RU2393897C1 - Method of treatment patients with locally advanced forms of cervical cancer - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to oncology and may be used in treatment of cervical cancer. The method includes chemotherapy with 5-fluorouracil for 5 days every day, followed by simultaneous administering of platinum drugs and radiotherapy according to the scheme of dynamic dose fractionation with extended fractions of 4 Gy to the pelvis during the first 3 days. Then radiation therapy is continued in small fractions of 2.5 Gy once a day up to a total focal dose of 50 Gy, with additionally administered derinat-gel once a day to vaginal tube and simultaneously in the form of microclysters into rectum in scope of 10-15 ml during the first 5 days of treatment. Then for 3-4 hours prior of or 1-2 hours after each session of radiation and after radiation therapy course termination the installations into vaginal tube in the same extent are continued for 2-3 weeks.

EFFECT: method enables to increase resorption of tumor due to increasing the total focal dose up to 50,0 Gy with a decrease in the number and expressivity of radiation reactions due to restoration of oxidative-antioxidant processes and reduce the concentration of free radicals in tissues under influence of derinat gel.

2 ex

Description

The invention relates to medicine, in particular to oncology, and can be used to treat patients with locally advanced forms of cervical cancer.

A known method of treating locally advanced cancer of the uterus (patent of the Russian Federation for the invention No. 2243771, IPC A61K 31/513, A61N 5/10, publ. 2005), including the use of chemotherapy and intrauterine radiation. As a chemotherapeutic agent, paratumoral cyclophosphamide and fluorouracil on a creamy basis are administered. The disadvantage of this method is the limited impact on the zones of regional lymph nodes due to the lack of remote exposure.

A known method of treating local relapses of cervical cancer (RF patent for the invention No. 2240114, IPC A61N 5/10, publ. 2004), comprising introducing a tampon into the vagina with a therapeutic composition containing viferon, linseed oil, doxorubicin, methotrexate and hydroxyurea into within 10 days 10 hours before the daily exposure session. The disadvantage of this method is that its sufficiently effective use is possible only in the treatment of local relapses, and in the primary treatment of cervical cancer, a systemic effect of chemotherapy drugs is necessary not only on the tumor, but also on possible existing metastases. Therefore, the proposed introduction of drugs, including, including viferon, in a known manner, does not provide the necessary effect on the affected area.

Closest to the claimed is a method of treating a locally advanced form of cervical cancer (A.V. Boyko et al. “Using radiomodification to expand indications for radical radiation treatment of patients with locally advanced forms of cervical cancer”, Kazan Medical Journal. Volume LXXXI No. 4, 2000, p. 287-289), including chemotherapy with 5-fluorouracil for 5 days daily, followed by the simultaneous administration of a platinum-containing drug and gamma therapy according to a dynamic dose fractionation scheme with a larger fractions of 4 Gy per pelvis for the first 3 days, and then continued radiation therapy with small fractions in multifraction mode at 1, 25 Gy 2 times a day with an interval of 4-5 hours. The disadvantage of this method is the inability to carry out a continuous course of treatment, since the double toxic effect of chemotherapy and ionizing radiation leads to an increase in the response from normal tissues, which often does not allow to complete the course of treatment, reduces the quality of life of patients, reduces the effectiveness of treatment .

The claimed invention is directed to solving the problem of increasing the effectiveness of treatment.

Using in clinical practice the proposed method allows to achieve several technical (therapeutic) results:

- the possibility of increasing SOD to 50.0 Gy, which is equivalent to 62.0 Gy with classical fractionation of the dose of ionizing radiation,

- reduction in the number and severity of local radiation reactions,

- increased resorption of a cervical tumor,

- reduction of the effect of ionizing radiation on normal tissues.

These therapeutic results in the implementation of the invention are achieved due to the fact that, as in the known method of treating patients with locally advanced forms of cervical cancer, chemotherapy with 5-fluorouracil is carried out for 5 days daily, followed by the simultaneous administration of a platinum-containing drug and radiation therapy according to the dynamic dose fractionation with enlarged fractions of 4 Gy per pelvis for the first 3 days, and then continued radiation therapy with small fractions.

A feature of the proposed method is that irradiation with small fractions is carried out at 2.5 Gy once a day to a total focal dose of 50 Gy, with the addition of Derinat gel once a day in the vaginal tube and at the same time as a microclyster in the rectum in a volume of 10-15 ml for the first 5 days of treatment, then 3-4 hours before or 1-2 hours after each irradiation session and after the end of the course of radiation therapy for 2-3 weeks, the installation continues into the vaginal tube in the same volume .

The invention consists in the following.

The impact on tumor tissue according to the proposed scheme provides the opportunity to increase the fine fractions up to 2.5 Gy and irradiate 1 time per day without daily dose splitting up to the total focal dose of SOD up to 50.0 Gy, which is equivalent to 62.0 with the classical fractionation of the dose of ionizing radiation . Protecting the surrounding normal tissues with derinat gel allows you to enhance the damaging effect on the tumor, which is necessary for a locally advanced process, and allows you to bring the specified dose without pronounced radiation reactions.

