RU2368381C1 - Method of neoadjuvant chemotherapy of invasive bladder cancer - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine and namely to oncourology and can be used for treatment of bladder tumours. The method is implemented in the following way: during the period prior to the operation there created is depot of cytostatic incubated with autoplasma in regional lymphatic nodes. For that purpose 50 ml of blood is taken from the patient, centrifugated at the speed of 1500 rpm during 40 min; 15 ml of the obtained autoplasma is added to cytostatic diluted in the proportion of 0.9% NaCl per 5 ml, and incubated during 1 hour at t=37°C. Then puncture of lymphatic vessel on the back of the foot is performed and cytostatic with autoplasma is injected; repeated injection in one and the same limb is carried out in 12 days.

EFFECT: use of invention provides the effect on tumour and its regional metastases owing to keeping the remedy in lymphatic bed for a long time and its being deposited in regional lymphatic nodes at low probability of complications.

1 ex

Description

The invention relates to medicine, in particular to oncology, and can be used in the treatment of patients with a malignant tumor of the bladder at the II-III stages of the tumor process.

A known method of chemotherapeutic treatment of invasive bladder cancer (see the book "Clinical Oncourology" / Under the editorship of Matveev BP - M .: 2003, p. 366-368; Guidelines for the chemotherapy of tumor diseases / Under the editorship of Translatorova N .I. - M., 2005) consisting in the application of the M-VAC scheme (Methotrexate - 30 mg / m ² iv on the 1st day, Vinblastine - 3 mg / m ² iv on the 2nd day , Doxorubicin (Adriamycin) - 30 mg / m ² on the 2nd day, Cisplatin - 70 mg / m ² iv in the second day. Doses of methotrexate and vinblastine are repeated on the 15th and 22nd day at normal blood counts. Repeated to urs after 4 weeks).

Systemic polychemotherapy has a number of pronounced side effects due to its toxicity: complications from the cardiovascular system, gastrointestinal tract, hematopoietic organs, coagulation system, and immunity, which leads to the need to interrupt specific treatment.

The well-known "Method for the treatment of bladder cancer by autohemochemotherapy" (see Nazarova OE Autohemochemotherapy of locally advanced bladder cancer: Abstract of thesis. Candidate of Medical Sciences, RN / D. 2003). The method includes administering to the patient antitumor chemotherapeutic drugs in medium therapeutic doses:

cyclophosphamide, doxorubicin, cisplatin, diluted in 150 ml of autologous blood taken from a patient from a vein in 2 sterile vials with 50 ml of glyugitsir. Chemotherapy drugs are injected into vials in physiological saline. The composition is incubated for 30 minutes. at t ° = 36.5-37.0 ° C in a thermstat followed by reinfusion of autologous blood with cytostatics to a patient i / v drip under conditions of hyperhydration. The method is effective, however, has drawbacks: it is accompanied by toxicity, does not affect the regional lymphatic system.

The well-known "Method of endolymphatic polychemotherapy" (see the book "Endolymphatic polychemotherapy in the clinic" / Ed. Sidorenko Yu.S., Rostov-on-Don, 1998, p. 120), we have chosen as a prototype. The method of endolymphatic polychemotherapy of bladder cancer was used for functional contraindications to surgery and radiation treatment in a neoadjuvant mode. The results of chemotherapy (for a course of 2000 mg of cyclophosphamide and 2000 mg of 5-fluorouracil or 100-150 mg of Tiotef) were evaluated by improving the general condition of the general condition, reducing dysuria and hematuria. However, the known method has disadvantages: the endolymphatic route of administration of chemotherapeutic drugs, providing an effect on the entire regional lymphatic collector, affects the change in peripheral blood counts.

After infusion, a decrease in the number of leukocytes compared with the initial level is observed. A slight decrease in toxicity does not allow a full course of polychemotherapy. Changes in peripheral blood parameters after ECPT are of interest for further clinical studies in this area.

The aim of the invention is the effect on the tumor of the bladder and regional lymph nodes, reducing the complications of chemotherapy.

This goal is achieved by the fact that in the preoperative period a depot of a chemotherapeutic drug incubated with autoplasma is created in regional lymph nodes: 50 ml of the patient’s blood is sampled, centrifuged at a speed of 1500 rpm for 40 min, the autoplasma obtained in a volume of 15 ml is combined with a cytostatic (cyclophosphamide 2000 mg), diluted in 5.0 ml of 0.9% NaCl and incubated at t = 37 ° C for 1 hour, then a lymphatic vessel is punctured on the back of the foot and a chemopreparation is incubated with autoplasma, the next injection of cyto Tatikios in the lymphatics of the same legs can be carried out after 10 days in receptacles opposite leg - after 6-7 days.

The invention "A method for the neoadjuvant chemotherapy of invasive bladder cancer" is new, as it is not known from the level of medicine in the treatment of patients with malignant bladder cancer in stages II-III of the tumor process.

The novelty of the invention lies in the fact that in the preoperative period a depot of an antitumor chemotherapy is created on the autoplasm of a patient with bladder cancer of the II-III stage of the tumor process, has never been used in medical practice for malignant tumors of the bladder.

Due to the lack of selectivity, existing antitumor drugs damage both tumor cells and normal, fast-growing cells, primarily bone marrow cells. With an increase in the total dose of cytostatic along with an increase in the antitumor effect, as a rule, inhibition of the function of the hematopoietic organs develops. Despite the fact that endolymphatic chemotherapy allows the administration of massive doses of chemotherapy drugs, this technique does not lead to a pronounced decrease in toxicity of the latter. Changes in the parameters of peripheral blood after ECPT are of undoubted interest, since it can be used to judge the degree of toxic effects on the body of massive doses of chemotherapy drugs administered endolymphatically.

