RU2414936C1 - Method of treating rectal cancer - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly oncology, and can be applied in treating rectal cancer. A method involves radiation teletherapy, drug therapy (capecitabine, oxaliplatin), local UHF hyperthermia, metronidazole as a part of a composite mixture introduced through rectum, and following surgery. Capecitabine is introduced orally in dose 650 mg/m² during the whole course of radiation therapy every 12 hours, oxaliplatin is administered on the 2nd, 9th, 16th days of treatment intravenously in dose 50 mg/m². Local UHF hyperthermia precedes a radiation session on the 8th, 12th, 15th, 17th days of treatment. Radiation is executed at 4 Gy of single basic dose three times a week every 48 hours for 22 days, 40 Gy of total basic dose. Metronidazole as a part of a polymeric composition is introduced on 12th and 17th days of treatment before UHF hyperthermia sessions with exposition 5 hours. The treatment is carried out with underlying protection of surrounding tissues with gas hypoxic mixture GHM-9.

EFFECT: use of the invention allows reaching tumour regress and executing radical surgery due to a synergic effect of the components and an intensified therapeutic effect ensured by implemented mechanisms of radio- and chemosensibilisation.

2 cl, 2 ex

Description

The invention relates to medicine, namely to Oncology, and can be used to treat locally advanced rectal cancer.

To locally advanced rectal cancer include motionless and sedentary tumors, growing into neighboring structures, when the implementation of radical surgery is impossible. Treatment of locally advanced colorectal cancer is carried out by a combined method using preoperative local radiation therapy to reduce the volume of tumor formation and subsequent radical surgery.

The improvement of the combined treatment is associated with the development of methods for the selective increase in the radiosensitivity of tumor cells to ionizing radiation. For this purpose, radio modifiers are used - various physical and chemical factors that have this ability. As radio modifiers, local microwave hyperthermia and antitumor drugs, such as 5-fluorouracil, which is a tumor cycle synchronizer, are used; platinum compounds capable of inhibiting sublethal and potentially fatal radiation injuries of tumor cells (Danielle Fm De Haas-Kock et al. Concomitant hyperthermia and radiation therapy for treating locally advanced rectal cancer. Cochrane Database Syst Rev: CD006269, 2009; Pasetto LM et al., Neoadjuvant chemoradiotherapy with 5-fluorouracil by bolus. Anticancer Res. 2008 Nov-Dec; 28 (6B): 4095-100; Gerard J, Conroy T, Bonnetain F, et al: Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3- 4 rectal cancers: Results of FFCD 9203. J Natl Cancer Inst 24: 4620-4625, 2006).

A known method of treatment of XELOX-RT, including the use of radiation therapy with SOD 50 Gy, fractions of 2 Gy, chemotherapy drugs capicitabine, oxaliplatin. The disadvantages of this method include the inadequate effect of combined treatment on the tumor, which does not in all cases make it possible to transfer it to an operable state (Claus Rödel et al., Multicenter Phase II Trial of Chemoradiation With Oxaliplatin for Rectal Cancer, 2007).

The prototype is a method of treating colorectal cancer (USSR author's certificate No. 1540072 of 09/18/1987), which includes the intrarectal administration of metronidazole with simultaneous local microwave hyperthermia followed by radiation and surgical intervention.

However, the use of this method of treatment does not lead to pronounced regression of the tumor to perform radical surgery.

The objective of the invention is the creation of a new, more effective method for the combined treatment of locally advanced colorectal cancer, the use of which will allow for pronounced regression of the tumor to perform radical surgery.

The problem is solved in that a new method is proposed for the treatment of colorectal cancer by exposing the tumor to remote radiation therapy, local microwave hyperthermia, metronidazole as part of a composite mixture administered intrarectally, capecitabine administered orally throughout the course of radiation therapy, oxaliplatin administered intravenously , the use of a hypoxic gas mixture containing 9% oxygen and 91% nitrogen (GHS-9) to protect surrounding tissues from exposure to radiation with subsequent surgical intervention. When used together, these agents have a synergistic effect and enhance the therapeutic effect due to the implementation of the mechanisms of radiosensitization and chemosensitization and synergism of radiosensitizing agents. After completing the course of preoperative treatment, surgery is performed after 6-8 weeks.

The method is as follows.

Radiation therapy of 4 Gy, SOD 40 Gy (total 10 sessions) is given to the patient within 22 days 3 times a week after 48 hours.

Local microwave hyperthermia is carried out before the irradiation session for 8,12,15 and 17 days of treatment on the Yacht-4 apparatus in the mode of microwave waves with a frequency of 460 MHz at a temperature of 42.5-43 ° C for 60 minutes.

Capecitabine is administered orally at a dose of 650 mg / m ² 2 times a day throughout the course of radiation therapy.

Oxaliplatin is administered intravenously once a week at a dose of 50 mg / m ² for 3 weeks.

Metronidazole in the composition of the composite mixture at a concentration of 10 mg / m ² is administered intrarectally on days 12 and 17 of treatment before microwave hyperthermia sessions with an exposure of 5 hours. The composition of the composite mixture in the following ratios of ingredients in wt.% Contains: metronidazole 12-22, sodium alginate 4-6, dimethyl sulfoxide 2, distilled water to 100 (RF patent No. 2352359 "Method for creating a composition for drug delivery to the body cavity in diseases" ) After the completion of the irradiation course, after 6 weeks, surgery is performed, the volume of which is determined by the location of the tumor in the rectum and the severity of its regression as a result of the application of the proposed method of treatment.

Clinical examples of the proposed method:

Example 1

Patient A., 62 years old, and / b No. 08/19581.

