Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2002-01-23
2003-04-15
Reamer, James H. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
Reexamination Certificate
active
06548531
ABSTRACT:
FIELD OF THE INVENTION
The present invention is directed to a method of cancer therapy by administering (i) a pharmaceutical composition containing a compound of formula
and (ii) a pharmaceutical composition containing paclitaxel (commercially available as Taxol™). The invention is also directed to a kit containing both of the above compositions.
BACKGROUND OF THE INVENTION
The compounds of formula I below are known to be cell cycle inhibitors having potent anticancer therapeutic activity, in particular in solid tumors such as breast and colon cancers. See, e.g. U.S. Pat. Nos. 5,057,614 and 6,048,887.
Paclitaxel is also known to be useful in cancer therapeutics. See, e.g., U.S. Pat. Nos. 5,641,803 and 5,670,537 (and the references cited therein).
It has now been discovered that compounds of formula I are especially effective in cancer therapy when administered in combination with paclitaxel.
SUMMARY OF THE INVENTION
The present invention relates to a method of treating a patient suffering with cancer comprising administering to the patient, either concomitantly or sequentially, a first component consisting of a pharmaceutical composition containing as an active ingredient a compound of formula I or a pharmaceutically acceptable salt or ester of said compound and a second component consisting of a pharmaceutical composition containing paclitaxel, the amount of each component being such that the combination of components is therapeutically effective.
This combination of chemotherapeutic compounds is particularly useful in the treatment of breast, colon, rectal, lung, uterine and prostate cancers.
It was unexpectedly found that administration of the two components in accordance with the present invention results in improved antineoplastic effects that are significantly superior to the results obtained with each compound alone. Namely, administration of the two components in accordance with the present invention resulted in an improved therapeutic index (that is, superior efficacy) in comparison to either component alone without a significant increase in toxicity. Alternatively the invention permits reduction of the amount of at least one component (in comparison the amount typically given in monotherapy) while retaining a desirable therapeutic index. In preferred embodiments, the amount of both components (in comparison the amount typically given in monotherapy) is reduced affording reduced toxicity while still retaining a desirable therapeutic index.
The above findings were unexpected inasmuch as similarly designed in vitro studies using compounds of formula I in combination with other antineoplastic agents (such as gemcitabine, 5-FU and carboplatin) did not produce the magnitude of effect observed with compounds of formula I in combination with paclitaxel.
In another aspect, the invention relates to a kit. The kit comprises a first component and a second component. The first component contains one or more oral unit dosage forms of an active ingredient selected from a compound of formula I or a pharmaceutically acceptable salt or ester of said compound. The second component contains one or more injectable unit dosage forms of paclitaxel.
REFERENCES:
patent: 5057614 (1991-10-01), Davis et al.
patent: 5641803 (1997-06-01), Carretta et al.
patent: 5670537 (1997-09-01), Canetta et al.
patent: 6048887 (2000-04-01), Dhingra et al.
patent: 6080777 (2000-06-01), Schiff
patent: 6277844 (2001-08-01), Spector et al.
patent: 6335194 (2002-01-01), Bennett et al.
patent: 6350786 (2002-02-01), Albano et al.
patent: 2002/0052409 (2002-05-01), Ghosh
Trivedi C. Redman B. Flaherty L. E. Kucuko Du W. Heibrun L. K. Hussain M. Weekly 1-hour Infusion of Paclitaxel. Clinical Feasibility and Efficacy in Patients with Hormone-refractory Prostate Carcinoma. Cancer vol. 89(2): pp. 431-436, 2000.
2000 (PDR) Physicians' Desk Reference, Medical Economics Co., 2000 (PDR® entry for Taxol injection (Bristol-Myers Squibb Oncology/Immunology) pp. 881-887.
Paclitaxel in Advanced Non-Small Cell Lung Cancer: An Alternative High-Dose Weekly Schedule. A Kerley, Wallace III MD, Chest. vol. 117(4) Suppl. 1, 4/00 152S-155S.
