RU2586042C1 - Method of treating rectal cancer - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to oncology, and can be used in treating rectal cancer. 5-fluorouracil chemotherapy is carried out for 4-6 hours before gamma-therapy sessions enlarged fractions at 4 Gy according to dynamic dose fractionation for the first 3 days. At that, hydrogel tissue is used with 5-fluorouracil and sodium alginate “Coletex-5-ftur”, in which is added calcium sulfuric-acid in ratio 99.5-99.7 wt%: 0.5-0.3 wt%. Obtained mixture is formed in form of disc with diameter of 20-25 mm, thickness of 5-7 mm. Disc is fixed on distal end of faleic catheter. Then catheter is inserted in rectum, formed disk is located at level of tumour centre. Then air is fed into catheter cylinder till its complete filling and fixing in intestinal lumen. Catheter is removed before session of gamma-therapy.

EFFECT: method provides manifested regress of primary tumour that enables further carry out organ-preserving radical surgical intervention.

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Description

The invention relates to medicine, namely to oncology, and can be used in the treatment of colorectal cancer.

The successes of modern oncology have made it possible to improve the results of treatment of patients with rectal cancer, however, this problem remains relevant due to the constant increase in the incidence of this pathology and the neglect of most newly diagnosed cases. At the time of diagnosis, at least 10-15% of patients are considered inoperable due to the spread of the tumor into surrounding organs and tissues. Despite the improvement of surgical technique, the five-year survival rate and local recurrence after only surgical treatment of colorectal cancer does not change and ranges from 10-12%.

A known method of treating colorectal cancer (RF Patent No. 2424011, IPC A61K 31/10, publ. 2011). The method includes the intrectal administration of 5-fluorouracil and metronidazole as part of a composite mixture containing sodium alginate and a 2% solution of dimethyl sulfoxide, remote radiation therapy, local microwave hyperthermia, followed by surgery. In this case, 5-fluorouracil is administered from 1 to 5 days daily, and on the 3rd and 5th days of the course of treatment, 5-fluorouracil is administered in combination with metronidazole with an exposure of 5 hours, and surgery is performed 2-3 weeks after the end of the course of treatment.

The disadvantage of this method is the following: when the tumor is localized in the anal canal or in the ampullar region, it is impossible to bring a mixture of drugs because of problems with fixing it in this anatomical region. This type of administration of drugs in the form of a composite mixture cannot contribute to their uniform and long-term effect on the tumor.

Closest to the proposed method is a method for the treatment of colorectal cancer (RF Patent No. 2398608, IPC A61K 31/513, publ. 2010), including chemotherapy with 5-fluorouracil (5-FU), gamma therapy according to a dynamic dose fractionation scheme with enlarged fractions of 4 Gy for the first 3 days, and then small fractions in hyperfraction mode 2 times a day with an interval of 4-5 hours of 1.25 Gy to a total focal dose of 47.0 Gy. In addition, derinat gel is introduced in the form of microclysters at night for the first 5 days of treatment of 5-10 ml, when irradiated with large fractions of 10-20 ml, when irradiated with small fractions of 30-35 ml, after the end of the irradiation course of 25-30 ml for 2 weeks.

The disadvantage of this method is the inability to achieve the maximum local effect of the drug on the tumor tissue, which does not allow to achieve a high concentration of the drug in the tumor and does not lead to a pronounced antitumor effect.

The objective of the invention is to eliminate these disadvantages, increase the effectiveness of treatment and its tolerance by reducing the toxic reactions of 5-FU in the body, while a high concentration of the drug in the tumor.

To solve the problem in the treatment of colorectal cancer, including chemotherapy with 5-fluorouracil, gamma-therapy according to the scheme of dynamic dose fractionation with enlarged fractions of 4 Gy for the first 3 days, and then in small fractions, it was suggested that chemotherapy be carried out before gamma-therapy sessions in coarse fractions for 4-6 hours, while using a hydrogel napkin with 5-fluorouracil and Koleteks-5-ftur sodium alginate, to which calcium sulfate is added in the ratio of 99.5-99.7 wt. %: 0.5-0.3 mass. % Then it is necessary to form the resulting mixture in the form of a disk with a diameter of 20-25 mm, a thickness of 5-7 mm, which is fixed at the distal end of the Faleevsky catheter. After that, a catheter is inserted into the rectum, a formed disk is placed at the center of the tumor, then air is fed into the catheter balloon until it is completely filled and tightly fixed in the intestinal lumen, the catheter should be removed before the start of the gamma-therapy session.

The proposed method of treatment allows you to bring the drug directly to the tumor and to achieve a high concentration of the drug in the local-regional blood pool of the tumor. Local exposure to 5-fluorouracil can reduce its overall toxic effect on the body and, as a result, improves the results of treatment of patients with common forms of colorectal cancer due to the summation of the effect of local exposure to 5-fluorouracil and radiation therapy, which allows to reduce the volume and linear size of the primary tumor .

This addition of 5-fluorouracil allows you to limit the area of drug intake, because in the case of disk formation, the wipes do not spread over the injection zone, it can be fixed on the lesion, the medicine is supplied and released in a directional manner.

The method is carried out in the following way.

