A method for the treatment of irresectable pancreatic cancer

 

The invention relates to medicine, namely to Oncology, and can be used in various types of cancer of the pancreas. Conduct remote gamma-therapy on the pancreas in the individual mode: when a small tumor sizes - dual-axis or single-axis two-sector rotation, and when the size of the tumor more than 10 cm in static multi-field mode with fractional summed dose: 2 G 2 times a day with an interval of 4-5 hours. Total focal dose (SOD) 24-28 Gr. Course resume after a two-week break before SOD 52-56 Gr. 2-3 weeks are autohemotherapy: take blood in 80 ml 3 vials with standard preservative, the first day of the first vial Autocraft injected with 5-fluorouracil based 600 mg/m2the second vial - doxorubicin 30 mg/m2the third vial - mitomycin C 10 mg/m2, incubated them at 37 C for 45 minutes and make reinfuse blood with cytotoxic drugs in sequence. On the 8th day take 80 ml of the patient's blood in a vial with preservative injected into the vial 5-fluorouracil 600 mg/m2, incubated for 45 minutes at 37 With and administered to the patient. On the 27th day of the administered 5-fluorouracil 600 mg/m2the second vial - doxorubicin 30 mg/m2, incubated at 37 With over 45 minutes and is re-infused in the specified sequence. On the 36th day collect the patient's blood in the amount of 80 ml in a bottle with a standard preservative in the vial is administered 5-fluorouracil at a dose of 600 mg/m2, incubated for 45 minutes at 37 With and administered to the patient. Course doses of chemotherapy are: mitomycin C 10 mg/m2, doxorubicin 60 mg/m25-fluorouracil - 2400 mg/m2. The method allows to reduce the size of the tumor, enhance analgesic effect, reduce the frequency of complications of radiation and chemotherapy. 2 Il.

The invention relates to medicine, namely to Oncology and can be used with irresectable pancreatic cancer cancer: epithelial, small cell lung, malignant insuloma, adenocarcinoma, cancer of unknown histological structure, when expressed pain syndrome.

Known "Method of treatment of unresectable pancreatic cancer" (see Barkanov A. I. Radiation therapy of patients with unresectable pancreatic cancer guidelines. M., 1988, page 18). the Alamosa through 0.5-1 month. Treatment carried out by bremsstrahlung 15-25 MeV, which is directed along the long axis of the gland and forms the dose field, which includes the pancreas, regional lymph nodes and foci of tumor invasion. When combined with radiation therapy 2/3 of the total focal dose (SOD) is supplied through the brake, and 1/3 due to electron radiation. In the absence of high-energy accelerators used remote gamma-therapy through the lattice diaphragms with 2 counter-directed anterior and posterior fields with shielding the spinal cord. Single focal dose (ROD) under the open areas of the lattice 4-5 Gr, SOD 60-70 Gy in palliative and 100-120 Gr - a more radical plan. When epithelial, small cell lung cancer, malignant insuloma SOD 55-60 Gy, with adenocarcinoma of 60-70 Gy at the tumor unknown histological structure, if the operation proved its malignant nature (there are metastases and germination), you must wrap SOD 60-70 Gy, because pancreatic cancer in most cases is an adenocarcinoma. Metastases in the peripheral, allocatelli lymph nodes, solitary liver metastases is irradiated by a dose of 65-70 Gy. In this method, the treatment of radiation reaction KABLUEY, 13% - change treatment plan. Pain occurs at the end of 17.5 G, disappearance - at 42 Grams life expectancy at SOD 15-30 Grams is 8 months, 50-60 Gr - 17.6 months, 60-70 Gy - 17.5 months, 70-80 Gr - 25.7 months. The worst results are seen in patients in a serious condition, large (up to 12 months) interval between surgery and irradiation - 8 months, expressed painful syndrome - 11.7 months, the metastasis of a cancer in the left lobe of the liver - 9.5 month.

Taking into account the indications and contraindications in the treatment of inoperable pancreatic cancer, the results demonstrate the feasibility of radiotherapy. However, the treatment is accompanied by local radiation reaction in the skin, the mucous membrane of the stomach, nausea, vomiting, require interruption of the irradiation, radiation anastomosis, enteritis, in which drugs it is advisable to enter parenteral, due to malabsorption in the intestine. In severe General condition, observed in 25% of patients, radiation therapy is usually ineffective.

