RU2341308C1 - Method of treatment of unresectable pancreaticoduodenal cancer - Google Patents

Abstract

FIELD: medicine; oncology.

SUBSTANCE: Xeloda is introduced in dosage 850-1000 mg/m² from 1st to 16th day of treatment. Additionally platinum preparation is introduced singly on 8th day in amount 1/4-1/2 of single therapeutic dose. It is accompanied with gamma-ray therapy. Within 5 days single focal dose SFD of irradiation is 1.8-2.0 Gy. And then SFD is applied in dose 1.2-1.6 Gy twice a day until total focal dose TFD is 30-36 Gy. In 14-21 days therapy course is repeated with prescribed introduction of Xeloda within the whole course of gamma therapy until total focal dose TFD is 60-65 Gy.

EFFECT: higher degree of tumour regress, decreased radioreaction of gastrointestinal tract, improved life quality and survival time in patients suffering from severe cancers.

2 ex

Description

The invention relates to medicine, namely to oncology, and can be used in the treatment of tumors of the pancreatoduodenal region, including pancreatic cancer.

There is a method of treating unresectable pancreatic cancer (RF Patent No. 2234962, IPC A61N 5/10, publ. 2004), which consists in the following: depending on the size of the tumor, gamma-ray therapy is performed in axial rotation mode or in multi-field static exposure in two stages : first, before SOD = 24-28 Gy, and after a 2-week break before SOD = 52-54 Gy. 2-3 weeks after the end of the course of gamma therapy, autohemotherapy is carried out with the introduction of 5-fluorouracil (5-FU), doxorubicin and mitomycin C.

The proposed treatment has its drawbacks. A complex scheme for administering chemotherapy requires the use of additional equipment and specialists for blood sampling, as well as for its transfusion. In the presence of anemia and leukopenia, autohemotransfusion in a number of weakened patients and patients with symptoms of cancer intoxication may be contraindicated. Activities related to blood transfusion require strict adherence to the rules of asepsis and antiseptics, otherwise the occurrence of not only pyrogenic reactions in this group of patients with severe oncological pathology, but also the appearance of cases of the development of viral hepatitis, sepsis or AIDS is inevitable.

Closest is a method for treating pancreatic cancer based on competitive radiochemotherapy using low doses of cisplatin (Jpn. J Clin. Oncol. 2006 Aug. 36 (8) Tsujie M, Nakamori S, Tanaka E et al. Department of Surgery and Clinical Oncology , Osaka University, Suita, Osaka, Japan), including twice a day remote gamma-therapy with ROD = 1.5 Gy with an interval of 6 hours 5 days a week until SOD = 27-45 Gy. Before each gamma-therapy session, iv cisplatin was administered at a dose of 2 mg / m ² , and after the session, 5-FU iv was infused at the rate of 375 mg / m ² .

The disadvantage of this method is that this treatment regimen cannot be applied in a number of patients with concomitant pathology in the gastrointestinal tract (gastritis, peptic ulcer disease, etc.), since 5-FU negatively affects the mucosa. In addition, quite often complications from the hematopoietic system are possible, which does not allow for radiation therapy in full, and therefore, to achieve a more pronounced tumor regression.

The objective of the invention is to eliminate these drawbacks, improve treatment results in the form of reducing the size of the tumor, reducing the pain syndrome and its intensity, reducing the number and severity of local radiation reactions, as well as reducing toxic effects from chemotherapy in patients with locally advanced forms of pancreatic cancer -Duodenal zone, increased life expectancy.

For this, in a method of treating unresectable pancreatic cancer, including remote gamma therapy, chemotherapy using a platinum preparation, it is proposed to additionally prescribe xeloda 850-1000 mg / m ² from the 1st to 16th day of treatment, and to administer a platinum drug as a chemotherapy once on the 8th day in the amount of 1 / 4-1 / 2 of a single therapeutic dose simultaneously with the start of gamma therapy. Irradiation is carried out from 2-4 fields with a single focal dose of ROD of 1.8-2.0 Gy for 5 days and then with a ROD of 1.2-1.6 Gy 2 times a day until the total focal dose of SOD 30-36 Gy , after 14-21 days, repeat the course, and prescribe xeloda during the entire course of gamma therapy to a total focal dose of SOD 60-65 Gy.