Preclinical Characterization of Ro 31-7453, A New Cell Cycle Inhibitor S. Ritland et al. Proceedings of the European Spring Oncology Conference, Apr. 2000.
Phase 1 Clinical & Pharmacokinetic Study of the Novel Cell Cycle Inhibitor Ro 31-7453, Cassidy et al. Proceedings of the American Society for Clinical Oncology, May, 2000.
Evaluation of Effects of Dose and Schedule on Efficacy and Toxicity of Orally Administered Ro 31-7453 in Tumor Bearing Nude Mice, Dhingra, U. et al.,Proceedings of the American Association for Cancer Research Annual Meeting, Apr. 1-5, 2000.
The Effect of Ro 31-7453 on the Growth of MTLn3 Rat Mammary Adenocarcinoma Cells at Primary and Metastatic Sites, Goggin, B.S., et al.,Proceedings of the American Association for Cancer Research Annual Meeting, Apr. 1-5, 2000.
Comparison of Effect of First and Second Course of Treatment of Orally Administered Ro 31-7453 on Efficacy and Toxicity in Two Human Xenograft Models in Nude Mice, Dhingra, U. et al.,Proceedings of the American Association for Cancer Research Annual Meeting, Apr. 1-5, 2000.
Ro 31-7453 Inhibits VEGF-and bFGF-Induced Corneal Angiogenesis in the Mouse, Nevins, T. D., et al.,Proceedings of the American Association for Cancer Research Annual Meeting, Apr. 1-5, 2000.
Identification and Preclinical Characterization of Metabolites of Ro 31-7453, A New Cell-Cycle Inhibitor, Dhingra, U. et al.,Proceedings of the American Association for Cancer Research Annual Meeting, Apr. 1-5, 2000.
Computational Modeling of Drug Exposure Versus Antitumor Effects for Ro 31-7453, Ke, J. et al.,Proceedings of the American Association for Cancer Research Annual Meeting, Apr. 1-5, 2000.
Antitumor Efficacy and Pharmacokinetic Profile of Ro 31-7453 by Continuous Infusion in Nude Mice Bearing Human Tumor Xenografts, Cao, S. et al.Proceedings of the American Association for Cancer Research Annual Meeting, Apr. 1-5, 2000.
Weekly Paclitaxel in the Management of Ovarian Cancer [Review] Markman, M. Seminars in Oncology vol. 27 (3 Suppl 7): 37-40, 2000.
J. Natl. Cancer Inst. vol. 81(13) pp. 988-994 (Jul. 5, 1989).
A Novel Cell Cycle Inhibitor (Ro 31-7453): A Clinical And Pharmacokinetic Study in Patients with Solid Tumors, Soignet, S. et al.,Proceedings of the American Association for Cancer Research Annual Meeting, Nov., 2000.
A Clinical and Pharmacokinetic Study of a Novel Cell Cycle Inhibitor (Ro 31-7453) In Patients with Solid Tumors, Soignet, S., et al.,Proceedings of the American Association for Cancer Research Annual Meeting, Apr. 1-5, 2000.
Characterization of in vitro Antiproliferative Activity of Ro 31-7453, A New Cell-Cycle Inhibitor, Dhingra, U. et al.,Proceedings of the American Association for Cancer Research Annual Meeting, Apr. 1-5, 2000.
Ro 31-7453 has in vivo Antitumor Activity Against Human Xenograft and Syngeneic Tumor Models, Dhingra, U. et al.,Proceedings of the American Association for Cancer Research Annual Meeting, Apr. 1-5, 2000.
Preclinical Characterization of RO 31-7453, A New Cell Cycle Inhibitor, S. Ritland et al.,Proceedings of the European Spring Oncology Conference, Apr. 2000.
Breimer Lars Holger
Dhingra Kapil
Dhingra Urvashi Hooda
Ritland Steve
Hoffmann-La Roche Inc.
Johnston George W.
Reamer James H.
Rocha-Tramaloni Patricia S.
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