Thus, the disadvantages that accompany exposure irresectable pancreatic cancer, require further improvement of treatment.

nerasprostraneniyem pancreatic cancer", Suslov N. L., Sholinsky C. N., Murawski, C., Okeanov N. And., Smack A. I., I Congress of oncologists of CIS 3-6 December 1996, , Moscow, Association of Oncology, radiology and x-ray centers and institutes of the CIS, pages 342-343), chosen as a prototype. Treatment begins after applying biliodigestive anastomosis and includes remote gamma-therapy (DHT) and 6 courses of chemotherapy. DHT is until SOD 70 Gy to split the course or major factions. Chemotherapy is carried out by PAP-pattern: 5-fluorouracil 300 mg/m2in 1-5 days, adriablastin 50 mg/m2in the 1st and cisplatin 20 mg/m2in 1-5 days. Radiation and chemotherapy is carried out under the protection of the body by a complex of vitamins a, C, and E. After completion of radiation therapy all patients observed analgesic effect, which allows you to refuse drug and in most cases from non-narcotic analgesics. However, the treatment is accompanied by local radiation reaction. RAR-chemotherapy, although effective, however, it has a high toxicity. In 35.7% of cases of leukopenia was the cause of the failure from chemotherapy or dose reduction of chemotherapy. The main doselimiting factor is mielodeprescia.

In addition the CSO treatment of pancreatic cancer according to the described scheme.

The aim of the invention is to improve the immediate results, manifested in the reduction of the sizes of irresectable pancreatic tumor, analgesic effect and reduce complications that accompany radiation therapy and chemotherapy - high toxicity, General and local radiation reaction, which allows to treat the entire cohort of patients with irresectable pancreatic cancer.

This goal is achieved by the fact that after a diagnostic laparotomy or palliative surgery and the impossibility of radical operations are performed DHT on the pancreas with irresectable tumor with subsequent autohemotherapy. Remote gamma-therapy in the individual mode, depending on the tumor size and extent of the process, the small size of the tumor biaxial or uniaxial sector rotation, and static multi-field mode when the size of the tumor more than 10 cm, single focal dose of 4 Gy fractionally, 2 times daily 2 Gy with an interval of 4-5 hours, up to a total focal dose 24-28 Gr course resume after a 2-week break before summing the total focal dose 52-56 Gr. After 2-3 weeks spend autohemotherapy2in the second vial, a solution of doxorubicin 30 mg/m2the third vial a solution of mitomycin C 10 mg/m2; the vials incubated at T +37C for 45 minutes and blood is re-infused with cytotoxic drugs to the patient in a specified sequence, in the twenty-seventh day administered 5-fluorouracil and doxorubicin, in the eighth and 36th days administered 5-fluorouracil, all drugs administered, according to the above method; the total course dose of 5-fluorouracil - 2400 mg/m2, doxorubicin 60 mg/m2, mitomycin C 10 mg/m2.

The invention of "a Method for the treatment of irresectable pancreatic cancer" is new, because it is unknown the level of medicine in the treatment of patients with irresectable tumors of the pancreas in severe condition, when expressed pain syndrome.

The novelty of the invention lies in the fact that after a diagnostic laparotomy or palliative surgery and the inability to perform radical surgical treatment of distant gamma-therapy of the pancreas with irresectable tumor in the individual mode, dual-axis or single-axis two-sector rotation with small tumor size in static multi-field mode when Ratsa the main feature and allows you to bring high single focal dose and positively affect the objectivity of treatment in a small number and severity of radiation reactions. Total focal dose adjusted to 24 Gy, followed by a 2-week break. After a 2-week break, bring the total focal dose to 52-56 Gr that the biological effect is similar 60-68 Gy in conventional fractionation. 2-3 weeks is autohemotherapy (5-fluorouracil, doxorubicin, mitomycin C): on the first day you enter 5-fluorouracil, doxorubicin, mitomycin C, eighth and thirty-sixth 5-fluorouracil, in the twenty and seventh - 5-fluorouracil and doxorubicin. Course doses of chemotherapy are: mitomycin C 10 mg/m2, doxorubicin 60 mg/m2a 5-foretell - 2400 mg/m2. The patient is venipuncture, is the blood sample into the vial with the standard preservative. The blood is drawn in the amount of 240 ml 3 vials with 80 ml. In the first vial Autocraft injected with 5-fluorouracil based 600 mg/m2the second bottle is the solution of doxorubicin at a dose of 30 mg/m2the third bottle is a solution of mitomycin C in the dose of 10 mg/m2. Next, the vials are incubated at 37 C for 45 minutes, and then you reinfuse blood with cytotoxic drugs in sequence. The subsequent introduction of chemotherapy are carried on anal is the possibility to decrease the incidence of tumors of the pancreas, to reduce complications of radiation and chemotherapy - high toxicity, mielodepressiu provides a course of treatment without interruption about complications.