Endolymphatic autoplasmochemotherapy is a promising neoadjuvant treatment for malignant tumors of the bladder in stages II-III of the process. The method of administration of cytostatic on autoplasma helps to increase the selectivity and effectiveness of antitumor treatment.

The method allows to significantly reduce the frequency, severity and duration of toxic reactions, to avoid a number of complications that limit the use of systemic chemotherapy.

The regression of the primary tumor site and metastatically changed lymph nodes, achieved in a short time, contributes to the further successful technical execution of the operation.

The invention "Method for the neoadjuvant chemotherapy of invasive bladder cancer" is industrially applicable, as it can be reproduced in health facilities, cancer research institutes, cancer dispensaries and other medical institutions involved in the treatment of patients with bladder cancer.

The "method of neoadjuvant chemotherapy for invasive bladder cancer" is performed as follows: by puncture of a peripheral vein, 50 ml of the patient’s blood is drawn into a sterile vial with 10 ml of Glyugitsir, followed by centrifugation of blood (speed 1500 rpm) for 40 minutes. Thus obtained patient's plasma is combined in a volume of 15 ml of autoplasm with a cytostatic agent (Cyclophosphamide 2000 mg, diluted in 5 ml of 0.9% NaCl) and incubated at t = 37 ° C for 1 hour. Then, according to the appropriate technique, a lymphatic vessel is punctured on the back of the foot, followed by the introduction of a chemotherapeutic drug incubated with the patient's plasma. Repeated administration of cytostatic is performed after 12 days. Immediately before the operation, the dynamics of the patient’s objective status is assessed (patient complaints and the severity of clinical manifestations, ultrasound of the bladder to assess the dynamics of the tumor process). In the postoperative period, the degree of drug tumor pathomorphism and changes in regional lymph nodes is assessed.

An example of a specific implementation of the "Method neoadjuvant chemotherapy for infiltrative bladder cancer."

Patient K., 71 years old, medical record No. C-2340 / h, was admitted to the Department of Oncourology 02/18/08 with complaints of difficulty, painful, rapid urination, periodically-macrohematuria (last time 8.01.08) According to the examination (ultrasound from 01.21.08 - hyperechoic formations 0.8 × 2.3 cm in size are located on the right side wall of the bladder, including TUR-biopsy of the bladder performed at the patient’s place of residence (State Clinical Oncology Dispensary State Health Department of the Krasnodar Territory Department of Health), g .but. No. 106115-116 - moderately differentiated transitional cell carcinoma with invasion to the muscle layer, the diagnosis is established: T2NoMo bladder cancer, class. column 2. According to cystoscopy (dated 11/10/07, discharge epicrisis No. 07.22123 dated 10/16/07) performed at the Regional Clinical Oncological Dispensary State Health Institution of the Krasnodar Territory Health Department — 1-3 segments along the back wall with a transition to the right side wall merged with each other villous tumors, ranging in size from 1.5 to 3.0 cm. In the neck of the bladder enlarged adenomatous nodes, on the surface of which are circular tumor growth. The right mouth in the tumor zone, the left mouth outside the tumor zone, peristalsis.

02/19/08 - a right-handed endolymphatic infusion of 2000 mg of Cyclophosphamide incubated with 15 ml of the patient’s plasma was performed. On day 5, a decrease in dysuria was noted. 03.03.08 (after 12 days) - repeated endolymphatic administration of cytostatic in the right lower limb was performed. According to laboratory tests (OAK, biochemical blood test), the level of leukocytes, urea, creatinine during chemotherapy is within normal limits. No adverse reactions from the gastrointestinal tract, cardiovascular systems, blood

On March 11, 2008, a control ultrasound scan was performed, according to which a hyperechoic formation without a clear contour, 0.8 cm in size, is located at the base of the bladder on the right. March 12, 2008, an operation was performed - TUR-vaporization of the bladder (В 2-3 S along the right side wall, 4 sections of the altered mucosa, each 1 × 1.5 cm in size, each suspicious of a tumor, were revealed 1 cm above the mouth of the right ureter, 1–1.5 cm in the left side, similar sections with a total size of 1 × 1.5 cm. In the postoperative period without complications The patient was discharged with adequate urination, dysuria no.

The technical and economic effectiveness of the "Method of neoadjuvant chemotherapy for invasive bladder cancer is that:

- A cytostatic agent, administered endolymphatically on the autoplasma, provides not only a long stay of the drug in the lymphatic channel (due to its deposition in regional lymph nodes, as well as binding to plasma proteins), but also affects both the tumor itself and its regional metastases.

- The likelihood of developing complications of endolymphatic chemotherapy compared with systemic PCT is reduced.

- improves the quality of life of the patient by maintaining an adequately functioning bladder

- the duration of the relapse-free period increases.

Claims (1)

A method of neoadjuvant chemotherapy for bladder cancer, characterized in that in the preoperative period a depot of a cytostatic agent incubated with autoplasma is created in regional lymph nodes: 50 ml of the patient’s blood is sampled, centrifuged at 1500 rpm for 40 min, 15 ml of the obtained autoplasma combined with a cytostatic agent diluted in 5 ml of 0.9% NaCl and incubated at t = 37 ° C for 1 h, a lymphatic vessel is punctured on the back of the foot and a cytostatic agent with autoplasma is introduced, repeated administration into the same limb is carried out they melt in 12 days.