2ml:10mg (10mg refers to the consumption of active component lobaplatin);

Lobaplatin tablet: get 30g lobaplatin raw material and 25g starch and 40g microcrystalline Cellulose, cross 100 mesh sieves, with lobaplatin, starch and microcrystalline Cellulose mix homogeneously, add 10% starch slurry (binding agent commonly used, 5 gram starch are dissolved in the 50ml water) be mixed and made into soft material, make granule with 18 mesh sieves (Taylor standard sieve); Granule was 60 ℃ of dryings 4 hours, and the oven dry back adds 4g silicon dioxide and the 2g magnesium stearate is mixed, 20 mesh sieve granulate; Be pressed into 1000, specification: the 0.1g/ sheet;

Lobaplatin dispersible tablet: get 30g lobaplatin raw material and 15g starch and 15g microcrystalline Cellulose, cross 100 mesh sieves, with lobaplatin, 25g mannitol, starch and microcrystalline Cellulose mix homogeneously, add binding agent 1% hydroxypropyl emthylcellulose aqueous solution 50ml (hydroxypropyl emthylcellulose weight is 0.5g) and 0.3g sodium lauryl sulphate and be mixed and made into soft material, make granule with 18 mesh sieves; Granule was 50 ℃ of dryings 5 hours, and the oven dry back adds 4g silicon dioxide, 8g cross-linking sodium carboxymethyl cellulose and 2.5g magnesium stearate and mixes 20 mesh sieve granulate; Tabletting gets 1000 of dispersible tablets, specification: the 0.1g/ sheet;

Lobaplatin soft capsule: get 30g lobaplatin raw material, add the soft capsule adjuvant, described adjuvant is tween 80 and 0.4 times of amount ethyl cellulose of the soybean oil of the PEG400 of 1.0 times of principal agent amounts, 0.4 times of amount, 0.6 times of amount, abundant mixing, then feed liquid is transferred in the hopper of pellet processing machine, drip system or be pressed into 1000 of soft gelatin capsules, specification: 0.1g/ grain;

Injection Docetaxel: get Docetaxel 20g, tween 80 500g, PEG400 500g, mannitol 700g, add water for injection to 4800ml (water for injection of recipe quantity 80% commonly used), stirring makes Docetaxel be dissolved to the solution clarification, the active carbon that adds supplementary material total amount 0.2%, stirring at room 30 minutes, with 1.0 μ m filter membrane coarse filtration, filtrate adds the injection water to 6000ml (recipe quantity commonly used), reuse 0.22 μ m filter membrane fine straining, gained filtrate is carried out clarity, pH and content check, qualified back packing, fill, half tamponade is put into freeze dryer and is carried out lyophilizing, obtain 1000 of injection Docetaxel lyophilized preparation, specification: 20mg/ props up (amount that 20mg is meant active component);

Docetaxel soft capsule: get 60g Docetaxel raw material, add the soft capsule adjuvant, described adjuvant is tween 80 and 0.4 times of amount ethyl cellulose of the soybean oil of the PEG400 of 1.0 times of principal agent amounts, 0.6 times of amount, 0.5 times of amount, abundant mixing, then feed liquid is transferred in the hopper of pellet processing machine, drip system or be pressed into 1000 of soft gelatin capsules, specification: 0.2g/ grain;

Docetaxel sheet: get 60g Docetaxel and 35g starch and 50g microcrystalline Cellulose, cross 100 mesh sieves, with Docetaxel, starch and microcrystalline Cellulose mix homogeneously, add 10% starch slurry (10g starch is dissolved in the 100ml water) and be mixed and made into soft material, make granule with 18 mesh sieves; Granule was 60 ℃ of dryings 4 hours, and the oven dry back adds 3g silicon dioxide and the 2g magnesium stearate is mixed, 20 mesh sieve granulate; Be pressed into 1000, specification: the 0.15g/ sheet;

Docetaxel dispersible tablet: get 60g Docetaxel and 40g starch and 35g microcrystalline Cellulose, cross 100 mesh sieves, with Docetaxel, 60g mannitol, starch and microcrystalline Cellulose mix homogeneously, add binding agent 1% hydroxypropyl emthylcellulose aqueous solution 85ml (the 0.85g hydroxypropyl emthylcellulose is dissolved in the 85ml water) and 0.4g sodium lauryl sulphate and be mixed and made into soft material, make granule with 18 mesh sieves; Granule was 60 ℃ of dryings 4 hours, and the oven dry back adds 4g silicon dioxide, 8g cross-linking sodium carboxymethyl cellulose and 2.5g magnesium stearate and mixes 20 mesh sieve granulate; Tabletting gets 1000 of dispersible tablets, specification: the 0.2g/ sheet.

