RU2367489C1 - Therapy of rectal cancer - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: therapy of rectal cancer is ensured by preoperative beam therapy "РОД" 5 Gy during 5 days, in combination with local microwave hyperthermia at temperature 42.5-43°C during 60 minutes for 3, 4 and 5 days after beam therapy sessions. A composite mixture containing sodium alginate, 2% dimethyl sulfoxide and 5-fluorouracil is introduced through rectum at exposition 6 hours in 1, 2 and 4 days prior to beam therapy sessions. For 3 and 5 days, at the same exposition, said composite mixture containing metronidazole instead of 5-fluorouracil is introduced. Further, surgical procedure follows.

EFFECT: due to selected introduction regiment of chemotherapeutical preparations as parts of the composite mixture, the method provides high concentration thereof in rectal tumours without side effect, ensures high degree of beam pathomorphism in vast majority of the patients of said category, the absence of recurrent tumour and dissemination within 3 postoperative years.

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Description

The invention relates to medicine, namely to methods for the combined treatment of colorectal cancer.

Currently, in the treatment of patients with colorectal cancer, a combined method is often used with the inclusion of preoperative radiation therapy, which allows to improve long-term treatment results (Novikova EA et al. "Preoperative irradiation of malignant tumors of the rectum." In the book of Materials of the V All-Russian Congress of Oncologists "High Technologies in Oncology", Kazan, October 4-7, 2000, volume 2, p.240-241; Berdov B.A., Yurchenko N.I. et al. "Radiation therapy in the combined treatment of colorectal cancer. - Surgery, 1989, p. 39-43). Further improvement of the combined treatment method is associated with the development of methods for selectively increasing the radiosensitivity of tumor cells to ionizing radiation. In this direction, local microwave hyperthermia is used as a radio modifier.

Among the effective radiomodifying agents that increase the sensitivity of the tumor to ionizing radiation, also include chemical compounds, in particular electron-withdrawing compounds - metronidazole and its derivatives (SP Yarmonenko in the book “Radiomodifiers in radiation therapy of tumors”, Obninsk, 1982, p. .126) and a number of antitumor chemotherapeutic agents, such as 5-fluorouracil, which is the synchronizer of the tumor cycle, and platinum, which inhibits sublethal and potentially lethal radiation injuries of tumor cells (Fight about AV et al. Proc. Proc. rep. Proc. Conf. "Radiobiological fundamentals of radiation therapy", Moscow, 19-20 April 2005, s.16-17).

The closest in technical essence and the achieved result is the “Method of combined treatment of colorectal cancer” (Yu.A. Barsukov et al., RF patent No. 2234318), including preoperative remote radiation, local microwave hyperthermia, a composite mixture with metronidazole introduced into rectum followed by surgery. The disadvantage of the prototype is the local impact on the tumor and the lack of prevention of distant metastasis.

The objective of the present invention is to provide a new, more effective method for the combined treatment of patients with primarily operable rectal cancer, which helps prevent relapses and metastases and improves patient survival. The problem is solved by the fact that a new method for the treatment of colorectal cancer is proposed, which consists in enhancing the preoperative radiation exposure of the tumor by potentiating the radiosensitizing effects obtained using three radio-modifying agents: local microwave hyperthermia, intrarectal administration of metronidazole and 5-fluorouracil in the composite mixtures followed by a radical operation.

A patient is given a radiation therapy session of ROD 5 Gy daily for five days. Local microwave hyperthermia at a temperature of 42.5-43 ° C is carried out for 60 minutes at the 3rd, 4th and 5th sessions after irradiation.

Metronidazole in the composition of the composite mixture at a concentration of 10 g / m ² is administered intrarectally before the 3rd and 5th sessions of radiation therapy with an exposure of 6 hours.

The composition of the composite mixture at the following ratios of ingredients in wt.% Contains: metronidazole 12-22, sodium alginate 4-6, dimethyl sulfoxide 2, distilled water - up to 100 (RF patent No. 2234318 "Method for the treatment of colorectal cancer").

For targeted summing of 5-fluorouracil to the rectum tumor, the above composite mixture is used, where metronidazole is replaced by 5-fluorouracil, which is administered at a concentration of 500 mg / m ² before the 1st, 2nd and 4th radiation therapy sessions with exposure 6 hours.

24-48 hours after the completion of the 5-day course of the preoperative stage, radical surgery is performed, the nature and volume of which is determined by the level of tumor localization in the rectum and the degree of its local distribution.

Scheme of the claimed method for the treatment of colorectal cancer:

RT - radiation therapy

MH - metronidazole

5FU - 5-fluorouracil

GT - local microwave hyperthermia

Examples of specific performance of the proposed method for the treatment of patients with rectal cancer

Example 1

Patient Sukhovey F.I., and / b No. 06/16521, 55 years old.

Clinical diagnosis: Cancer of the lower ampullar rectum (histologically - adenocarcinoma).

Height - 189 cm.

Weight - 92 kg.

Estimated body surface area - 2.2 m ² .

The required calculated amount of metronidazole in the composite mixture was 22 g (10 g / m ² ). The total mass of the composite mixture was 200 g.

The required calculated amount of 5-fluorouracil in the composite mixture was 1100 mg (500 mg / m ² ). The total mass of the composite mixture was 200 g.

Treatment Methodology:

1st day - intrarectal administration of a composite mixture containing 5-fluorouracil in an amount of 1110 mg calculated for this patient; a session of remote radiation therapy of ROD 5 Gy 6 hours after the introduction of the composite mixture.

