Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2001-03-21
2002-08-27
Owens, Amelia (Department: 1625)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S184000, C514S316000, C514S410000, C514S459000
Reexamination Certificate
active
06441026
ABSTRACT:
The present invention relates to combinations of taxol, Taxotere and their analogues and substances which are therapeutically useful in the treatment of neoplastic diseases.
Taxol, Taxotere and their analogues, which possess noteworthy antitumor and antileukemic properties, are especially useful in the treatment of cancers of the colon, ovary, breast or lung.
The preparation of taxol, Taxotere and their derivatives form the subject, for example, of European Patents EP 0,253,738 and EP 0,253,739 and International Application PCT WO 92/09,589.
Generally, the doses used, which depend on factors distinctive to the subject to be treated, are between 1 and 10 mg/kg administered intraperitoneally or between 1 and 3 mg/kg administered intravenously.
It has now been found, and this forms the subject of the present invention, that the efficacy of taxol, Taxotere and their analogues may be considerably improved when they are administered in combination with at least one substance which is therapeutically useful in anticancer treatments and has a mechanism identical to or different from this of taxane derivatives.
Among substances which may be used in association or in combination with taxol, Taxotere or their analogues, there may be mentioned alkylating agents such as cyclophosphamide, isosfamide, melphalan, hexametyl-melamine, thiotepa or dacarbazine, antimetabolites such as pyrimidine analogues, for instance 5-fluarouracil and cytarabine, or its analogues such as 2-flourodeoxycytidine, or folic acid analogues such as methotrexate, idatrexate or trimetrexate, spindle poisons including vinca alkaloids such as vinblastine or vincristine or their synthetic analogues such as navelbine, or estramustine or taxoids, epidophylloptoxins such as etoposide or teniposide, antibiotics such as daunorubicine, doxorubicin, bleomycin or mitomycin, enzymes such as L-asparaginase, topoisomerase inhibitors such as camptothecin derivatives chosen from CPT-11 and topotecan or pyridobenzoindole derivatives, and various agents such as procarbazine, mitoxantrone, platinum coordination complexes such as cisplatin or carboplatin, and biological response modifiers or growth factor inhibitors such as interferons or interleukins.
Moreover, since the activity of the products depends on the doses used, it is possible to use higher doses and to increase the activity while decreasing the toxicity phenomena or delaying their onset by combining growth factors of the haematopoietic type such as G-CSF or GM-CSF or certain interleukins with taxol, Taxotere, their analogues or their combinations with other therapeutically active substances.
The combinations or associations according to the invention enable the phenomena of pleiotropic resistance or “multi-drug resistance” to be avoided to delayed.
More especially, the invention relates to combinations of taxol, Taxotere and their analogues with vinca alkaloids, cyclophosphamide, 5-fluorouracil, doxorubicin, cisplatin, navelbine, camptothecin, and etoposide.
The improved efficacy of a combination according to the invention may be demonstrated by determination of the therapeutic synergy. A combination manifests therapeutic synergy if it is therapeutically superior to one or other of the constituents used at its optimum dose (T. H. Corbett et al.,
Cancer Treatment Reports,
66:1187 (1982)).
To demonstrate the efficacy of a combination, it may be necessary to compare the maximum tolerated dose of the combination with the maximum tolerated dose of each of the separate constituents in the study in question. This efficacy may be quantified, for example, by the log
10
cells killed, which is determined according to the following formula:
log
10
cells killed=
T−C
(days)/3.32×
T
d
in which T−C represents the time taken for the cells to grow, which is the mean time in days for the tumors of the treated group (T) and the tumors of the treated group (C) to have reached a predetermined value (1 g for example), and T
d
represents the time in days needed for the volume of the tumor to double in the control animals [T. H. Corbett et al.,
Cancer,
40, 2660-2680 (1977); F. M. Schabel et al., Cancer Drug Development, Part B,
Methods in Cancer Research,
17, 3-51, New York, Academic Press Inc. (1979)]. A product is considered to be active if log
10
cells killed is greater than or equal to 0.7. A product is considered to be very active if log
10
cells killed is greater than 2.8.
The combination, used at its own maximum tolerated dose, in which each of the constituents will be present at a dose generally not exceeding its maximum tolerated dose, will manifest therapeutic synergy when the log
10
cells killed is greater than the value of the log
10
cells killed of the best constituent when it is administered alone.
REFERENCES:
patent: 4857653 (1989-08-01), Colin et al.
patent: 4876399 (1989-10-01), Holton et al.
patent: 5015744 (1991-05-01), Holton
patent: 5136060 (1992-08-01), Holton
patent: 5229526 (1993-07-01), Holton
patent: 5262409 (1993-11-01), Margolis et al.
patent: 5294737 (1994-03-01), Ojima
patent: 5466834 (1995-11-01), Holton
patent: 5494683 (1996-02-01), Liversidge et al.
patent: 5645988 (1997-07-01), Vande Woude et al.
patent: 5728687 (1998-03-01), Bissery
patent: WO 92/19765 (1992-11-01), None
Rowinsky et al., Sequences of Taxol and Cisplatin: A Phase I and Pharmacologic Study,J. of Clin. Oncology,9(9):1692-1703 (1991).
Rowinsky et al., The Clinical Pharmacology and Use of Antimicrotubule Agents in Cancer Chemotherapeutics,Pharmac. Ther.,52:35-84 (1991).
Bissery et al., Abstract 2645,Proceedings of the AACR,33:443 (Mar. 1992).
Bissery et al., “Preclinical Pro file of Docetaxel (Taxotere): Efficacy as a Single Agent and in Combination,”Seminars in Oncology,22(6)(Suppl 13):3-16 (1995).
Bissery et al., “The Taxoids,”Cancer Therapeutics: Experimetnal and Clinical Agents,pp. 175-193 (1995).
Bissery et al., Abstract 1599, “Preclinical In Vivo Activ ity of Docetaxel Containing Combinations,”Proceedings of the ASCO,14:489 (1995).
Bissery et al., Abstract 50, “Preclinical In Vivo Ev aluation of Docetaxel (Taxotere®) Containing Combinations,”Proc. of the Cytoskeleton and Cancer,p. 50 (Sep. 17-20, 1995).
Mirabelli et al., “A Murine Model to Evaluate the Ability of In Vitro Clonogenic Assays to Predict the Response to Tumors In Vivo,”Cancer Res.48:5447-5454 (1988).
Llombart-Cussac et al., Proceedings of ASCO, 16 (1997) Abstract No. 629.
Aventis Pharma S.A.
Owens Amelia
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