The preparation of test kit

Preparation method: the material or the container that adopt test kit packing reagent commonly used, with lobaplatin and the Docetaxel pharmaceutical preparation for preparing in commercial or the foregoing description, carry out packing, wherein, pharmaceutical preparation amount in the packaging unit of each packing in each test kit is selected according to the result of previous embodiment 1-3.

Test kit A: preparing three conventional packing pharmaceutical packing boxes (dividing another name first, second, third test kit unit), is that 6 of 10mg/2ml lobaplatin injection are sub-packed in the first test kit unit with the specification for preparing in the top experiment; With the specification for preparing in the top experiment is that 7 of the polyenoid west paclitaxel freeze drying powder ejection preparations that 20mg/ props up are sub-packed in the second test kit unit; 2 of commercial syringes are sub-packed in the 3rd test kit unit; In addition, stipulate in this test kit description that the lobaplatin in the described lobaplatin unit delivers medicine to the patient first day of medication cycle, Docetaxel delivers medicine to the patient first day of medication cycle in the described Docetaxel unit, and the described medication cycle is 21 days.

Test kit B: prepare three conventional packing pharmaceutical packing boxes (dividing another name first, second, third test kit unit), 2 of lobaplatin soft capsules that prepare in the top experiment are sub-packed in the first test kit unit; 2 of Docetaxel soft capsules are sub-packed in the second test kit unit; In addition, stipulate in this test kit description that the lobaplatin in the described lobaplatin unit delivers medicine to the patient first day of medication cycle, Docetaxel delivers medicine to the patient first day of medication cycle in the described Docetaxel unit, and the described medication cycle is 21 days.

Test kit C: prepare three conventional packing pharmaceutical packing boxes (dividing another name first, second, third test kit unit), 2 of lobaplatin sheets that prepare in the top experiment are sub-packed in the first test kit unit; 2 of Docetaxel sheets are sub-packed in the second test kit unit; In addition, stipulate in this test kit description that the lobaplatin in the described lobaplatin unit delivers medicine to the patient first day of medication cycle, Docetaxel delivers medicine to the patient first day of medication cycle in the described Docetaxel unit, and the described medication cycle is 21 days.

Test kit D: prepare three conventional packing pharmaceutical packing boxes (dividing another name first, second, third test kit unit), 2 of lobaplatin dispersible tablets that prepare in the top experiment are sub-packed in the first test kit unit; 2 of Docetaxel dispersible tablets are sub-packed in the second test kit unit; In addition, stipulate in this test kit description that the lobaplatin in the described lobaplatin unit delivers medicine to the patient first day of medication cycle, Docetaxel delivers medicine to the patient first day of medication cycle in the described Docetaxel unit, and the described medication cycle is 21 days.

Each reagent dosage in the mentioned reagent box is determined according to a treatment cycle.

Embodiment B-5 test kit of the present invention is used for the treatment of nasopharyngeal carcinoma patient's treatment effectiveness evaluation experiment

Therapeutic Method:

The extensive phase nasopharyngeal carcinoma patient of 60 examples through making a definite diagnosis, every group 15 people, all patient's height 1.66 ± 0.14M, body weight 64 ± 3Kg, body surface area 1.61 ± 0.21m ²Get lobaplatin and the Docetaxel of test with various dosage forms, specifically grouping and usage and dosage are:

A group: lobaplatin injection+injection Docetaxel, lobaplatin injection 35mg/m ²(the about 56mg of consumption)+5% glucose 250ml, intravenous drip 2 hours, D1; Injection Docetaxel 75mg/m ²(the about 121mg of consumption)+250ml normal saline, intravenous drip 3 hours, D1;

B group: tablet (lobaplatin+Docetaxel); 2 (the every about 30mg of active component) are oral for the lobaplatin sheet, D1; 2 (the every about 60mg of active component) are oral for Docetaxel, D1;

C group: dispersible tablet (lobaplatin+Docetaxel); 2 (the every about 30mg of active component) are oral for the lobaplatin sheet, D1; 2 (the every about 60mg of active component) are oral for Docetaxel, D1;

