RU2671403C2 - Method of combined medicinal treatment of patients with essential unresectable regional squamous ib2-iiib cervical cancer - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely, oncology, and can be used to treat cervical cancer (CC). In the preoperative period, two courses of regional chemotherapy are carried out with an interval of 3 weeks according to the following scheme: a) on the first day before and after the intra-arterial administration of cisplatin, hyperhydration is performed according to the scheme: 2.0 L 0.9 % NaCl supplemented with 20 mM KCl, solution of sodium chloride 400 ml of 0.9 % or 5 % dextrose, furosemide 40 mg (2.0), antiemetics, then intra-arterially administered cisplatin at a dose of 75 mg/m² on 400 ml of physiological solution, the administration of cisplatin is performed alternately in the right and left uterine arteries by 200.0 ml of the prepared solution at a rate of 3–4 ml/min; b) the next day, premedication is performed according to the following scheme: 12 and 6 hours before the administration of paclitaxel, 20 mg of dexamethasone is administered intramuscularly, 30–60 minutes before the administration of paclitaxel, 50 mg of diphenhydramine, 300 mg of cimetidine or 50 mg of ranitidine are intravenously administered intravenously, paclitaxel is then given intravenously at a dose of 175 mg/m² in the form of a 3-hour infusion, diluted to a concentration of 0.3–1.2 mg/ml with a solution of 0.9 % sodium chloride or 5 % dextrose solution. Invention makes it possible to create the maximum concentration of the cytostatic directly in the tumor tissue and simultaneously realize the systemic effect of chemotherapy, as a result of which resorption of the tumor takes place and the process is translated into a resectable state.

EFFECT: effect of reducing the volume of the tumor, reducing the pain syndrome and the absence of previously available blood discharges from the genital tract is achieved.

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Description

The invention relates to medicine, namely to Oncology, and can be used to treat cervical cancer (cervical cancer).

A known method of treating cervical cancer of the ib2-iii stages. Conduct remote irradiation on the pelvis in a total focal dose of 20-30 Gy. At the same time, cisplatin 30 mg is administered intravenously weekly, in a total dose of 120 mg. Perform radical hysterectomy and / or combined radiation therapy. In observations with metastases to the regional lymph nodes, they perform adjuvant chemotherapy (XT) with cisplatin 20 mg / m ² in mono mode from the 1st to the 5th day, two courses with an interval of 4 weeks (RU 2174020 C1).

However, the known method does not allow to achieve the same clinical response as our method.

A known method of neoadjuvant chemotherapy for cervical cancer neoadjuvant chemotherapy for cervical cancer. The method includes the introduction in the preoperative period of two chemotherapeutic agents. Cisplatin is administered at a dose of 75 mg / m2 and irinotecan at a dose of 180 mg / m2. The drugs are administered intraarterially, selectively catheterizing the internal iliac arteries. In total, 2 courses of regional chemotherapy are carried out with an interval of 3 weeks (RU 2405544 C1).

However, the known method does not allow to achieve the same clinical response as our method.

The technical problem is aimed at reducing the volume of the tumor, reducing pain and stopping or reducing bleeding from the external genital tract and creating favorable conditions for radical surgical treatment.

The indicated technical problem is achieved by the fact that paclitaxel in a dose of 175 mg / m ² is administered as the second chemotherapy drug, while the chemotherapy course is carried out in two stages

a) on the first day before and after intraarterial administration of cisplatin, hyperhydration is performed according to the scheme: 2.0 l of 0.9% NaCl, with the addition of 20 mmol of KCl, sodium chloride solution 400 ml of 0.9% or 5% dextrose solution, furosemide 40 mg (2.0), antiemetics, then intra-arterially injected cisplatin at a dose of 75 mg / m ² per 400 ml of physiological saline, and the introduction of cisplatin is performed alternately in the right and left uterine arteries with 200.0 ml of the prepared solution at a rate of 3-4 ml / min;

b) the next day, premedication is carried out according to the following scheme: 20 mg of dexamethasone is administered intramuscularly 12 and 6 hours before paclitaxel administration, 50 mg of diphenhydramine, 300 mg of cimetidine or 50 mg of ranitidine are administered intravenously, then intravenously paclitaxel at a dose of 175 mg / m ² in the form of a 3-hour infusion, diluted to a concentration of 0.3-1.2 mg / ml with a solution of 0.9% sodium chloride or 5% dextrose solution.

