RU2260434C1 - Method for treating locally metastasing forms bladder's cancer - Google Patents

Abstract

FIELD: medicine, oncology.

SUBSTANCE: the present innovation deals with treating locally metastasing forms of bladder's cancer at T2b-4N0-1M0 stages. It deals with performing chemotherapy due to fractional introduction of total therapeutic dosage of cytostatic preparation into pubic bone - adriamycin at a single dosage being not more than 30 mg every other day per one course up to total dosage of 70 mg/m². After each injection one should introduce per 2 ml 2%-lidocaine solution through the same needle. For patients with contra-indications for systemic chemotherapy total adriamycin dosage should be decreased twice to be distributed for three injections. The method increases adriamycin concentration in tumor at optimal way and mode of its injection by providing decreased number of toxic complications, in patients above 75 or with severe accompanied pathology, among them.

EFFECT: higher efficiency of therapy.

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Description

The invention relates to medicine, oncology and can be used to treat locally advanced forms of bladder cancer T2b-4 N0-1 M0.

There are currently known methods of treating locally advanced forms of bladder cancer by systemic chemotherapy consisting of intravenous [1] administration of cytostatics, for example, cisplatin at a dose of 75 mg / m ² once a month or adriamycin 30 mg / m ² daily for 3 days [2]. However, the disadvantages of these methods of treatment are: a) high systemic toxicity of the cytostatic; b) insufficient concentration of chemotherapy in the tumor; c) limited scope due to the presence of contraindications for systemic chemotherapy in a certain category of patients. In particular, for patients older than 75 years of age or suffering from severe concomitant pathology, systemic chemotherapy is contraindicated and such patients are only on symptomatic treatment.

Closest to the proposed method in technical essence is a method comprising chemotherapy, which consists in the intraosseous administration of cisplatin in a dose of 30 mg once every three days to the pubic bone until a total dose of 75-90 mg / m ^{2 is} reached [3], and subsequent surgical treatment. The disadvantage of this method of treatment is the limited scope due to the impossibility of using this method in patients with contraindications to chemotherapy with platinum drugs, and the lack of effectiveness of platinum drugs in a number of patients with bladder cancer.

A new technical task is to increase the effectiveness of chemotherapy by enhancing the effect and reducing the number of complications, as well as expanding the scope of the method.

The problem is solved by a new method of treating locally advanced forms of bladder cancer, including chemotherapy by fractionally administering a total therapeutic dose of cytostatic to the pubic bone, with 30 mg adriamycin every other day administered in a single course to a total total dose of 70 mg / m ² , and after each injection 2 ml of a 2% lidocaine solution is injected through the same needle; for patients with contraindications for systemic chemotherapy, the total dose of adriamycin is halved and distributed into three injections.

The method is as follows. In a patient with verified invasive bladder cancer T _2b-4 N _0-1 M ₀ , the pubic bone is punctured (from the side of the maximum tumor lesion), retreating 2.5 cm from the midline. Preliminarily, 2-3 ml of a 2% lidocaine solution is injected intracostally, then 30 mg of adriamycin dissolved in 15 ml of physiological saline is injected intraosseously. After the administration of the cytostatic agent, an additional 2 ml of a 2% lidocaine solution is introduced through the same needle. The introduction of adriamycin is performed every other day, the total total dose is 70 mg / m ² . Conduct only one chemotherapy course in a combination treatment program for locally advanced bladder cancer before surgery.

EXAMPLE 1. Patient C., 53 g. Diagnosis: Bladder cancer T _3b N ₁ M ₀ . Histologically transitional cell carcinoma. According to cystoscopy, a tumor up to 6 cm in diameter occupies the right side wall, the back, goes to the neck of the bladder, the right mouth is not visualized, villous with patches of necrosis, contact bleeds, on a wide base. According to computed tomography, the tumor in the region of the right and back walls extends to the peribubble fiber, infiltrates the right orifice of the ureter, causing a partial block of the right kidney. From 1 to 2 cm in diameter, metastatically altered iliac lymph nodes. General condition on the Karnowski scale of 80%. Creatinine clearance 65 at the time of admission. After installing a permanent stand in the right ureter and increasing creatinine clearance to 72, the patient received a course of intraosseous chemotherapy with adriamycin according to the proposed scheme. The total total dose of adriamycin per course was 120 mg. Of the side effects, mild leukopenia was observed. The therapeutic effect after intraosseous chemotherapy is regarded as partial. During control cystoscopy, the tumor was determined up to 2.5 cm in diameter on the right side wall with a transition to the back. According to computed tomography, a therapeutic effect was also noted. In terms of further combined treatment, a bladder resection with ureterocystoanastomosis and pelvic lymphadenectomy was performed, followed by three courses of systemic immunotherapy with Intron A for prophylactic purposes. The relapse-free period was 13 months.