Derinat gel (a hydrogel preparation based on sodium alginate with sodium deoxyribonucleinate) belongs to universal metabolic modulators and is a unique polymer molecule with a multifaceted positive effect on human hemostasis in the absence of toxicity and contraindications. It has a non-specific general biological stimulating effect on all organs and tissues, normalizes the immune status, stabilizes hematopoiesis, and enhances tissue regeneration. Its introduction during the entire course of treatment and after the end of the course of radiation therapy ensures the restoration of oxidative-antioxidant processes and a decrease in the concentration of free radicals in normal tissues included in the volume of radiation. In hydrogel material, sodium alginate, a natural biopolymer obtained from brown algae rich in trace elements, is used as a depot for derinate. The water-soluble base of the polymer causes the absence of a film that inhibits cellular respiration.

The proposed treatment regimen for locally advanced forms of cervical cancer can reduce the number and severity of local radiation reactions, enhance the resorption of a cervical tumor and reduce the effect of ionizing radiation on normal tissues.

The implementation of the method shown in specific clinical examples.

Example 1

Patient L-va E.A., born in 1947, and / b SA-4214, was in the radiological department of the Moscow P.A. Herzen from July 31 to September 14, 2007. DIAGNOSIS: cervical cancer of the III b st., T3bN1M0, mixed growth form, bilateral parametric, uterine and metastatic variant. Condition after chemoradiation treatment. Morphologically - cons. No. 1597/07 - infiltrative growth of moderately differentiated squamous cell carcinoma. Cytology: puncture of the iliac l / node on the right. No. 6448-49 / 07 - metastasis of squamous cell carcinoma. Concomitant diseases: hr. hemorrhoids. Chr. cystitis. The tumor marker SCC before treatment is 17.1 ng / ml (normal up to 1.5 ng / ml). Ultrasound of the small pelvis and abdominal cavity from 07.20.2007: when examining the liver, kidneys, inguinal and supraclavicular areas, mammary glands - without features. The uterus is not enlarged (41 × 42 × 57 mm), the cervix is represented by a hypoechoic formation with uneven contours, the dimensions of the altered neck are 36 × 46 × 48 mm. Changes pass to the body of the uterus - in its n / 3 along the front and back walls, along the front wall they reach up to 3/3 of the body inclusively. The uterine cavity is expanded to 6 mm, the structures of the described formation protrude into its lower part. On the left in the parametry, hyperechoic infiltrate is up to 33 mm thick, up to 34 mm wide, to the right - up to 29 mm thick, up to 29 mm wide. The ovaries are not visualized. Posterior to the right external iliac vessels, slightly below the bifurcation of the common iliac vessels, the hypoechoic node 28 × 20 × 17 mm (punctured). Single nodes up to 11 × 10 × 8 mm anterior to the left external iliac vessels. At the level of the lower mesogastric, the inter-aortocaval node of the hypoechoic structure is 14 × 11 × 9 mm. Conclusion: an echographic picture of a disease of the cervix, utero-parametric variant. Secondary lesion of the lymph node of the right iliac region, altered l / nodes in the left iliac region. In the interaortocaval region, the l / nodes are secondarily altered.

Upon admission to the radiology department: in the mirrors the cervix is hypertrophied up to 5 cm in D. The external pharynx and anterior lip are occupied by an exophytic tumor. Palpation of the cervix is increased in size to 5-6 cm in D in both portions, woody density. The body of the uterus is not enlarged. Appendages are not determined. On the left in the parametria in the anterior sections is a narrow specific infiltrate to the pelvic wall. To the right is free. Cystoscopy from 08/03/2007 - hr. cervical cystitis, without exacerbation. Sigmoidoscopy from 08/02/2007 - the intestinal mucosa was examined up to 25 cm - without pathology.

From July 31 to September 14, 2007 a course of chemoradiotherapy was carried out. Treatment began with the introduction of 400 mg 5-fluorouracil intravenously for 5 days (OD = 2.0 g), after 2 days, 30 mg cisplatin intravenously with hyperhydration and latran - 3 days (OD = 90 mg), and irradiation was started at the same time with the regimen dynamic fractionation, by the method of biaxial pendulum swing with ROD in t.A - 4 Gy (3 days), then 2.5 Gy, to OD = 17.5 Gy, field 6 × 20 cm. From the first day of introduction of 5- fluorouracil patient had applications in the vagina and microclysters in the rectum of the gel with Derinat in the amount of 10 ml. With the start of irradiation, Derinat gel was administered 3 hours before or 2 hours after the irradiation session.

After which intracavitary irradiation was attached, and the remote continued to the zones of parametric and lymphogenous metastasis, ROD, i.e. B - 2.5 Gy. The administration of Derinat gel was continued in the same mode. Received total focal doses: A - 86 Gy, i.e. B - 63 Gy, bladder - 50 Gy, rectum - 37 Gy.

