MXPA05004514A - Anti-tumor combinations comprising proteins and chemotherapeutics. - Google Patents

Abstract

a. goat liver perchloric extract containing the protein UK 114, b. cyclophosphamide; c. doxorubicin or other anthracyclins; d. 5-fluorouracil, in the form of combination for the simultaneous, separated or sequential use in chemotherapy.

Description

ANTITUMORAL COMBINATIONS COMPRISING PROTEINS AND ANTINEOPLASTICS Description of the Invention The present invention relates to compositions that contain: a. perchloric extracts of goat liver containing protein UK114; b. cyclophosphamide; c. doxorubicin or other anthracyclines; d. 5 - f iuorcuracil in the form of combination for sequential, separate or simultaneous use in chemotherapy. The invention relates to the use of the UK 114 protein or goat liver perchloric extracts containing them for the preparation of a medicament for the synergistic treatment of cancer in combination with standard chemotherapy protocols. Currently available cancer treatment with antimalarials usually requires. standard protocols in which a greater number of drugs are combined according to the pre-established dosage schemes, and developed in order to optimize therapeutic responses, while decreasing the onset of resistance and • toxicity or side effects.

Some of these treatment protocols have been established for many years and are part of the knowledge of those experts in oncology. One of the most widely used protocols, particularly in the first-line treatment of breast carcinomas, is known as FAC because of the initials of the three drugs that make up the antineoplastic "cocktail": fluorouracil, adriamycin® (doxorubicin), and cyclophosphamide . The protocol comprises in particular treatment cycles of four to six weeks every four weeks, for a total duration of four six months: the dosage scheme consists of the administration of 500 mg / m2 of Fluorouracil, 50 mg / m of doxorubicin and 500 mg / m2 of cyclophosphamide on day 1, followed by the administration of 500 mg / m2 of fluorouracil on days 5-8, even though this is the protocol of choice in the first-line treatment of carcinomas of breast and has achieved satisfactory results in terms of percentage is "partial or complete response, there is still a need to improve the effectiveness and / or the therapeutic index of currently available antitumor drugs." Proteins with activity were described in O 92 / 10197, WO 96/02567 and WO97 / 30154: one of these proteins, isolated from goat liver extract, consists of an amino acid sequence of 137 amino acids reported in Biochim.Biophys.Acta, 1 442 (1998) 49-59, in which the expression of the corresponding cDNA sequence in Escherichia coli is also described. Both the protein and the perchloric extract of goat liver contain this protein, described in WO92 / 10197, are in the present under study as potential drugs for a variety of therapeutic applications, particularly for the treatment of cancer of various origins, against which have shown marked cytotoxic activity, apparently mediated by antibodies, as reported for example in British J. cancer, 79 (1), 1999, 54-58; J. Tumor Marker Oncol. 12 (1), 1997, 29-37; Virchws Arch (1997), 431: 323-328; Int. J. Oncol. 10: 779-735, 1997; ibidem 8: 543-548, 1996. It has been found that the protein known as UK 114 or the extract containing the protein UK 101, administered simultaneously, previously or sequentially to the drugs usually used in chemotherapy protocols, are able to improve remarkably its activity, while its side effects decrease. In accordance with the present invention, the UK114 and / or UK101 proteins are preferred in combination with the FAC treatment scheme mentioned above, in particular for the treatment of breast carcinomas. The FAC protocol will of course be adapted to each particular case, according to the doctor's judgment, while the -UK114 / UK101 proteins will be administered parenterally, preferably subcutaneously, in doses of 1 to 20 mg, preferably from 2 to 10 mg, once or twice a week through the duration of the chemotherapy cycles. The administration of the UK 114/101 proteins can be further carried out during the weeks of the FAC treatment and during the time between two subsequent cycles of the FAC treatment. The beneficial effects of UK114 / 101, synergistic type or any other advantageous type, can also be observed in combination with other anti-cancer drugs, alone or in appropriate combinations, although the use in combination with fluorouracil, doxorubicin (or other anthracyclines such as idarubicin , epirubicin) and cyclophosphamide according to the described protocol is preferred. For an intended therapeutic use, the UK114 protein obtained by extraction or by recombinant DNA techniques described in Biochim. Biophys. Minutes, 144.2 (1998) 49-59 and WO 00/63368, or the perchloric extract of goat liver described in WO 92/10197, may also be used. Preliminary tests on a restricted group of 22 patients with ductal carcinoma or medullarly infiltrated breast carcinomas, from an age range of 27 to 76 years, under the FAC protocol (500 mg / m2 fluorouracil, 50 mg / m2 doxorubicin and 500 mg / m2 of cyclophosphamide on day • 1, followed by an administration of 500 mg / m2 of fluorouracil on day 8, every four weeks for four months) have proved that the single treatment with 10 mg of protein UK101 every week by four months improves the quality of life, reduces the analgesic consumption and increases the therapeutic responses expected from the FAC treatment alone. It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention is that which is clear from the present description of the invention.

Claims (4)

1. Claims Having described the invention as above, the content of the following claims is claimed as property: i. - Pharmaceutical composition characterized because it contains: to. perchloric extracts of goat liver containing, the protein UK 114; b. cyclophosphamide; c. doxorubicin or other anthracyclines; d. 5- fluorouracil; in the form of combination for sequential, separate or simultaneous use in chemotherapy.
2. 2. - Use of the protein UK114 or perchloric extracts of goat liver containing the same for the manufacture of a drug for the synergistic treatment of cancer in combination with standard chemotherapy protocols.
3. 3. Use according to claim 2 in combination with 5-fluorouracil, cyclophosphamide and doxorubicin.
4. 4. - Use according to claims 2 or 3 for the treatment of breast carcinomas.