2nd day - intrarectal administration of a composite mixture containing 5-fluorouracil in an amount of 1110 mg calculated for this patient; a session of remote radiation therapy of ROD 5 Gy 6 hours after the introduction of the composite mixture.

3rd day - intrarectal administration of a composite mixture containing metronidazole in an amount calculated for a given patient of 22 g; a session of remote radiation therapy of ROD 5 Gy 6 hours after the introduction of the composite mixture; a session of local microwave hyperthermia at a temperature of 42.5-43 ° C for 1 hour immediately after the completion of the irradiation session.

4th day - intrarectal administration of a composite mixture containing 5-fluorouracil in an amount of 1110 mg calculated for this patient; a session of remote radiation therapy of ROD 5 Gy 6 hours after the introduction of the composite mixture; a session of local microwave hyperthermia at a temperature of 42.5-43 ° C for 1 hour immediately after the completion of the irradiation session.

5th day - intrarectal administration of a composite mixture containing metronidazole in an amount calculated for a given patient of 22 g; a session of remote radiation therapy of ROD 5 Gy 6 hours after the introduction of the composite mixture; a session of local microwave hyperthermia at a temperature of 42.5-43 ° C for 1 hour immediately after the completion of the irradiation session.

The total focal dose of preoperative exposure was 25 Gy.

The abdominal-anal rectal resection was performed one day after the completion of the preoperative stage of treatment. The postoperative course is smooth, no complications were noted. The patient was discharged from the hospital 15 days after the operation.

Example 2

Patient Kumrova G.I., and / b No. 06/10597, 50 years old.

Clinical diagnosis: Cancer of the lower ampullar rectum (histologically - adenocarcinoma).

Height - 167 cm.

Weight - 66 kg.

Estimated body surface area - 1.7 m ² .

The required calculated amount of metronidazole in the composite mixture was 17 g (10 g / m ² ). The total mass of the composite mixture was 200 g.

The required calculated amount of 5-fluorouracil in the composite mixture was 850 mg (500 mg / m ² ). The total mass of the composite mixture was 200 g.

Treatment Methodology:

1st day - intrarectal administration of a composite mixture containing 5-fluorouracil in an amount of 850 mg calculated for this patient; a session of remote radiation therapy of ROD 5 Gy 6 hours after the introduction of the composite mixture.

2nd day - intrarectal administration of a composite mixture containing 5-fluorouracil in an amount of 850 mg calculated for this patient; a session of remote radiation therapy of ROD 5 Gy 6 hours after the introduction of the composite mixture.

3rd day - intrarectal administration of a composite mixture containing metronidazole in an amount of 17 g calculated for this patient; a session of remote radiation therapy of ROD 5 Gy 6 hours after the introduction of the composite mixture; a session of local microwave hyperthermia at a temperature of 42.5-43 ° C for 1 hour immediately after the completion of the irradiation session.

4th day - intrarectal administration of a composite mixture containing 5-fluorouracil in an amount of 850 mg calculated for a given patient; a session of remote radiation therapy of ROD 5 Gy 6 hours after the introduction of the composite mixture; a session of local microwave hyperthermia at a temperature of 42.5-43 ° C for 1 hour immediately after the completion of the irradiation session.

5th day - intrarectal administration of a composite mixture containing metronidazole in an amount of 17 g calculated for this patient; a session of remote radiation therapy of ROD 5 Gy 6 hours after the introduction of the composite mixture; a session of local microwave hyperthermia at a temperature of 42.5-43 ° C for 1 hour immediately after the completion of the irradiation session.

The total focal dose of preoperative exposure was 25 Gy.

One day after the completion of the preoperative stage of treatment, an operation was performed in the amount of trans-abdominal rectal resection. The postoperative course is smooth, no complications were noted. The patient was discharged from the hospital 16 days after the operation.

Treatment by this technique was performed in 32 patients. Within 3 years of follow-up after surgery, local relapses and distant metastases were not detected.

Technical result

The proposed method for the treatment of colorectal cancer can prevent the occurrence of locoregional relapses and distant metastases, improve the quality of life of patients. This method of treatment of colorectal cancer allows to achieve the III degree of radiation pathomorphism in 82% of patients compared with the prototype (42%). During the observation period for 3 years to date, not a single case of cancer recurrence and metastasis has been identified.

The advantages of the intrarectal method for summing 5-fluorouracil in the composition of the composite mixture:

1) the availability and ease of summing 5-fluorouracil to tumors of the rectum;

2) lack of need for constant venous access and inpatient treatment, improving the quality of life of the patient;

3) reducing the risk of complications associated with prolonged intravenous administration of 5-fluorouracil (Verso M. et al. J. Clin. Oncol. 2003; 21: 3665-75);

4) achieving a higher concentration of 5-fluorouracil in tumors with intrarectal administration compared with the use of long-term intravenous infusions. (190-210 mg / g and 140-165 mg / g, respectively).

Claims (1)

A method for the treatment of colorectal cancer by exposing a tumor to metronidazole as part of a composite mixture containing sodium alginate and a 2% solution of dimethyl sulfoxide, administered intrarectally with a 6-hour exposure, remote radiation therapy of ROD 5 Gy for 5 days, local microwave hyperthermia with a temperature of 42.5-43 ° C for 60 minutes, followed by surgery, characterized in that metronidazole in the composite mixture is administered on the 3rd and 5th days, local microwave hyperthermia is carried out on 3, 4 and 5 days after radiation therapy sessions , 5-fluorouracil in the composition of the composite mixture is administered intrarectally with an exposure of 6 hours at 1, 2, and 4 days before radiation therapy sessions.