Method for the treatment of primary liver cancer and kit for treatment of primary liver cancer

 

(57) Abstract:

The invention relates to medicine, in particular to Oncology. Method for the treatment of primary liver cancer includes the introduction into the hepatic artery in the beginning of alpha-fetoprotein in saline solution, and then antitumor substances previously dissolved in 96% ethyl alcohol, to which is optionally added substance, ultrablue, as an antitumor substance use doxorubicin at a dose of 30-40 mg dissolved in 1 ml of 96% ethyl alcohol, 10 ml of the substance of Ultrasuede, alpha-fetoprotein is administered at a dose of 2 mg in 10 ml saline. Set for treatment of primary liver cancer contains antitumor substance, 96% ethanol, the substance ultrablue, alpha-fetoprotein, a sterile saline solution volume of 15 ml vials, which as antitumor substance containing doxorubicin in the amount of 30-40 mg 3-4 vials of 10 ml, sterile substance, ultrablue 2 ampoules of 5 ml, sterile liofilizovannye the preparation of alpha-fetoprotein person in the amount of 2 mg vials with 10 ml of 96% ethanol in a volume of 1 ml vials. The proposed method is more efficient than known in the field, and less than TT to find application in chemotherapy of cancer patients, suffering from various forms of cancer, such as primary and metastatic liver cancer, breast cancer, leukemia and other

Primary and metastatic liver cancer according to the statistical data is often the cause of death of patients, firstly, because of the difficulty to timely diagnose the disease and to conduct surgical removal of the tumor and, secondly, because of the inability to conduct an effective conservative chemotherapy because of the risk of irreversible toxic liver damage and kidney damage (cirrhosis, massive thrombosis, renal and liver failure, etc.,) in the treatment of anticancer antibiotics. In addition, primary liver cancer is among resistant to chemotherapy diseases. The effectiveness of systemic chemotherapy with fluorouracil is extremely low, some improvement of the treatment results was observed with systemic chemotherapy with doxorubicin. However, at the same time observed a large number of cases total toxic reactions, often incompatible with life.

Know the use of regional chemotherapy, in which doxorubicin was injected into the tumor lesion by means of a catheter through the hepatic artery, which allowed to increase appease vessels of the liver using lipiodol of ULTRAGLIDE helped to limit the spread of doxorubicin while simultaneously angiostatic effects of the drug, to restrict the blood supply to the tumor and to supressive its growth. However, high dose of the drug was left non-specific toxicity at a sufficiently high level (40%) did not significantly increase the average life of patients. If inoperable form of primary and metastatic liver cancer, the average life of patients after diagnosis did not exceed 2-5 months, with regional therapy using doxorubicin and lipiodol of ULTRAGLIDE life expectancy has increased to 9-12 months (see, for example T. Konno et al in Eur. J. Cancer, 1992, N 28, p.403-408).

In this article it is proposed to use for regional introduction to the area of the tumor anti-cancer drugs hydrophobic compound lipiodol of ULTRAGLIDE representing the oil from poppy seed substituted with ethyl ether, the ether of glycerol with the addition of 0.38% iodine. With the introduction of suspension lipiodol of ULTRAGLIDE is a blockage of the small blood vessels feeding the tumor. The local area embolism does not dissolve up to 2 weeks. While introduction to this area of anticancer drug doxorubicin is to limit the scope of active influence of prepa sharply reduced its toxic side effects while increasing the effectiveness of treatment.

It is also known that uncomprehending marker alfafetoprotein (AFP) able to selectively absorbed cancer but not normal cells and has the ability to bind different antibiotics and purposefully to transport them in cancer but not in normal cells (see, for example, Deutsch H. F. in J. Tumor Marker Oncology, 1994, No. 9, p.1-14).

In addition, recently installed the ability of the AFP to cause the software to the death or apoptosis in cancer but not normal cells, and modulate the apoptotic signals induced by other factors, made it possible to offer a comprehensive anti-cancer drugs based on ACE for cured cancer treatment (Dudich, E. I. et al - Tumor Biol., 1998, 19, 30-40).

Closest to the claimed is a method of treatment of primary liver cancer, comprising introducing into the hepatic artery in the beginning of alpha-fetoprotein in physiological solution, and then antitumor substances previously dissolved in 96% ethyl alcohol, to which is optionally added substance, ultrablue (see, for example, patent RU N 2065307, MKI A 61 K 38/17, 1994).

The disadvantage of this method is the complexity of the manufacture of an antitumor substance doxorubicin - astroknot to a minimum.

The proposed method can reduce therapeutic dose of the drugs and reduce the likelihood of adverse toxic effects, while increasing anti-cancer therapeutic effect.

This object is achieved in that in the proposed method of treatment for primary liver cancer, comprising introducing into the hepatic artery in the beginning of alpha-fetoprotein in saline solution, and then antitumor substances previously dissolved in 96% ethyl alcohol, to which is optionally added substance, ultrablue, as an antitumor substance use doxorubicin at a dose of 30-40 mg dissolved in 1 ml of 96% ethyl alcohol, 10 ml of the substance of Ultrasuede, alpha-fetoprotein is administered at a dose of 2 mg 10 ml of saline.

