RU2350338C2 - Method of treatment of superficial cancer of bladder - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention concerns medicine, namely to oncology and can be used for treatment sick of a superficial cancer of a bladder. The way is carried out as follows. Transurethral resection and the subsequent intravesical introduction of chemical preparations and vaccine of Calmette and Guerin, incubated with autoplasma are spent, and also intravenous introduction of chemical preparations, incubated with a cellular suspension.

EFFECT: method enlarges time of recurrence-free course of process at the expense of chemical preparations depot creation and the vaccine of Calmette and Guerin in a zone of the damaged organ and simultaneous chemical sanitation of blood vessels using cytostatics.

Description

The invention relates to medicine, namely to oncology, and can be used to treat patients with superficial and recurrent bladder cancer.

It is known that the main method of treating superficial bladder cancer is surgery in the amount of transurethral resection (TUR), which provides local tumor control in 80% of patients (in the book: "Modern Diagnosis and Surgery of Bladder Cancer" / Edited by Kogan M .I. And Perepechay V.A. - Publishing House of Russian State Medical University, Rostov-on-Don, 2002 - P.61-66).

However, this method does not ensure the absence of relapse of cancer in other parts of the bladder. Moreover, each subsequent relapse has a greater depth of invasion and a more aggressive course with an increased risk of subsequent lymphogenous and hematogenous dissemination of the process. Therefore, it is currently believed that TUR needs to be supplemented with postoperative chemotherapy.

The well-known "Method for the treatment of bladder cancer" (see patent No. 2181848 from 11/27/1999, Bull. No. 33).

The essence of the method lies in the fact that in patients with locally advanced and recurrent forms of bladder cancer in a neoadjuvant mode, 100 ml of blood is taken sequentially in two sterile vials with glucose. Then, doxorubicin at a dose of 40-60 mg / m ² and cyclophosphamide at a dose of 600-800 mg / m ^{2 are} introduced into the first bottle and cisplatin at a dose of 80-100 mg / m ² into the second bottle. Both vials are incubated in a thermostat at a temperature of 37 ° C for 30 minutes, followed by reinfusion of the first vial of autologous blood with doxorubicin and cyclophosphamide first. Then, to reduce nephrotoxicity, 1000 ml of a 5% glucose solution is hydrated and the blood with cisplatin is reinfused. In conclusion, a hemodesis solution with 2 ml of lasex is administered. The introduction of chemotherapy is carried out once a week for 2-3 weeks, i.e. 2-3 infusions are given for the course of treatment.

The use of the autohemochemotherapy method allows to reduce the size of the tumor, increase resectability, improve the immediate condition of the patient in the preoperative period by reducing toxicity, stopping hematuria, pain and pain during urination, does not have an immunosuppressive effect on the immune system.

However, this method was used in patients with locally advanced and recurrent reform of bladder cancer, who subsequently underwent surgery, and was not used for superficial forms of bladder cancer after transurethral resection. An undoubted drawback is the lack of a therapeutic effect directly on the pathological focus - a malignant tumor.

There is a method of treating superficial bladder cancer, aimed at reducing the risk of relapse, in which TUR is supplemented by intravesical administration of chemotherapy drugs or BCG vaccine (Guide to the chemotherapy of tumor diseases / Edited by N.I. Perevodchikova. - 2nd ed., Add. - M .: Practical medicine, 2005. - S.315-316), selected as a prototype.

The following drugs are used for intravesical chemotherapy:

- Mitomycin - 40 mg in 40 ml of isotonic sodium chloride solution;

- Epirubicin (Pharmorubicin) - 50 mg in 50 ml of distilled water;

- Doxorubicin - 50 mg in 50 ml of distilled water;

- Thiotepa (Thiophosphamide) - 60 mg in 50 ml or 30 mg in 30 ml of a 0.5% solution of novocaine;

- Cisplatin - 60 mg in 50-100 ml of isotonic sodium chloride solution.

For the prevention of relapse after TUR, the drugs are administered 1 time per month for 10-12 months.

BCG vaccine is administered once a week for two hours for 6 weeks at a dose of 50-100 mg diluted in 50 ml of isotonic sodium chloride solution. If the effect is insufficient, continue treatment for another 6 weeks.