The invention is illustrated by a detailed description, clinical examples and illustrations, which depict:

FIG. 1 (a, b) - MRI of the pelvic organs of patient G., before regional chemotherapy.

FIG. 2 (a, b) - Angiography of the uterine arteries during the first chemotherapy; the catheter is superselectively positioned at the mouth of the right and left uterine arteries.

FIG. 3 (a, b) - Angiography of the uterine arteries after 21 days during the second chemotherapy, hyperplastic arteries of the cervical tumor are practically not visualized.

FIG. 4 (a, b) - MRI of the pelvic organs of patient G., after chemotherapy.

The method is as follows.

Chemotherapy is carried out in two stages:

I stage (1 day):

- before and after intraarterial administration of cisplatin, hyperhydration is performed to prevent nephrotoxicity according to the scheme: - 2.0 l of 0.9% NaCl, with the addition of 20 mmol of KCl;

- after intra-arterial infusion of the drug, 400 ml of a 0.9% sodium chloride solution or 5% dextrose solution are additionally administered;

- to maintain adequate diuresis at the end of hydration, furosemide 40 mg (2.0) is administered;

- antiemetics are administered (zofran 8 mm, 5 mg naboban, setronon 8 mg, etc.).

- cisplatin administered intraarterially at 75 mg / m ² to 400 ml of physiological saline. The introduction of cisplatin is performed alternately in the right and left uterine arteries with 200.0 ml of the finished solution at a rate of 3-4 ml / min.

The interval between courses of intra-arterial chemotherapy is 21 days.

II stage (2 day):

- premedication: 20 mg of dexamethasone i / m for 12 and 6 hours before administration (paclitaxel), 50 mg of diphenhydramine intravenously 30-60 minutes before administration and 300 mg of cimetidine or 50 mg ranitidine intravenously 30-60 minutes before administration;

- paclitaxel is administered. Paclitaxel is administered intravenously at a dose of 175 mg / m ² as a 3-hour infusion, diluted to a concentration of 0.3-1.2 mg / ml with a solution of 0.9% sodium chloride or 5% dextrose solution.

The inter-course interval is 21 days.

Then, 2 or 3 courses of chemotherapy are carried out (depending on the clinical response), followed by a follow-up examination and a decision on the further treatment option: surgery - upon achieving resectability, or palliative radiation / chemoradiotherapy while maintaining signs of unresectability, performing surgery.

A clinical example of the implementation of the proposed method.

Patient G., 54 years old. The gynecologist has been observed since 2008 (pathology according to the patient was not revealed). Since July 2015, against the background of 3 years of menopause, abundant discharge from the genital tract of a serous nature with an unpleasant odor appeared. The patient turned to the gynecologist at the place of residence, cervical cancer was suspected, a biopsy was performed. Histological examination - infiltrative squamous non-keratinized cancer. For further examination and treatment, she turned to the Moscow Scientific Research Institute of Medicine. P.A. Herzen.

According to MRI of the small pelvis (Fig. 1 a, b): the cervix is balloon-shaped, it determines the heterogeneous formation of 48 × 34 × 38 mm, extending to the posterior arch and upper sections of the vaginal wall, mainly in the right sections, on a small extent - to the anterior arch, stroma of the cervix and cervical canal practically do not differentiate. The external contours of the neck are clear, but for a short distance there is no fat layer between it and the rectum (tumor growth cannot be ruled out). There are no enlarged lymph nodes in the study area. There were no signs of parameter infiltration at the time of the study. The rest is without pathology.

In December 2015, a consultation was held. Given the prevalence of the tumor process and the impossibility of surgery, a conditionally combined treatment plan was developed with chemotherapy at the first stage using combined superselective intraarterial administration of drugs and intravenous administration of taxanes.

Neoadovatic regional chemotherapy was performed as follows.

Before and after intraarterial administration, hyperhydration was performed to prevent nephrotoxicity according to the scheme: before intraarterial administration of cisplatin, 2.0 l of 0.9% NaCl, with the addition of 20 mmol of KCl; after intraarterial infusion of the drug, 400 ml of 0.9% sodium chloride solution or 5% dextrose solution was additionally administered. To maintain adequate urine output, furosemide 40 mg (2.0) was administered at the end of hydration. Cisplatin was administered intraarterially.

The procedure for intraarterial administration of cisplatin was carried out as follows.