The positive effect of the proposed method of treatment using doxorubicin and AFP is achieved by reducing the concentration of free antibiotic in the tissues and the increase in the proportion of antibiotic associated with AFP, carrying out targeted transfer of a cytotoxic agent in cancer cells, bypassing healthy. This proposal used the ability of the AFP and directed specifically to enhance cytotoxics the temporal significantly reduce non-specific toxicity of anticancer antibiotics against normal tissues significantly reduce therapeutic dose and to reduce the likelihood of adverse toxic effects. In addition, the inventive method of treatment can be used in patients with contraindications to the use of steroid hormones, whereas in the known method - prototype - use complex doxorubicin - estrone is possible only for a certain category of patients with hormone-independent tumors.

Implementation of the proposed method is as follows:

in the treatment of cancer with the help of the proposed comprehensive chemotherapy drugs doxorubicin and AFP use a mixture of 30-40 mg of doxorubicin and 2 mg of purified AFP person obtained from umbilical cord serum. The drug is administered intravenously or regionalno in the area of the tumor using the method of transcatheter regional chemotherapy using lipiodol of Ultrasuede. Use of the method of regional chemotherapy using the proposed method is more preferably in the presence of primary or metastatic tumors in the liver. If determenirovana dissemination of the tumor on the body shows a systemic intravenous proposed is 96% ethyl alcohol, then add 10 ml of sterile drug lipiodol of Ultrasuede and vigorously shaken to the formation of fine suspension. AFP - 2 mg sterile dissolved in 10 ml of isotonic saline and drip injected through the catheter in the area of the tumor via the hepatic artery, then enter solution of doxorubicin in lipiodol ULTRAGLIDE.

Treatment is again carried out after 4-5 weeks in the presence of positive dynamics.

Systemic chemotherapy 30-40 mg of doxorubicin dissolved in 1 ml of 96% ethyl alcohol, then add 10 ml of sterile isotonic saline solution and mixed with a sterile solution AFP (2 mg in 100 ml saline). Then the drug is administered intravenously through a drip within 2-3 hours as AFP may also use AFP person obtained from the culture medium AFP - secreting cultured in vitro cell lines human hepatoma, for example, HepG2 or recombinant AFP person, expressed in bacterial cells Escherichia Coli.

Only the proposed method were treated 6 patients aged from 15 to 64 years. The pre-selection of patients served Otsu and efficiency were carried out according to who criteria. Were studied the following parameters after treatment: duration of remission, time from start of treatment until disease progression during the treatment: "stabilization", "minimum", "partial", "full effect", as well as the life expectancy of patients, which was calculated from the start of treatment. During treatment, patients were assigned to the following types of tests: coagulation tests, ECG, clinical blood and urine tests, laparoscopy, the determination in blood alpha-fetoprotein, angiography, computed tomography, ultrasound tomography.

The main results of the study are presented in the table.

Example 1. Excerpt from the history from 102.12.96. Patient M,, male, age 64 years.

Based on the data and ultrasonic tomographic studies and x-ray contrast angiography was diagnosed adenocarcinoid liver. Due to the large tumor size (diameter about 7 cm) surgical removal is not recommended. The patient was made 3 consecutive injections of the drug AFP - doxorubicin - substance. Directed by means of a catheter through the hepatic artery has imposed a suspension of the solution of 2 mg of AFP in 5 ml of saline solution and 35 ml of doxorubicin, suspended in 1 the e liver of the patient, made 4 weeks after the first injection, showed a significant decrease in tumor size (>50%). Subsequent injections resulted in the stabilization process, and observation of the patient within one year after the start of therapy showed a significant improvement in his condition and the absence of any manifestations nonspecific toxicity, typical chemotherapy doxorubicin.

Example 2. Excerpt from the history from 126.10.96. Patient A. J., female, the age of 54 years. Diagnosis: metastatic liver lesion after surgical removal of breast cancer (right). One year after surgery to remove breast cancer and excision of axillary lymph nodes in patients with tomographic examination found multiple metastatic tumors in the liver with a diameter of 1 see the Patient were made two injections of the drug AFP - doxorubicin - substance, ultrablue. Directed by means of a catheter through the hepatic artery has introduced a suspension solution of 2 mg of AFP in 5 ml of saline solution and 40 ml of doxorubicin, suspended in 10 ml of lipiodol of Ultrasuede. 4 weeks after the first injection was made tomographic and angiographic diagnostic study pécs is rozvedena the re-injection of the drug. During the observation period (8 months), the patient was not discovered a new tumor formation in the liver. The process of remission was not complicated by toxic reaction to chemotherapy doxorubicin.

