Title:
METHOD OF TREATING HEMATOLOGIC TUMORS AND CANCERS USING BETA LAPACHONE
Document Type and Number:
WIPO Patent Application WO2002058694
Kind Code:
A3
Abstract:
Multiple myeloma and other hematologic tumors and/or malignancies can be treated by administration of a G1 and/or S phase drug, which is preferably beta-lapachone, or a derivative or analog thereof, combined with a G2/M phase drug such as taxane derivative, which is advantageously paclitaxel. This combination of the G1 and/or S phase drug with the G2/M phase drug results in an unexpectedly greater than additive (i.e., synergistic) apoptosis in multiple myeloma cells. The invention includes methods of treating multiple myeloma by administering the combination of the G1 and/or S phase drug and the G2/M phase drug, pharmaceutical compositions comprising the combination of drugs used in these methods, as well as pharmaceutical kits.
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Inventors:
PARDEE ARTHUR B (US)
ANDERSON KENNETH (US)
GUPTA DEEPAK (US)
LI CHIANG (US)
LI YOUZHI (US)
ANDERSON KENNETH (US)
GUPTA DEEPAK (US)
LI CHIANG (US)
LI YOUZHI (US)
Application Number:
PCT/US2001/049946
Publication Date:
December 04, 2003
Filing Date:
November 07, 2001
Export Citation:
Assignee:
DANA FARBER CANCER INST INC (US)
PARDEE ARTHUR B (US)
ANDERSON KENNETH (US)
GUPTA DEEPAK (US)
LI CHIANG (US)
LI YOUZHI (US)
PARDEE ARTHUR B (US)
ANDERSON KENNETH (US)
GUPTA DEEPAK (US)
LI CHIANG (US)
LI YOUZHI (US)
International Classes:
C07D311/92; A61K31/00; A61K31/337; A61K31/352; A61K31/4745; A61K31/704; A61K31/7048; A61K45/00; A61K45/06; A61K47/10; A61K47/32; A61K47/34; A61K47/40; A61P35/00; A61P35/02; (IPC1-7): A61K31/352; A61K45/06; A61P35/02
Domestic Patent References:
| WO1994004145A1 | 1994-03-03 | |||
| WO1997008162A1 | 1997-03-06 | |||
| WO1997031936A2 | 1997-09-04 | |||
| WO1996033988A1 | 1996-10-31 |
Other References:
DATABASE MEDLINE [online] US NATIONAL LIBRARY OF MEDICINE (NLM), BETHESDA, MD, US; 1 September 1995 (1995-09-01), PLANCHON S M ET AL: "Beta-lapachone-mediated apoptosis in human promyelocytic leukemia (HL-60) and human prostate cancer cells: a p53-independent response.", XP002241805, Database accession no. NLM7641180
ZHANG W ET AL: "The induction of apoptosis and cell cycle arrest by arsenic trioxide in lymphoid neoplasms.", LEUKEMIA: OFFICIAL JOURNAL OF THE LEUKEMIA SOCIETY OF AMERICA, LEUKEMIA RESEARCH FUND, U.K. ENGLAND SEP 1998, vol. 12, no. 9, September 1998 (1998-09-01), pages 1383 - 1391, XP002110654, ISSN: 0887-6924
GAZITT Y ET AL: "Bcl-2 overexpression is associated with resistance to paclitaxel, but not gemcitabine, in multiple myeloma cells.", INTERNATIONAL JOURNAL OF ONCOLOGY. GREECE OCT 1998, vol. 13, no. 4, October 1998 (1998-10-01), pages 839 - 848, XP008016801, ISSN: 1019-6439
LI Y ET AL: "Potent induction of apoptosis by beta - lapachone in human multiple myeloma cell lines and patient cells.", MOLECULAR MEDICINE, (2000 DEC) 6 (12) 1008-15., XP008016797
ZHANG W ET AL: "The induction of apoptosis and cell cycle arrest by arsenic trioxide in lymphoid neoplasms.", LEUKEMIA: OFFICIAL JOURNAL OF THE LEUKEMIA SOCIETY OF AMERICA, LEUKEMIA RESEARCH FUND, U.K. ENGLAND SEP 1998, vol. 12, no. 9, September 1998 (1998-09-01), pages 1383 - 1391, XP002110654, ISSN: 0887-6924
GAZITT Y ET AL: "Bcl-2 overexpression is associated with resistance to paclitaxel, but not gemcitabine, in multiple myeloma cells.", INTERNATIONAL JOURNAL OF ONCOLOGY. GREECE OCT 1998, vol. 13, no. 4, October 1998 (1998-10-01), pages 839 - 848, XP008016801, ISSN: 1019-6439
LI Y ET AL: "Potent induction of apoptosis by beta - lapachone in human multiple myeloma cell lines and patient cells.", MOLECULAR MEDICINE, (2000 DEC) 6 (12) 1008-15., XP008016797
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