The objective of this proposal is to develop novel, laboratory-based chemotherapeutic treatment strategies for patients with cancers of the breast, lung, and ovary. This goal will be pursued through the formation of a consortium of molecular pharmacologists and clinical investigators from two NCI-designated Cancer Centers and a large University Hospital who will utilize the extensive patient resources of the City of Hope National Medical Center (COH), the Kenneth Norris, Jr. Comprehensive Cancer Center at the University of Southern California (USC), and the University of California, Davis Cancer Center (UCD) to perform pharmacologically-guided Phase II clinical trials that focus on: a) novel high-dose chemotherapies with peripheral blood progenitor cell reinfusion, the molecular pharmacodynamics of the folate-fluoropyrimidine interaction, and combination anthracycline resistance modulation studies for patients with advanced breast cancer; b) modification of intrinsic platinum resistance, chemotherapy dose intensification, new agent development, and clinical radiation sensitization for individuals suffering from small cell and non- small cell lung cancer; and c) targeted intraperitoneal and high-dose chemotherapy investigations for women with cancer of the ovary. This application formalizes an ongoing series of collaborative interactions among these three institutions that have existed since the mid-1980's. Based on the availability of over 6,250 new cancer patients per year (including 710 with breast cancer, 594 with lung cancer, and 157 with ovarian cancer in 1991), and on the major strengths of the consortium in the areas of bone marrow transplantation, the clinical pharmacodynamics of the fluoropyrimidines and the antifols, as well as pioneering experience in the quantitation of relative gene expression from small amounts of human tumor tissue, the biochemical pharmacology of the anthracyclines and platinum compounds, and clinical research strengths in regional chemotherapy, the development of novel treatment regimens, and biostatistics and data management, the COH-USC-UCD Phase II Consortium is well-positioned to utilize its clinical research expertise to perform complex, laboratory-supported investigations of both new agents and new strategies to enhance therapeutic outcomes for patients with cancers of the breast, lung, and ovary.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01CA063265-04S1
Application #
2823971
Study Section
Special Emphasis Panel (SRC (62))
Program Officer
Arbuck, Susan
Project Start
1994-06-30
Project End
2001-07-31
Budget Start
1997-04-17
Budget End
2001-07-31
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
Name
City of Hope/Beckman Research Institute
Department
Type
DUNS #
City
Duarte
State
CA
Country
United States
Zip Code
91010
Morgan Jr, Robert J; Leong, Lucille; Chow, Warren et al. (2012) Phase II trial of bryostatin-1 in combination with cisplatin in patients with recurrent or persistent epithelial ovarian cancer: a California cancer consortium study. Invest New Drugs 30:723-8
Morgan Jr, R J; Synold, T W; Gandara, D et al. (2007) Phase II trial of carboplatin and infusional cyclosporine with alpha-interferon in recurrent ovarian cancer: a California Cancer Consortium Trial. Int J Gynecol Cancer 17:373-8
Lara Jr, Primo N; Law, Lisa Y; Wright, John J et al. (2005) Intermittent dosing of the farnesyl transferase inhibitor tipifarnib (R115777) in advanced malignant solid tumors: a phase I California Cancer Consortium Trial. Anticancer Drugs 16:317-21
Openshaw, Harry; Beamon, Karen; Longmate, Jeffrey et al. (2005) The effect of height on paclitaxel nerve damage. J Neurooncol 74:207-10
Lara Jr, Primo N; Mack, Philip C; Synold, Timothy et al. (2005) The cyclin-dependent kinase inhibitor UCN-01 plus cisplatin in advanced solid tumors: a California cancer consortium phase I pharmacokinetic and molecular correlative trial. Clin Cancer Res 11:4444-50
Lara Jr, Primo N; Gumerlock, Paul H; Mack, Philip C et al. (2004) Gemcitabine in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy: a phase II California cancer consortium trial. Clin Lung Cancer 6:102-7
Morgan Jr, Robert J; Synold, Timothy W; Gandara, David et al. (2004) Phase II trial of carboplatin and infusional cyclosporine in platinum-resistant recurrent ovarian cancer. Cancer Chemother Pharmacol 54:283-9
Openshaw, Harry; Beamon, Karen; Synold, Timothy W et al. (2004) Neurophysiological study of peripheral neuropathy after high-dose Paclitaxel: lack of neuroprotective effect of amifostine. Clin Cancer Res 10:461-7
Lara Jr, Primo N; Chee, Karen Giselle; Longmate, Jeff et al. (2004) Trastuzumab plus docetaxel in HER-2/neu-positive prostate carcinoma: final results from the California Cancer Consortium Screening and Phase II Trial. Cancer 100:2125-31
Lara Jr, Primo N; Frankel, Paul; Mack, Philip C et al. (2003) Tirapazamine plus carboplatin and paclitaxel in advanced malignant solid tumors: a california cancer consortium phase I and molecular correlative study. Clin Cancer Res 9:4356-62

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