Diagnosis: locally advanced cancer of the lower ampulla of the rectum with germination in the vagina T 4 Nx Mo.

Histological diagnosis: moderately differentiated adenocarcinoma.

Received complaints of stool disorders, the appearance of blood and mucus in the feces, pain in the anus. The tumor was determined at a height of 5 cm from the transitional fold, limited mobility, circularly narrowing the lumen of the intestine, infiltrating the posterior wall of the vagina, protruding into the lumen of the vagina by 4-5 cm. According to MRI, the size of the tumor was 10.2 × 7.4 cm. fiber was determined by multiple enlarged lymph nodes up to 2.5 cm in diameter. According to irrigography, the extent of the lesion was 10 cm.

Irradiation was carried out 3 times a week, after 48 hours for 22 days, ROD 4 Gy, SOD 40 Gy. During the entire course of radiation therapy, the patient received oral capecitabine at a dose of 650 mg / m ² with an interval of 12 hours. Microwave hyperthermia was performed before irradiation sessions on the 8th, 12th, 15th and 17th days of treatment. Oxaliplatin was administered intravenously at a dose of 50 mg / m ² on days 2, 9, 16 of treatment. Metronidazole was administered as a composite mixture at a dose of 10 mg / m ² on days 12 and 17 of treatment before microwave hyperthermia sessions. Metronidazole exposure was 5 hours. The treatment was carried out against the background of the protection of the surrounding tissues using a gas hypoxic mixture GHS-9.

Side effects: leukopenia of the 1st degree, radiation epithelitis of the perineum of the 1st degree.

The treatment was carried out in full.

After completing the course of preoperative combined treatment, the patient was examined. According to MRI, the tumor decreased by more than 2 times, its size was 4.5 × 3.8 cm. According to irrigography, the extent of the lesion was 5 cm.

Surgical intervention - abdominal-anal resection of the rectum with resection of the posterior wall of the vagina - was performed 6 weeks after the end of preoperative treatment. There were no complications in the postoperative period. Histological examination of the surgical material revealed areas of severe fibrosis without signs of tumor growth. A complete regression of the tumor, stage 4 of therapeutic pathomorphism was ascertained. Of the 7 seals of adipose tissue, 2 lymph nodes were found without elements of tumor growth. The patient was discharged from the hospital 15 days after the operation.

Example 2

Patient B., 62 years old. IB No. 09/7606.

Diagnosis: locally advanced cancer of the middle ampullar part of the rectum T4N × Mo.

The histological diagnosis is moderately differentiated adenocarcinoma.

He entered the department with complaints of violation of the stool, the appearance of blood and mucus in the feces. The tumor was determined at a height of 7 cm from the transitional fold, circularly narrowing the lumen, motionless. In connection with the complete immobility of the formation, it was decided to conduct a course of treatment of locally advanced rectal cancer. According to MRI, the size of the tumor was 6.2 × 7.4 cm. According to irrigography, the extent of the lesion was 7 cm.

Irradiation was carried out 3 times a week, after 48 hours for 22 days, ROD 4 Gy, SOD 40 Gy. During the entire course of radiation therapy, the patient received oral capecitabine at a dose of 650 mg / m ² with an interval of 12 hours. Microwave hyperthermia was performed before irradiation sessions on days 8, 12, 15, 17 of treatment. On days 2, 9, and 16, oxaliplatin was administered intravenously at a dose of 50 mg / m ² . Metronidazole in the composition of the composite mixture at a dose of 10 mg / m ² was administered on the 12th and 17th days of treatment before the sessions of microwave hyperthermia. Metronidazole exposure was 5 hours. The treatment was carried out against the background of the protection of the surrounding tissues using a gas hypoxic mixture GHS-9.

Side effects: leukopenia of the I degree. The treatment was carried out in full.

Evaluation of the effect was carried out 6 weeks after the end of the course of preoperative combined treatment. According to MRI, tumor formation in the pelvis was no longer detected. According to irrigography, “rectification” of the walls of the rectum was determined over 5.2 cm.

Surgical intervention - abdominal-anal resection of the rectum - was made 6 weeks after the end of preoperative treatment. No complications were observed. Histological examination of the surgical material revealed areas of marked fibrosis with single foci of tumor growth. The 3rd degree of therapeutic pathomorphism was ascertained.

The patient was discharged from the hospital 15 days after the operation.

The technical result.

The inventive method for the treatment of colorectal cancer allows for pronounced regression of the tumor and perform radical surgery. Treatment using this method was performed on 33 patients. Radical surgical interventions were performed in 31 patients (93.9%). Tumor regression of more than 30% was observed in 29 patients (87.8%).

Claims (2)

1. A method for the treatment of colorectal cancer by exposing the tumor to remote radiation therapy, local microwave hyperthermia, metronidazole in the composition of a composite mixture administered intrarectally, followed by surgery, characterized in that capecitabine is administered orally at a dose of 650 mg / m ² for the entire course of radiation therapy with an interval of 12 hours, oxaliplatin is administered on 2, 9, 16 days of treatment intravenously at a dose of 50 mg / m ² once a week for 3 weeks, local microwave hyperthermia is carried out before the irradiation session at 8, 12, 15 , 17 days of treatment, about bloating is carried out 3 times a week after 48 hours for 22 days; metronidazole in the composition of the composite mixture is administered on days 12 and 17 of treatment before sessions of microwave hyperthermia with an exposure of 5 hours 2. A method of treating colorectal cancer according to claim 1, characterized in that the treatment is carried out against the background of the use of a hypoxic gas mixture GHS-9.