Access: according to the Seldinger method - the axillary artery is punctured, an introducer was installed. A Vertebral diagnostic catheter was inserted into the mouth of the uterine artery of the internal iliac artery basin along the conductor. A super selective catheter was placed in the zone of interest. Selective angiography, confirmation of the selectivity of the catheter installation (Fig. 2 a, b). Cisplatin in a dosage of 75 mg / m ^{2 is} dissolved in 400 ml of a solution of 0.9% NaCl. Next, the catheter was removed from the internal iliac artery and installed by a similar method in the counter-lateral artery (in the right and left uterine arteries). Through the Infusomat system, superselective chemoinfusion was performed at a rate of 3-4 ml / min. - 200 ml. Then the catheter and the introducer were removed, manual hemostasis was performed, and an aseptic pressure bandage was applied.

Pre-injected antiemetics (Zofran 8 mm). The interval between courses of intra-arterial chemotherapy is 21 days.

On the angiogram 21 days after the first chemotherapy (Fig. 3 a, b): a catheter is super-selectively installed at the mouth of the right and left uterine arteries. Compared with angiograms obtained during the first course of regional chemotherapy: hyperplastic arteries of a cervical tumor are practically not visualized.

The day after premedication (20 mg of IM dexamethasone 12 and 6 hours before administration, 50 mg of diphenhydramine intravenously 30-60 minutes before administration and 300 mg of cimetidine) paclitaxel is administered.

Paclitaxel was administered intravenously at a dose of 175 mg / m2 as a 3-hour infusion diluted to a concentration of 0.3-1.2 mg / ml with a solution of 0.9% sodium chloride or 5% dextrose solution. The inter-course interval was 21 days. After a specified period of time, treatment was carried out according to the above scheme.

The treatment was satisfactory.

After 3 weeks according to MRI of the pelvic organs after the implementation of regional treatment (Fig. 4 a, b): Cervix with smooth and clear contours, sizes 31 × 28 × 18 mm (previously 48 × 34 × 38 mm), myometrium structure is uniform . The rest is without pathology. Conclusion: pronounced positive dynamics in comparison with descriptive data - complete tumor resorption.

The tumor response was evaluated according to the RECIST 1.1 criteria. Complete regression of the tumor was noted.

21 days after the regional XT, the patient was admitted to the Department of Oncogynecology of Moscow P.A. Herzen, where surgical treatment is performed.

During follow-up 1 year after the combined treatment according to the method described above - tumor recurrence is not observed.

The use of the developed method in the clinic has medical and social significance, because allows you to create the maximum concentration of cytostatic directly in the tumor tissue and at the same time realize the systemic effects of chemotherapy. The objective effect of the proposed method of chemotherapy consists in resorption of the tumor and transfer of the process to a resectable state, the effect of reducing the volume of the tumor, reducing pain and the absence of previously existing blood secretions from the genital tract.

Claims (3)

A method for the combined drug treatment of patients with initially unresectable locally advanced squamous cell carcinoma of the cervix uterus IB2-IIIb, including the introduction of cisplatin at a dose of 75 mg / m ² in the preoperative period and two courses of regional chemotherapy with an interval of 3 weeks, characterized in that as the second chemotherapy drug is administered paclitaxel in a dose of 175 mg / m ² , while the course of chemotherapy is carried out in two stages: a) on the first day before and after intraarterial administration of cisplatin, hyperhydration is performed according to the scheme: 2.0 L 0.9% NaCl with the addition of 20 mmol KCl, sodium chloride 400 ml 0.9% or 5% dextrose solution, furosemide 40 mg ( 2.0), antiemetics, then intra-arterially injected cisplatin in a dose of 75 mg / m ² per 400 ml of physiological saline, and the introduction of cisplatin is performed alternately in the right and left uterine arteries with 200.0 ml of the prepared solution at a rate of 3-4 ml / min ; b) the next day, premedication is carried out according to the following scheme: 20 mg of dexamethasone is administered intramuscularly 12 and 6 hours before paclitaxel administration, 50 mg of diphenhydramine, 300 mg of cimetidine or 50 mg of ranitidine are administered intravenously, then intravenously paclitaxel in a dose of 175 mg / m ² as a 3-hour infusion diluted to a concentration of 0.3-1.2 mg / ml with a solution of 0.9% sodium chloride or 5% dextrose solution.

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