However, the effectiveness of intravesical chemotherapy ranges from 40 to 70%. The activity of the BCG vaccine to prevent relapse is slightly higher, therefore, it is preferred for intravesical treatment. At the same time, the use of BCG vaccine has a number of contraindications, in particular, the transferred or existing tuberculosis process, the formation of tuberculoma granulomas in the bladder. The use of chemopreparations, introduced on traditional official solvents, also has its drawbacks: pronounced toxic effects (nausea, vomiting), unformed and cardiotoxicity caused by the administration of cisplatin and doxorubicin, respectively, significant inhibition of patients' immunity, which entails the addition of fungal and microbial diseases. An important disadvantage of this method of treatment is its duration. As a rule, a rare patient punctually observes the monthly schedule for the administration of chemotherapy drugs, which, of course, worsens the results of chemotherapy due to the formation of drug resistance.

The aim of the present invention is to improve the results of treatment of patients with bladder cancer T _a-1 N ₀ M ₀ .

The goal was achieved in that patients with superficial bladder cancer after completing TUR, cisplatin and BCG vaccine are successively introduced into the bladder, incubated every 30 min at 37 ° C with autoplasma obtained after centrifugation of blood taken from a peripheral vein into a vial with glucer, and a mixture of chemotherapeutic agents incubated under the same conditions with autoerythrothromboleomass is introduced in-house.

The invention is new, since it is not known from the level of medicine in the field of oncology in the treatment of superficial bladder cancer with chemotherapeutic agents introduced simultaneously into a natural reservoir (bladder) and systemically (intravenously). The novelty of the invention lies in the fact that in the treatment of bladder cancer, chemotherapeutic agents are administered intraperitoneally on the patient’s blood plasma, creating a depot in the area of the affected organ, and at the same time chemosanation of blood vessels with cytostatics connected to the cell suspension is performed.

The invention has an inventive step, since it is not known to an oncologist in this field and does not explicitly follow from the level of clinical oncology.

In accessible sources of information in Russia, the CIS countries and abroad, indications of a similar method for improving the immediate results of the treatment of superficial bladder cancer were not found.

The invention is industrially applicable, as it can be repeatedly reproduced and applied in healthcare, in medical institutions of a specialized profile.

The method is as follows.

TUR is performed by patients as standard.

1-1.5 months after surgery, the patient is examined for the establishment of the absence of an inflammatory process in the bladder. Then, in a patient’s morning, on an empty stomach, 100 ml of blood is taken from the ulnar vein into a standard vial with glugicir. Plasma and cell suspension of blood are obtained by sedimentation.

From 1 to 3 days of treatment, 20 mg of platinum is introduced into the bladder through a catheter, incubated for 30 min at 37 ° C with 50 ml of autoplasma; on days 4 and 5 of treatment, 50 mg of BCG vaccine, incubated for 30 minutes at a temperature of 37 ° C with 50 ml of autoplasma, which is removed from the bladder after 2 hours of exposure, is intravesical.

The cell suspension obtained after blood sampling is each time incubated with chemotherapy for 30 minutes at a temperature of 37 ° C and the patient is re-infused intravenously:

- on the 1st day - gemzar in a dose of 800 mg / m ² ;

- in the next 4 days daily - cyclophosphamide in a dose of 200 mg / m ² .

There are 3 such courses in total with an interval of 2 days, i.e. treatment takes 3 weeks.

Course doses of drugs with intravesical administration were:

cisplatin - 60 mg

BCG vaccine - 100 mg.

Course doses of drugs with intravenous administration were:

gemzar - 800 mg / m ²

cyclophosphamide - 800 mg / m ² .

To prove this, we provide an extract from the medical history confirming the clinical effect of the treatment by the proposed method.

Patient M., 57 years old, medical history No. 32658 / t, was admitted to the Department of Oncourology of the Rostov Cancer Research Institute on April 19, 2004 with a diagnosis of superficial bladder cancer. The patient complained of an admixture of blood in the urine, pain and pain during urination.

After ultrasound and cystoscopy with targeted biopsy (histological analysis No. 4594-5 of 04/20/04 - foci of transitional cell carcinoma), the diagnosis was confirmed: bladder cancer T ₁ N ₀ M ₀ , class. column 2.

A standard examination, including a chest X-ray, an ultrasound of the liver and kidneys, pathology and signs of distant metastasis were not detected. General blood test from 04/20/04 - HB 121 g / l. Er. - 4.0 × 10 ¹² / l, CPU. 0.9; Lake - 14.0 × 10 ⁹ / l, eos. - 8%, fell. - 15%, seg. - 58%, lymph. - 17%, mon. 2%, ESR 30 mm / h.

Urinalysis was not performed due to macrohematuria.