According to the above methodology, a preparation is prepared on the basis of 5-fluorouracil, sodium alginate and calcium sulfuric acid in a ratio of 99.5-99.7 mass. %: 0.5-0.3 mass. % and form the resulting mixture in the form of a disk. 4-6 hours before the start of radiation therapy, a Faley catheter is inserted into the rectal ampoule under visual control using a rectoscope, to the cuff of which a manufactured disk is attached using medical glue.

After extracting the rectoscope, the drug is tightly fixed in the center of the tumor by inflating the cuff with air until it is completely expanded, which is fed through an additional catheter channel. The exposure is 4-6 hours, after which the catheter is removed from the rectum.

Gamma therapy is carried out according to the scheme of dynamic dose fractionation with enlarged fractions of 4 Gy for the first 3 days on the remote gamma therapy unit or during brachytherapy.

Next, gamma therapy is carried out in small fractions according to a standard method to SOD = 30-34 Gy.

Example 1

Patient K., 48 years old, was admitted to the radiology department on 03/19/15 with a diagnosis of cancer of the lower and middle ampulla of the rectum T3HxMo. Histology is a highly differentiated adenocarcinoma. After a clinical examination, the patient was treated according to the proposed method: a course of radiation therapy was carried out from 4 fields in the regime of dynamic dose fractionation with ROD = 3.6 Gy for the first 3 days and then with ROD = 2.4 Gy to SOD = 34.0 Gy for 11 days excluding Saturday and Sunday.

6 hours before the start of the radiation therapy session, 5-fluorouracil was locally fixed in the first 3 days by the proposed method. Previously, calcium sulfate in the amount of 0.015 g was added to a hydrogel napkin with 5-fluorouracil and Coletex-5-ftur sodium alginate in the amount of 2.985 g, the resulting mixture was formed in the form of a disk with a diameter of 20 mm and a thickness of 5 mm. According to the proposed method, the disk was brought to the tumor, fixed using the cuff of the Faleevsky catheter.

Local radiation reactions, toxic manifestations and hemodynamic disturbances throughout the course of treatment have not been identified. The patient was discharged from the ward in satisfactory condition. After 17 days, she underwent a radical operation in the form of abdominal-anal resection in a specialized hospital. Data for relapse and metastases were not received. There are no late radiation complications.

Example 2

Patient C, 51, was admitted to the department on 12/16/14 with a diagnosis of Cancer of the lower ampullar section of the rectum T4HxMx. Condition after application of an unloading colostomy 10.11.14 regarding partial intestinal obstruction. Histology is a middle differentiated adenocarcinoma.

After clinical follow-up, the department conducted a preoperative course of chemoradiotherapy according to the scheme: gamma therapy according to the dynamic dose fractionation scheme with enlarged fractions, which were administered during brachytherapy with ROD = 3 Gy every other day # 3 to SOD = 9 Gy and then gamma therapy in small fractions with ROD = 2 Gy to SOD = 32 Gy on the background of local administration of 5-FU 500 mg in the first 3 days of brachytherapy 4 hours before the start of the session. For this, calcium sulfate in the amount of 0.0105 g was added to the hydrogel napkin with 5-fluorouracil and Coletex-5-ftur sodium alginate in the amount of 3.4895 g, the resulting mixture was formed in the form of a disk with a diameter of 25 mm and a thickness of 7 mm

Chemotherapy was carried out against the background of antiulcer and corrective infusion and antibiotic therapy, taking into account the patient's condition and his medical history. Radiation reaction at the end of treatment in the form of moderate cystitis, which did not need drug correction. Initially, the patient was examined by a proctologist surgeon: the case was declared inoperable. 25 days after the end of the 1st stage of radiation therapy, the patient was operated on in the amount of abdominal-perineal extirpation of the rectum and resection of the soft tissues of the right buttock.

In this way, treatment was performed in 25 patients with colorectal cancer of various localization and degree of tumor differentiation. All patients, 3-4 weeks after the end of the course of chemoradiotherapy, underwent radical surgery in the amount of anterior resection or abdominal-perineal extirpation of the rectum. During the observation of relapses and distant metastases in this group of patients was not detected.

This treatment regimen is based on clinical, radiobiological and practical data. As clinical studies have shown, the use of this treatment regimen allows one to achieve pronounced regression of the primary tumor in patients with this severe oncological pathology, and subsequently carry out organ-preserving radical surgical interventions, which is also well tolerated by patients.

Claims (1)

A method for the treatment of colorectal cancer, including chemotherapy with 5-fluorouracil, gamma-therapy according to a dynamic dose fractionation scheme with enlarged fractions of 4 Gy for the first 3 days, and then small fractions, characterized in that chemotherapy is carried out before enlarged gamma-therapy sessions fractions for 4-6 hours, while using a hydrogel napkin with 5-fluorouracil and Coletex-5-ftur sodium alginate, to which calcium sulfate is additionally added in a ratio of 99.5-99.7 wt. %: 0.5-0.3 mass. %, the resulting mixture is formed in the form of a disk with a diameter of 20-25 mm, a thickness of 5-7 mm, which is fixed at the distal end of the Faley catheter, a catheter is inserted into the rectum, a formed disk with a chemotherapeutic drug is placed at the level of the tumor center, air is fed into the catheter balloon its full filling and tight fixation in the lumen of the intestine, and the catheter is removed before the start of the gamma-therapy session.