The proposed combined use of these drugs and gamma therapy allows for more effective irradiation, because after the selective activation of xeloda in the tumor, based on the distribution of the enzyme thymidine phosphorylase in the human body, the sensitivity of cancer cells to radiation increases, since this enzyme is responsible for the last stage of transformation inactive xeloda in a pharmacologically active cytostatic. Thymidine phosphorylase is highly active in most solid human tumors, including tumors of the pancreatoduodenal zone, and directly correlates with the rapid growth of the tumor and its aggressive invasion. Thus, the potential activity of xeloda is highest in patients with an unfavorable prognosis, and the effect of the drug is directed to the most aggressive cancer cells. It has also been proven that 5-fluorouracil, which is formed as a result of the breakdown of xeloda directly in cancer cells, contributes to a more pronounced effect when conducting remote gamma-therapy due to synchronization of the cell cycle.

The implementation of the method shown in specific clinical examples.

Example 1

Patient K-a L.S., born in 1950, was admitted to the radiology department with a diagnosis of Pancreatic head cancer T3T1Mo. The histological structure of the tumor is adenocarcinoma.

Treatment was started with oral administration of xeloda chemopreparation at the rate of 1000 mg / m ² , which continued from the 1st to the 16th day of treatment. On the eighth day from the start of taking Xeloda, the first session of remote gamma therapy was performed on the Rocus-AM apparatus, 1 hour before which the platinum carboplatin preparation was administered at a rate of 100 mg / m ² (therapeutic dose 200-300 mg / m ² ) by intravenous infusion once (it is possible to use another drug of the platinum group in the appropriate dosage). Radiation therapy was carried out first from 2 opposite fields of 12 × 10 cm with capture of both the tumor itself and regional metastasis pathways in the area of the liver gate with ROD = 2 Gy twice a day with an interval of 4-6 hours for 5 days and then 4 tangential fields 6 × 8 cm ROD = 1.4 Gy 2 times a day to a total focal dose of 36 Gy. After a 2-week break, the course of treatment was repeated, and the administration of xeloda continued throughout the entire course of distance gamma-therapy, similarly: with single focal doses of 2.0 Gy of ROD for 5 days and then with a 1.4 Gy ROD twice a day to SOD = 65 Gy. 1 month after the end of the radical course of treatment during control computer scanning, stabilization of the tumor process was noted. At present, no relapse of the disease has been detected (after 15 months).

Example 2

Patient E-V.I., born in 1947, was treated at the Department of Radiology in 2006 with the doctor: Cancer of the biliary tract T2H1M0.

Xeloda was administered as described above. Radiation therapy was carried out on the Rocus-AM apparatus from 3 fields with ROD = 1.8 Gy 2 times a day with an interval of 4 hours between sessions for 5 days and then using the same fields with ROD = 1.2 Gy to SOD = 30 Gy After 3 weeks, the course of treatment was repeated according to the method described above to SOD = 60 Gy. During the control ultrasound, one month after the end of treatment, data on the presence of a tumor in the bile duct region were not obtained.

In the department of radiology from 2005 to 2007. treatment was performed in 14 patients with a locally advanced form of cancer of the pancreatoduodenal region of stage 3B-4A. In all patients after the 1st stage of treatment, the pain syndrome was stopped. A radical dose of 60-65 Gy was given to 9 patients (64.2%). Radiation reactions in the form of acute gastritis were detected in 3 people (21.4%), and 1 patient developed an acute radiation ulcer of the stomach at SOD = 50 Gy, which was stopped after the termination of radiation therapy and a standard drug was used during treatment peptic ulcer of the stomach. In 8 (57.1%) people, stabilization of the tumor process was noted, in 2 (14.2%) - tumor regression was more than 50%. The average life expectancy was 12.8 months (with an average life expectancy of 6-8 months from the moment of diagnosis).

The proposed method of treatment has several advantages:

- this type of treatment is well tolerated by patients due to low leuko- and neutropenia and the severity of radiation reactions from the gastrointestinal tract

- do not require special equipment and trained people,

- the applied chemotherapy drugs are not among the expensive ones.

- the degree of tumor regression allows to improve the quality of life and its duration in patients with severe oncological pathology, to reduce the time spent in hospital.

Claims (1)

A method of treating unresectable cancer of the pancreatoduodenal region, including remote gamma therapy, chemotherapy using a platinum preparation, characterized in that additionally, xeloda is prescribed as a chemotherapy on 850-1000 mg / m ² from the 1st to 16th day of treatment, and the platinum preparation is administered once on the 8th day in the amount of 1 / 4-1 / 2 of a single therapeutic dose at the same time as the start of gamma therapy, while irradiation is carried out with a single focal dose of ROD 1.8-2.0 Gy for 5 days and then ROD 1.2-1.6 Gy 2 times a day to total och oic SOD dose of 30-36 Gy in 14-21 days, repeat the course, and are assigned to receive Xeloda for the entire course of gamma-therapy to a total focal dose of 60-65 Gy SOD.