Example 3. Excerpt from the history from 112.05.96. Patient A. D., male, age 19 years. Diagnosis: disseminated rhabdosarcoma intestine with multiple metastases in the pelvic organs and peritoneum. Triple produced surgical excision of the tumor process areas of the intestine. Rapid progression of neoplastic processes. Patients received intravenous drug AFP (3 mg in 100 ml saline) and then entered the drug doxorubicin (40 mg in 100 saline) drip for 3 hours monitor patients within one week after injection showed a significant improvement in General condition and tone with virtually no toxic manifestations, typical in the treatment of doxorubicin. Upon further observation of patients noted a stabilization process and no further progression of tumor growth. The re-injection of the drug according to the same scheme was made in 3 weeks. The patient was observed within 3 months after the start of therapy AF-doxorubin is no set treatment for patients with primary liver cancer.

The prototype is set for the treatment of primary liver cancer (see, for example, patent RU N 2065307, MKI A 61 K 38/17, 1994).

This set includes sterile liofilizovannye drug AFP person in the amount of 1-10 mg in vials with a capacity of 10 ml, sterile drug doxorubicin-estrone in the amount of 20-60 mg in vials with a capacity of 15 ml, sterile saline solution volume of 15 ml vials, ethyl alcohol by volume of 5 ml vials, sterile substance, ultrablue volume of 20 ml in two ampoules of 10ml

The proposed set for the treatment of primary liver cancer includes drugs doxorubicin in the amount of 30-40 mg, 3-4 vials of 10 ml, sterile substance, ultrablue in two ampoules of 5 ml and sterile liofilizovannye drug AFP person in the amount of 2 mg per dose to 10-ml vials. In addition, the kit includes vials with sterile saline solution (15 ml of 0.9% sodium chloride in distilled pyrogen-free water) and with 96% ethanol (1 ml). The set is implemented as follows: in regional chemotherapy 30-40 mg of doxorubicin dissolved in 1 ml of 96% ethyl alcohol, then add 10 ml of sterile drug substance, ultrablue and vigorously shaken to education melodiler in the area of the tumor via the hepatic artery, then enter solution of doxorubicin in lipiodol, prepared as described above. Treatment is again carried out after 4-5 weeks with positive dynamics.

Systemic chemotherapy 30-40 mg of doxorubicin dissolved in 1 ml of 96% ethyl alcohol, then add 10 ml of sterile isotonic saline solution and mixed with a sterile solution AFP (2 mg in 100 ml saline). The drug is administered intravenously through a drip in 2-3 hours

1. Method for the treatment of primary liver cancer, comprising introducing into the hepatic artery in the beginning of alpha-fetoprotein in saline solution, and then antitumor substances previously dissolved in 96% ethyl alcohol, to which is optionally added substance, ultrablue, characterized in that as an antitumor substance use doxorubicin at a dose of 30-40 mg dissolved in 1 ml of 96% ethyl alcohol, 10 ml of the substance of Ultrasuede, alpha-fetoprotein is administered at a dose of 2 mg in 10 ml saline.

2. Set for treatment of primary liver cancer containing antitumor substance, 96% ethyl alcohol, substance, ultrablue, alpha-fetoprotein, a sterile saline solution volume of 15 ml vials, the vials of 10 ml, sterile substance, ultrablue 2 ampoules of 5 ml, sterile liofilizovannye the preparation of alpha-fetoprotein person in the amount of 2 mg vials with 10 ml of 96% ethanol in a volume of 1 ml vials.

 

Same patents:

The invention relates to pharmaceutical industry and the receipt of liofilizirovannogo preparation of alpha-fetoprotein (AFP), belonging to the group of immunomodulators and used as a treatment for cancer

The invention relates to the field of medicine and are expected to be used in the treatment of malignant tumors
The invention relates to the food industry

The invention relates to medicine, specifically to pharmacology, and relates to the use of previously known antimicrobial colloidal preparations of silver of the protargol and colloid for a new purpose as antihypoxants

Eye film // 2076672
The invention relates to medicine, in particular to ophthalmology, and can be used in the treatment of traumatic injuries, trophic disorders and chemical burns of the cornea, conjunctiva

2-globulin cystic fluid associated with the true disease" target="_blank">

The invention relates to medicine, in particular dermatology, namely the method of obtaining2globulin cystic fluid associated with the true disease
The invention relates to medicine, namely neurosurgery, neurology and psychotria and can be used for examination of patients with suspected epilepsy
The invention relates to medicine and can be used in the treatment of diseases of the Central nervous system

The invention relates to medicine, in particular for cell therapy and can be used for the treatment of diseases caused by disorders of the immune system, for example, diabetes

The invention relates to medicine, traumatology

The invention relates to medicine, namely to Oncology, clinical immunology, and can be advantageously used for the treatment of cancer
The invention relates to the production of biogenic drugs and is an extract from the placenta of cows with bacteriophages, have an antimicrobial effect on the microflora of the uterus without irritation mucous membrane, designed for the treatment and prevention of postpartum diseases of female farm animal
The invention relates to medicine, in particular to pharmaceutical compositions based on natural product, normalizes metabolic processes

The invention relates to medicine, in particular to compositions having therapeutic purpose by external application

The invention relates to pharmaceutical industry
Up!