The treatment was satisfactory, reactions from the rectum and bladder were not noted.

Gynecological status at discharge: in the mirrors, the cervix is formed, not enlarged, the mucosa with slight epithelitis of the 2nd degree. Palpation of the cervix and body of the uterus is not enlarged, mobile. The cervix is of moderate density. Appendages are not determined. In the parameters, moderate severity.

Discharged in satisfactory condition under the supervision of an oncologist. Thus, the use of the proposed methodology allowed the patient with locally advanced cervical cancer and concomitant pathology to chemoradiate treatment in full without interruptions and to achieve clinical cure.

Example 2

Patient D-va N.I., born in 1944, and / b SA-7074, was in the radiological department of Moscow P.A. Herzen from 12/13/2007 to 02/07/2008 DIAGNOSIS: cancer of the cervical stump IIA art., T2aNxM0, mixed growth form, vaginal version. Morphologically - cons. No. 2631/07 - a moderately differentiated invasive cervical adenocarcinoma.

Concomitant diseases: peptic ulcer of the duodenum, in remission. Chr. cholecystopancreatitis.

Ultrasound of the pelvis and abdominal cavity from 04/04/2007: when examining the liver, kidneys, paraaortic region, retroperitoneal space - without focal pathology. The stump of the cervix is 35.4 × 34.5 mm, the external contour is uneven, clear, the structure is clearly heterogeneous due to hypoechoic inclusions in the central departments. Over 2 cm, the vagina is thickened to 24 mm with a similar structure. To the right of the stump of the anechogenic structure is an area of 20 × 12.3 × 13.5 mm. In the projection of parametria, infiltrates are not visualized. There is no free fluid in the pelvic cavity. Conclusion: an echographic picture of cervical stump disease, vaginal involvement, diffuse changes in the liver, diffuse changes in the pancreas.

Gynecological status: the vagina is narrow, deep. In the mirrors, the cervix is small, completely tumor-like. The tumor passes to the vaginal arches, which are sealed. Palpation of the cervix stump in the supravaginal portion increased to 4 cm in diameter. The uterine body was promptly removed in 1989 for myoma, the appendages were removed in 1999 for ovarian cystoma. In the parameters - moderate severity on both sides.

Sigmoidoscopy from December 6, 2007 - the intestinal mucosa was examined up to 25 cm. hemorrhoids (not pronounced), in remission.

From 14.12 to 06.02. In 2008, a course of chemoradiotherapy was conducted.

For the purpose of radiomodification, the patient received an introductory course of 5FU at 400 mg for 5 days (OD-2 Gy) and cisplatin at 30 mg N3 (OD-90 mg). Against the background of the introduction of cisplatin, radiation therapy with remote gamma therapy in the dynamic fractionation mode was started, ROD including A - 4 Gy × 3 days, then ROD - 2.5 Gy, up to OD = 27 Gy. Further, irradiation was continued by alternating intracavitary gamma-therapy and remote, which was carried out on the zones of parametric and lymphogenous metastasis, RTI, i.e. B - 2.5 Gy. Received total focal doses: A - 92 Gy, dome of the cervical stump - 85 Gy, i.e. B - 55 Gy, bladder - 57 Gy, rectum - 54 Gy.

From the beginning of treatment and throughout its duration, applications were made to the vaginal mucosa and microclysters in the rectum with Derinat gel in a volume of 10 ml 2 hours after irradiation. The entire course of treatment was completed in the planned volume, without interruption.

Gynecological status at discharge: the vagina is free, the mucous membrane of the cervix is covered with moderate islet (2 degree) epithelitis. Palpation of the cervix stump is small, pasty. Appendages are not determined. On the left in the parametria is moderate severity. On the right - free. Discharged in satisfactory condition with clinical cure under the supervision of an oncologist. During the dynamic observation of signs of the resumption of tumor growth was not observed. The phenomena of epithelitis after irradiation were stopped after 2 months.

The proposed method allows to increase the number of organ-saving operations and thereby improve the quality of life of patients, reduce disability.

Claims (1)

A method for treating patients with locally advanced forms of cervical cancer, including chemotherapy with 5-fluorouracil for 5 days daily, followed by the simultaneous administration of a platinum-containing drug and radiation therapy according to the dynamic dose fractionation scheme with enlarged fractions of 4 Gy per pelvis for the first 3 days, and then the continuation of radiation therapy in small fractions, characterized in that the irradiation with small fractions is carried out at 2.5 Gy 1 time per day to a total focal dose of 50 Gy, Derinat gel is administered once a day into the vaginal tube and simultaneously in the form of microclysters into the rectum in a volume of 10-15 ml for the first 5 days of treatment, then 3-4 hours before or 1-2 hours after each irradiation session and after the course of radiation therapy for 2–3 weeks, installations in the vaginal tube in the same volume continue.