The first stage of special treatment on April 22, 04, the patient underwent transurethral resection of the bladder. The postoperative period was uneventful. The patient was discharged from the hospital in satisfactory condition. General blood test dated April 29, 04 - HB 120 g / l. Er. - 4.0 × 10 ¹² / l, CPU. 0.9; Lake - 10.0 × 10 ⁹ / l, eos. - 6%, fell. - 11%, seg. - 59%, lymph. - 20%, mon. 4%, ESR 28 mm / h.

Urine analysis according to Nechiporenko: Lake. - 10.0 × 10 ⁹ / l, Er. - 2.0 × 10 ¹² / l, cyl. - not detected.

A month after transurethral resection of the bladder on 05.24.04, the patient was admitted to the hospital again for medical treatment. No complaints, urination independent, free.

General blood test from 05.24.04: HB 120 g / l, Er. - 4.2 × 10 ¹² / l, CPU. 0.9; Lake - 5.0 × 10 ⁹ / l, eos. - 2%, fell. - 6%, seg. - 69%, lymph. - 22%, mon. - 1%, ESR 8 mm / h.

Urine analysis according to Nechiporenko: Lake - 1.2 × 10 ⁹ / l, Er - 0.5 × 10 ¹² / l, Cyl. - not detected.

From May 24, 04 to May 28, 04 in the morning on an empty stomach from the ulnar vein, the patient was taken 100 ml of blood into a standard vial with glugicir. After blood stratification, the plasma was taken under sterile conditions in a sterile vial.

In the period from May 24, 2004 to May 26, 2004, the patient was injected into the bladder through a catheter with 20 mg of platinum incubated for 30 min at 37 ° C with 50 ml of autoplasma, and on May 27, 04 and May 28, 04 d. for 2 hours, 50 mg of BCG vaccine was introduced, incubated for 30 min at 37 ° C with 50 ml of autoplasma.

The cell suspension obtained after blood sampling was each time incubated with chemotherapy for 30 min at a temperature of 37 ° C and the patient was re-infused intravenously:

- on the 1st day - gemzar in a dose of 800 mg / m ² ;

- in the next 4 days - cyclophosphamide in a dose of 200 mg / m. Then they took a break in 2 days, and from 30.05.04 to 03.06.04, another such course was conducted. Again they took a break of 2 days, and from 06.06.04 to 10.06.04, another such course.

Course doses of drugs with intravesical administration were:

cisplatin - 60 mg

BCG vaccine - 100 mg.

Course doses of drugs with intravenous administration were:

gemzar - 800 mg / m ²

cyclophosphamide - 800 mg / m.

Currently, the patient is in the dispensary without signs of relapse, with an interval of 6 months comes for follow-up examinations.

In this way, 92 patients with superficial bladder cancer were treated: 61 women and 31 men.

Of the 92 patients, 64th (69.6%) indicated therapy was carried out within 4-5 weeks after TUR, and 28 (30.4%) within 6-7 weeks. The determining point in the beginning of the proposed therapy was the absence of an inflammatory process in the bladder: the results of a urinalysis according to Nechiporenko should have been within the physiological norm.

All patients underwent treatment without complications. No signs of systemic toxicity (hematological, nephrotic) were noted in any case.

The relapse-free period in this group of patients was 3.2 ± 0.5 years.

Improving treatment results is a combination of various positive factors, namely increasing the local concentration of chemotherapy drugs associated with autoplasma, increasing the length of stay of a chemotherapy drug or immunomodulator in the area of malignant growth with simultaneous systemic exposure of chemotherapy drugs against the background of objectively reduced indicators of the general toxic effect and protective effect of autologous blood on the immune body system.

The technical and economic effect of using the "Method for the treatment of superficial bladder cancer" is the ability to improve the immediate results and quality of life of patients, increase the time of relapse-free course of the process, reduce the pathological side effects of antitumor therapy, and shorten the time for special treatment.

Claims (1)

A method of treating superficial bladder cancer, including transurethral resection, subsequent intravesical administration of chemotherapy and BCG and intravenous administration of chemotherapy, characterized in that from 1 to 3 days of treatment 20 mg of platinum are introduced into the bladder through a catheter, incubated for 30 minutes at 37 ° C with 50 ml of autoplasma, and on days 4 and 5, 50 mg of BCG vaccine is introduced, incubated for 30 minutes at 37 ° C with 50 ml of autoplasma, which is removed after 2 hours; the cell suspension obtained after blood sampling is each time incubated with chemotherapy for 30 minutes at a temperature of 37 ° C and reinfused to the patient intravenously: on the 1st day - gemzar at a dose of 800 mg / m ² , in the next 4 days daily - cyclophosphamide dose of 200 mg / m ² , such courses are carried out in total 3 with a break between them in 2 days.