EXAMPLE 2. Patient G., 62 g. Diagnosis: Bladder cancer T _2b N ₀ M ₀ . Histologically transitional cell carcinoma. According to cystoscopic examination, the main tumor was located above the left orifice up to 2.5 cm in diameter, villous, on a broad base, 4 smaller tumors with a diameter of 0.1 to 0.5 cm superficial on the posterior and lateral walls. The mouths of the ureters are intact. Computed tomography showed that the main tumor spread to the serous membrane, not sprouting into the near-bubble tissue. The left ureter in the intramural section is partially involved in the pathological process. CLS and the ureter on the left are expanded to 1 degree. No data were received for metastatic lesions of the lymph nodes. From concomitant pathology there were: CHD: CH 2 FC. H-2. PEAKS (1989) against the background of GB W art. In terms of combined treatment with the first stage, the patient received a course of intraosseous monochemotherapy with adriamycin according to the proposed scheme, taking into account the presence of concomitant pathology, the total total dose was 60 mg per course. Of the side effects, mild leukopenia was noted and additional correction of the pathology of the cardiovascular system was required. The effect was evaluated one month after the end of chemotherapy and was regarded as partial. During control cystoscopy, the diameter of the main tumor was 1.5 cm, the other 4 tumors were not visualized. Subsequently, the patient underwent transurethral resection of the bladder and a course of prophylactic intravesical immunotherapy with BCG vaccine. The follow-up period after combined treatment was 6 months, for which there were no signs of relapse. The effect of the combined treatment is regarded as complete.

The technique of intraosseous administration is explained by the features of bone tissue, which determines the maximum volume of the injected solution is not more than 20 ml. Therefore, the maximum single administration of adriamycin is 30 mg (dilution of 10 mg of adriamycin per 5 ml of solvent). In order to prevent subcutaneous tissue necrosis when adriamycin gets under the skin, when the needle is removed, it is pre-washed with a solution of lidocaine in an amount of 2 ml.

With intraosseous injection into the pubic bone, the drug is distributed through the lymphatic pathways and a series of venous plexuses: the shameful (Santorievo) plexus, the bladder plexus, and the upper lateral parts of the utero-cystic plexus. Due to this route of administration of the cytostatic agent, its concentration in the tumor increases 4 times, as well as in the regional lymph nodes affected by metastases, the exposure time of the chemotherapy drug to the tumor tissue is prolonged, as a result of the drug’s long presence in the lymphatic and bloodstream.

It is proved that this route of administration, which was not used for adriomycin in the treatment of bladder cancer, can significantly reduce its toxicity and maximize the dose of this cytostatic in the tumor tissue. As a result of prolonged circulation of the cytostatic agent in the venous plexuses and slow release into the systemic circulation, the concentration of the chemotherapy drug in the systemic circulation is reduced compared to the intravenous route of administration, which explains the low toxicity of adriamycin during its intraosseous administration.

The applied technique for intraosseous administration of the total therapeutic dose of adriamycin in divided doses allows prolonging the effect of the cytostatic on the tumor while maintaining the therapeutic concentration of the cytostatic in the tumor tissue. For elderly patients older than 70 years without a pronounced concomitant pathology of the cardiovascular system and liver, the dose of adriamycin does not decrease. Practical experience has shown that systemic toxicity in elderly patients with this treatment method is moderate, which is explained by the fractional administration of low doses of a chemotherapy drug, as well as a low concentration of cytostatic in the systemic circulation. For patients with the presence of concomitant pathology of the cardiovascular system and liver, in connection with the possible systemic toxic effect of the cytostatic on vital organs and systems, it is recommended to reduce the total dose by half.

During the study, the optimal total dose of adriamycin for intraosseous administration of 70 mg / m ² , which corresponds to the average intravenous, was established. A decrease in the total therapeutic dose with intraosseous administration compared with the intravenous route of administration does not lead to a decrease in the effect due to the preservation of the therapeutic concentration of the drug in the tumor, and also helps to reduce its systemic toxicity. Studies have shown the safety of intraosseous administration of adriamycin.

Thus, the proposed method allows to increase the effectiveness of treatment by increasing the concentration of adriamycin in the tumor as a result of choosing the optimal route and mode of administration, as well as reducing the number of complications associated with the toxic effects of cytostatic when administered intravenously on vital organs and systems of the body for a high concentration of the latter in the systemic circulation. In addition, the proposed method allows its use in patients older than 70 years and in patients with contraindications for systemic chemotherapy.

The technique of intraosseous administration of cytostatic drugs is very simple, accessible to any doctor, does not require special costs and equipment.

LITERATURE

1. Wallace D.M., Raghavan D., Kelly K.A., et al. neo-adjuvant cisplatin therapy in invasive transitional cell carcinoma of the bladder.//Br J Urol 67: 608-615, 1991.

2. Mashkovsky M.D.// Medicines. T.2. - 1988. - S.460-461.

3. Selivanov S.P., Chen M.N., Usynin E.A., Isaeva S.N., Khursevich N.A. Treatment of bladder cancer with intraosseous administration of platidiam.// Actual problems of clinical oncology, mat. Int. Conf., Ulan-Ude, 1999, p. 195-196.

Claims (1)

A method of treating locally advanced bladder cancer, including conducting chemotherapy by fractionally administering a total therapeutic dose of cytostatic to the pubic bone, characterized in that adriamycin is administered in a single dose of not more than 30 mg every other day in one course to a total dose of 70 mg / m ² , and after for each injection, 2 ml of a 2% solution of lidocaine is injected through the same needle, for patients with contraindications for systemic chemotherapy, the total dose of adriamycin is halved and divided into three injections.