The invention of "a Method for the treatment of irresectable pancreatic cancer is industrially applicable, as may be used in health care, cancer research institutes, breast care clinics and other medical institutions for the treatment of cancer patients.

"A method for the treatment of irresectable pancreatic cancer" is as follows. 10-14 days after diagnostic laparotomy or palliative surgery begins remote gamma-therapy on the pancreas. Topometric training is conducted with the help of ultrasound scanning, x-ray computed tomography, and the imposition of radiopaque clips on the periphery of the tumor and cancer. The irradiation is carried out on the device "Rocus M". Given the frequent (25%) development of multicenter cancer, as well as the total destruction of the pancreas (40%), in the area of radiation exposure included all iron. With a small tumor size method is used with a two-axis is sadosi to the configuration of the pancreas with maximum sparing surrounding healthy tissues. When the tumor size greater than 10 cm, irradiation begins in static multi-field mode with a subsequent mode change by decreasing tumor size.

Single focal dose of 4 Gy is supplied fractionally, 2 G, 2 times a day with an interval of 4-5 hours. This methodology allows us to bring high single focal dose and positively affect the objectivity of treatment in a small number and severity of radiation reactions, can reduce the duration of treatment. After summing up the total focal dose 24-28 G is a break of 2 weeks, after which radiation therapy is resumed until the sum total focal dose 52-56 Gr that the biological effect is similar 60-68 Gy in conventional fractionation.

2-3 weeks is autohemotherapy (5-fluorouracil, doxorubicin, mitomycin C): on the first day you enter 5-fluorouracil, doxorubicin, mitomycin C, eighth and thirty-sixth 5-fluorouracil, in the twenty and seventh - 5-fluorouracil and doxorubicin. Course doses of chemotherapy are: mitomycin C 10 mg/m2, doxorubicin 60 mg/m2, 5-fluorouracil - 2400 mg/m2. The patient is venipuncture, is the blood sample into the vial with the standard preservative (us is macroview injected with 5-fluorouracil based 600 mg/m2. The second bottle is the solution of doxorubicin at a dose of 30 mg/m2. The third bottle is a solution of mitomycin C in the dose of 10 mg/m2. Next, the vials are incubated at 37 C for 45 minutes, and then you reinfuse blood with cytotoxic drugs in sequence. On the 8th day take 80 ml of the patient's blood in a vial with preservative injected into the vial 5-fluorouracil 600 mg/m2, incubated autochrome with cytostatic for 45 minutes at 37 With and administered to the patient. On the 28th day collect 160 ml of blood of the patient in 2 bottles with standard preservative 80 ml in each vial. In the first vial is injected with 5-fluorouracil 600 mg/m2on the second bottle is the solution of doxorubicin at the rate of 30 mg/m2. The vials are incubated at 37 C for 45 minutes, and the blood with dissolved chemicals reinfused in sequence. On the 36th day is the blood of the patient in the amount of 80 ml in a bottle with a standard preservative; in a bottle with Autocraft administered 5-fluorouracil at a dose of 600 mg/m2, incubated for 45 minutes at 37 With and administered to the patient.

When the history of the disease.

Example 1. Patient B., 1937 birth, medical history, No. 12793/n, enrolled in thoracoabdominal Department of the Rostov cancer research Institute 09.09.01 years with symptoms of obstructive jaundice. The first stage of surgical treatment 10.09.01, conducted operation cholecystostomy; revision of the abdominal cavity revealed a tumor of the pancreas. The patient was discharged for edema effects of obstructive jaundice and possible subsequent radical surgery.

10.11.01 year reentry in thoracoabdominal Department of the Rostov cancer research Institute. Upon receipt of the phenomenon of obstructive jaundice are missing, however, patients concerned about persistent epigastric pain, worse with exercise, weight loss of 10 kg in 2 months, lack of appetite, weakness. 12.11.01 year the patient is taken to the second stage of surgical treatment. At laparotomy revealed a pancreatic tumor size of about 6x6 cm, dense, hilly, germinating celiac trunk and vessels hepatoduodenal ligaments, metastatic lymph nodes in the upper and lower edge of the pancreas. Case recognized presettable what they sostem.

Histological analysis obtained by biopsy of the lymph node response received - metastasis adenocarcinoma (histological analysis No. 624379).

The postoperative period was unremarkable. 26.11.01 year the patient was transferred to the radiology Department of the Rostov cancer research Institute. When inspecting the condition of moderate severity. Tongue coated white bloom. The abdomen is soft, moderately painful in the postoperative scar. During deep palpation in the epigastric region is dense, painful extensive education up to 8 cm in diameter. The Karnofsky Index Of 20-30%.