D group: soft capsule (lobaplatin+Docetaxel); 2 (every about 30mg of active component) are oral for lobaplatin, D1; 2 (every about 60mg of active component) are oral for Docetaxel, D1;

21 days is one-period, treats 2 all after dates, observes nasopharyngeal carcinoma effectiveness of extensive phase of its therapeutic alliance according to the method for Embodiment B-1.The result is shown in following table B-7:

Table B-7 lobaplatin and Docetaxel different dosage form curative effect are relatively

Result of the test shows, adopts the lobaplatin and the Docetaxel of different dosage form to cooperate with extensive phase nasopharyngeal carcinoma patient, and its treatment has certain effect.

In test kit, the generate a reagent box is convenient to preserve with the 2 kinds of medicine independent packagings using of treatment nasopharyngeal carcinoma, stable performance, good reproducibility has been avoided the loaded down with trivial details of artificial reagent preparation, be convenient in therapeutic process to adjust two kinds of absorption of active ingredient according to the difference between individual patients.

Claims (26)

1. treat esophageal carcinoma pharmaceutical composition for one kind, it contains the lobaplatin of the treatment effective dose that supplies simultaneously, separates or use in order as combination formulations and the Docetaxel of treatment effective dose.

2. compositions according to claim 1 in weight portion, contains 20-50 part lobaplatin and 65-90 part Docetaxel, preferably contains 20-30 part lobaplatin and 65-75 part Docetaxel, more preferably contains 30 parts of lobaplatin and 75 parts of Docetaxels.

3. a treatment esophageal carcinoma test kit comprises first test kit unit that contains lobaplatin and the second test kit unit that contains Docetaxel.

4. test kit according to claim 3, the described first test kit unit that contains lobaplatin comprises 20-50mg/m ², preferred 20-30mg/m ², more preferably 30mg/m ²Daily dose/unitary lobaplatin unit, the described second test kit unit that contains Docetaxel comprises 65-90mg/m ², preferred 65-75mg/m ², more preferably 75mg/m ²Daily dose/unitary Docetaxel unit, described daily dose is the quality of active component.

5. according to claim 3 or 4 described test kits, the described first test kit unit that contains lobaplatin comprises 32.2-80.5mg, preferred 32.2-48.3mg, more preferably 48.3mg daily dose/unitary lobaplatin unit, the described second test kit unit that contains Docetaxel comprises 104.7-144.9mg, preferred 104.7-120.8mg, more preferably 120.8mg daily dose/unitary Docetaxel unit, and described daily dose is the quality of active component.

6. test kit according to claim 5, the described first test kit unit that contains lobaplatin comprises 1-3 32.2-80.5mg, preferred 32.2-48.3mg, more preferably 48.3mg daily dose/unitary lobaplatin unit, and the described second test kit unit that contains Docetaxel comprises 1-3 104.7-144.9mg, preferably 104.7-120.8mg, more preferably 120.8mg daily dose/unitary Docetaxel unit.

7. a package of packing the treatment esophageal carcinoma with medicine comprises packaging space second packaging unit that contains first packaging unit of lobaplatin and contain Docetaxel independent of each other.

8. package according to claim 7, the described first test kit unit that contains lobaplatin comprises 20-50mg/m ², preferred 20-30mg/m ², more preferably 30mg/m ²Daily dose/unitary lobaplatin unit, the described second test kit unit that contains Docetaxel comprises 65-90mg/m ², preferred 65-75mg/m ², more preferably 75mg/m ²Daily dose/unitary Docetaxel unit, described daily dose is the quality of active component.

9. according to claim 7 or 8 described packages, described first packaging unit that contains lobaplatin comprises 32.2-80.5mg, preferred 32.2-48.3mg, more preferably 48.3mg daily dose/unitary lobaplatin unit, described second packaging unit that contains Docetaxel comprises 104.7-144.9mg, preferred 104.7-120.8mg, more preferably 120.8mg daily dose/unitary Docetaxel unit, and described daily dose is the quality of active component.

10. package according to claim 9, the described first parcel post unit that contains lobaplatin comprises 1-3 32.2-80.5mg, preferred 32.2-48.3mg, more preferably 48.3mg daily dose/unitary lobaplatin unit, and described second packaging unit that contains Docetaxel comprises 1-3 104.7-144.9mg, preferably 104.7-120.8mg, more preferably 120.8mg daily dose/unitary Docetaxel unit.