26.11.01, performed ultrasound examination of abdominal cavity organs (Fig.1). On the sonogram pancreas is enlarged, heterogeneous echostructure. In the projection head and body of the pancreas hypoechoic education dimensions of 7.55.6 cm, the blood supply to tumors of the peripheral avascular.

In General, the analysis of blood from 26.11.01,: hemoglobin 112 g/l, erythrocytes-3,91012colour index of 0.85, leukocytes 4,1109, leukocyte formula: stab - 5%, segmentate/l, urea 4.0 mmol/l, total protein 66 g/l, bilirubin free 11 mmol/l, the bound is not specified, creatinine 109 mmol/l, amylase 9,8 ED, alanine aminotransferase 1.2 mmol/l, alkaline phosphatase 41,2 ED, thymol test 1 ED.

Patients received remote gamma-therapy on the pancreas in Twinax mode rotation apparatus Rocus M 27.11.01 - 08.01.02, split course. Conditions of exposure: sector 80-180time 179, sector 330-210time 173 C. Single focal dose of 4 Gy was delivered with a daily crushing, Gr 22 times a day with an interval of 4-5 hours. Total focal dose was 56 Gy (64 Gy in WDF).

Upon completion of the radiation therapy pain completely stopped, no appetite, moderate nausea, diarrhea up to 2 times per day, leukopenia, grade II does not require medical treatment.

General analysis of blood from 08.01.2002,: hemoglobin 102 g/l, erythrocytes-3,71012colour index is 0.8, leukocytes 2,8109, leukocyte formula: stab - 7%, segmented - 56%, eosinophils 2%, and lymphocytes 27%, monocytes - 8%.

Biochemical analysis of blood from 08.01.2002: glucose 5.0 mon 113,8 mmol/l, amylase 7,6 ED, alanine aminotransferase 0.4 mmol/l, alkaline phosphatase 41,2 ED, thymol test 1.4 UNITS.

The patient was discharged from further attendance for holding autohemotherapy.

live on 23.02.2002, the turnout for control tests. Patient no complaints. The condition is satisfactory. Weight gain of 5 kg

Objective: the language clean, damp, the abdomen is soft, painless, extensive education in the epigastric region is not defined. Chair, diuresis normal. The Karnofsky Index 70-80%.

24.02.2002 - 21.03.2002, in the outpatient setting, the course of autohemotherapy. Total dose injected chemotherapy: 5-fluorouracil 4000 mg, doxorubicin 100 mg, mitomycin C 12 mg. Observed adverse reactions in the form of loss of appetite, nausea, vomiting, first degree on the first day of autohemotherapy, leukopenia, grade II do not require medical correction and intractable yourself after autohemotherapy.

In General, the analysis of blood from 22.03.2002,: hemoglobin 102 g/l, erythrocytes-3,71012colour index is 0.8, leukocytes 3,5109, leukocyte formula: band - 15%, segmented - 64%, eosinophils - 1%, lymphocytes -12%, monocytes - 8%.

Biokhimicheski/l, associated is not defined, creatinine 102,1 mmol/l, amylase 6.7 UNITS, alanine aminotransferase 0.4 mmol/l, alkaline phosphatase 41,2 ED, thymol test 1,2 UNITS.

3.04.2002, performed ultrasound examination of abdominal cavity organs (Fig.2). On the sonogram pancreas deformed in the area of the head is enlarged. Swelling of the head hypoechoic size of 3.28to 3.89. The blood supply to tumors of the peripheral avascular. The intensity of blood flow hypovascular in the peripheral zones.

The patient is kept under observation for 3 months without evidence of disease progression, active, maintains itself, pain is absent. The Karnofsky Index 70-80%.

Technical and economic efficiency "method of treatment of irresectable pancreatic cancer" is that the combined effect of remote gamma-therapy and autohemotherapy contributes to:

- full and partial resorption of the tumor,

- the reduction or disappearance of pain,

- improvement of the General condition of patients and the status of metabolic processes,

- reduce the number and severity of radiation reaction,

- reduce the toxicity of chemotherapy,Claims

A method for the treatment of irresectable pancreatic cancer, including remote gamma-therapy, chemotherapy, characterized in that the remote gamma-therapy on the pancreas of conduct in the individual mode, depending on the size of the tumor: tumor size - dual-axis or single-axis two-sector rotation, and when the size of the tumor more than 10 cm in static multi-field mode; single focal dose of 4 Gy down fractionally, 2 G, 2 times a day with an interval of 4-5 hours, up to a total focal dose 24-28 G; course resume after a two-week break before summing the total focal dose 52-56 Gr; 2-3 weeks are autohemotherapy: perform blood withdrawal in the amount of 240 ml 80 ml 3 vials with standard preservative, the first day of the first vial Autocraft injected with 5-fluorouracil based 600 mg/m2the second bottle is the solution of doxorubicin at a dose of 30 mg/m2the third bottle is a solution of mitomycin C in the dose of 10 mg/m2the vials are incubated at 37 C for 45 min, after which produce reinfuse blood with cytostatics in the order mentioned, on the 8th day Sabirov with cytostatic for 45 min at 37 With and administered to the patient; on the 27th day collect 160 ml of blood of the patient in 2 bottles with standard preservative 80 ml in each vial, the first vial is administered 5-fluorouracil 600 mg/m2the second bottle is the solution of doxorubicin at the rate of 30 mg/m2the vials are incubated at 37 C for 45 min, and blood with dissolved chemicals is re-infused in the order mentioned, on the 36th day collect the patient's blood in the amount of 80 ml in a bottle with a standard preservative in the vial Autocraft administered 5-fluorouracil at a dose of 600 mg/m2, incubated for 45 min at 37 With and administered to the patient; this course doses of chemotherapy are: mitomycin C 10 mg/m2, doxorubicin 60 mg/m25-fluorouracil - 2400 mg/m2.

 

Same patents:

The invention relates to medicine, namely to dermatology, and relates to a method of treatment of mycosis fungoides
The invention relates to medicine and can be used for head and neck tumors, biliodigestive zone, rectum

The invention relates to palletization derived bacteriochlorophyll formula I, I' or I"

where a is a HE, OR1, -O-(CH2)n-Y, -S-(CH2)n-Y, -NH-(CH2)n-Y, -O-(CH2)2-OH, -NH-(CH2)2-NH-BOC, or-N(CH2-CH=CH2)2where R1represents Na+, K+, (CA2+)0,5, (Mg2+)0,5Li+, NH+4,+NH3-C(CH2OH)3,+NH3-CH2-(CHOH)4-CH2OH,+NH2(CH3)-CH2(SNON)4-CH2OH, or+N(Cn'H2n'+1)4; R2represents N or C1-C12the alkyl for the compounds of formula I', and R2represents H, HE or COOR4for the compounds of formula I, where R4represents C1-C12alkyl or C3-C12cycloalkyl; R3represents N or C1-C12the alkyl for the compounds of formula I', and R3represents H, HE, or C1-C12alkyl or alkoxy with the R'3X-where R'1, R'2and R'3each independently represents-CH3or-C2H5; X represents F, Cl, Br or I, n is 1, 2, 3 or 4, and where * denotes an asymmetric carbon atom and --- represents a single saturated bond or an unsaturated double bond pharmaceutical composition having a capacity of detection or treatment of tumors containing at least one compound of formula I, I' or I", three methods for obtaining the compounds of formula I

The invention relates to derived-alanine General formula I:

in which Q1or Q3independently from each other represent CH or N, they cannot mean N; R1represents H, A, Ar or Hal, R2denotes H or A,

each of R4and R5independently denotes H, a or Hal, R6represents H or a, a denotes alkyl with 1-6 carbon atoms, Ar is an unsubstituted aryl, Hal denotes F, Cl, Br or I, n is 2, 3, 4, 5 or 6, m is 1, 2, 3 or 4, as well as their physiologically acceptable salt and solvate; two methods for their preparation and pharmaceutical product having the properties of integrins inhibitor

The invention relates to medicine, to methods of combination therapy for cancer patients

The invention relates to medicine, namely to breast care, gynecology, endocrinology

The invention relates to biology and medicine
The invention relates to medicine, specifically to Oncology, and can be used in clinical practice Oncology hospitals

The invention relates to medicine, to methods of combination therapy for cancer patients
The invention relates to methods of treatment of oncological diseases, namely locally advanced and invasive carcinoma of the cervix

The invention relates to medical equipment, namely to devices used in radiosurgery
The invention relates to medicine, namely to Oncology, and can be used in the treatment of vulvar cancer

The invention relates to medicine, namely to the field of radiation therapy, and is intended for planning neutron capture therapy
The invention relates to medicine, namely to Oncology, and can be used for the treatment of malignant tumors of the nasopharynx

The invention relates to methods of radiation therapy irradiation elementary particles, namely when performing rotational radiation therapy of malignant tumors
The invention relates to medicine, in particular to the venereal diseases, urology and gynecology
Up!