11. according to each described package among each described test kit or the claim 7-10 among the claim 3-6, also comprise description, stipulate in this description, lobaplatin in the described lobaplatin unit delivers medicine to the patient second day of medication cycle, Docetaxel delivers medicine to the patient first day of medication cycle in the described Docetaxel unit, and the described medication cycle is 21 days.

12. test kit according to claim 11 or package, described lobaplatin and described Docetaxel are ejection preparation; Soft capsule; Or tablet.

13. a treatment nasopharyngeal carcinoma pharmaceutical composition, it contains the lobaplatin of the treatment effective dose that supplies simultaneously, separates or use in order as combination formulations and the Docetaxel of treatment effective dose.

14. compositions according to claim 13 in weight portion, contains 20-50 part lobaplatin and 65-90 part Docetaxel, preferably contains 20-30 part lobaplatin and 65-75 part Docetaxel, more preferably contains 30 parts of lobaplatin and 75 parts of Docetaxels.

15. a treatment nasopharyngeal carcinoma test kit comprises first test kit unit that contains lobaplatin and the second test kit unit that contains Docetaxel.

16. test kit according to claim 15, the described first test kit unit that contains lobaplatin comprises 20-50mg/m ², preferred 20-30mg/m ², more preferably 30mg/m ²Daily dose/unitary lobaplatin unit, the described second test kit unit that contains Docetaxel comprises 65-90mg/m ², preferred 65-75mg/m ², more preferably 75mg/m ²Daily dose/unitary Docetaxel unit, described daily dose is the quality of active component.

17. according to claim 15 or 16 described test kits, the described first test kit unit that contains lobaplatin comprises 32-80mg, preferred 32-48mg, more preferably 48mg daily dose/unitary lobaplatin unit, the described second test kit unit that contains Docetaxel comprises 104-144mg, preferred 104-120mg, more preferably 120mg daily dose/unitary Docetaxel unit, and described daily dose is the quality of active component.

18. test kit according to claim 17, the described first test kit unit that contains lobaplatin comprises 1-3 32-80mg, preferred 32-48mg, more preferably 48mg daily dose/unitary lobaplatin unit, and the described second test kit unit that contains Docetaxel comprises 1-3 104-144mg, preferably 104-120mg, more preferably 120mg daily dose/unitary Docetaxel unit.

19. a package of packing the treatment nasopharyngeal carcinoma with medicine comprises packaging space second packaging unit that contains first packaging unit of lobaplatin and contain Docetaxel independent of each other.

20. package according to claim 19, the described first test kit unit that contains lobaplatin comprises 20-50mg/m ², preferred 20-30mg/m ², more preferably 30mg/m ²Daily dose/unitary lobaplatin unit, the described second test kit unit that contains Docetaxel comprises 65-90mg/m ², preferred 65-75mg/m ², more preferably 75mg/m ²Daily dose/unitary Docetaxel unit, described daily dose is the quality of active component.

21. according to claim 19 or 20 described packages, described first packaging unit that contains lobaplatin comprises 32-80mg, preferred 32-48mg, more preferably 48mg daily dose/unitary lobaplatin unit, described second packaging unit that contains Docetaxel comprises 104-144mg, preferred 104-120mg, more preferably 120mg daily dose/unitary Docetaxel unit, and described daily dose is the quality of active component.

22. package according to claim 21, the described first parcel post unit that contains lobaplatin comprises 1-3 32-80mg, preferred 32-48mg, more preferably 48mg daily dose/unitary lobaplatin unit, and described second packaging unit that contains Docetaxel comprises 1-3 104-144mg, preferably 104-120mg, more preferably 120mg daily dose/unitary Docetaxel unit.

23. according to each described package among each described test kit or the claim 19-22 among the claim 15-18, also comprise description, stipulate in this description, Docetaxel all delivered medicine to the patient at first day of the medication cycle in lobaplatin in the described lobaplatin unit and the described Docetaxel unit, and the described medication cycle is 21 days.

24. test kit according to claim 23 or package, described lobaplatin and described Docetaxel are ejection preparation; Soft capsule; Or tablet.

25. being combined in of lobaplatin and Docetaxel prepares the application for the treatment of in the esophageal carcinoma or the medicine for nasopharyngeal.

26. application according to claim 25, described lobaplatin and Docetaxel consumption are (20-50)/(65-90) by weight, preferred (20-30)/(65-75).