Abstract

This proposal originally encompassed 3 discrete projects comprised of the following items: clinical/pharmacologic studies of all- trans retinoic acid (RA) in acute promyelocytic leukemia (APL) to include an evaluation of mechanisms and means of overcoming acquired clinical resistance; 2) use of a newly developed polymerase chain reaction assay for the molecular marker of APL (fusion of the retinoic acid receptor-alpha with the PML gene) as a means of detecting and monitoring disease activity during complete remission (CR); and 3) use of anti-CD33 monoclonal antibodies as a means of eradicating minimal residual disease after CR. The monoclonal antibody project was eliminated in peer review by the study section, and the tentative award for the remaining two-thirds of the application was administratively reduced by 50%, leaving sufficient funds for one-third of the original project. Based on the study section critique, only project #1 (clinical pharmacology) will be conducted under this grant.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA057645-01
Application #
3202000
Study Section
Experimental Therapeutics Subcommittee 1 (ET)
Project Start
1992-09-01
Project End
1995-08-31
Budget Start
1992-09-01
Budget End
1993-08-31
Support Year
1
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

Soignet, S; Fleischauer, A; Polyak, T et al. (1997) All-trans retinoic acid significantly increases 5-year survival in patients with acute promyelocytic leukemia: long-term follow-up of the New York study. Cancer Chemother Pharmacol 40 Suppl:S25-9
Rigas, J R; Miller, V A; Zhang, Z F et al. (1996) Metabolic phenotypes of retinoic acid and the risk of lung cancer. Cancer Res 56:2692-6
Miller, V A; Rigas, J R; Benedetti, F M et al. (1996) Initial clinical trial of the retinoid receptor pan agonist 9-cis retinoic acid. Clin Cancer Res 2:471-5
Vyas, R C; Frankel, S R; Agbor, P et al. (1996) Probing the pathobiology of response to all-trans retinoic acid in acute promyelocytic leukemia: premature chromosome condensation/fluorescence in situ hybridization analysis. Blood 87:218-26
Jurcic, J G; Caron, P C; Miller Jr, W H et al. (1995) Sequential targeted therapy for relapsed acute promyelocytic leukemia with all-trans retinoic acid and anti-CD33 monoclonal antibody M195. Leukemia 9:244-8
Dyck, J A; Warrell Jr, R P; Evans, R M et al. (1995) Rapid diagnosis of acute promyelocytic leukemia by immunohistochemical localization of PML/RAR-alpha protein. Blood 86:862-7
Miller Jr, W H; Jakubowski, A; Tong, W P et al. (1995) 9-cis retinoic acid induces complete remission but does not reverse clinically acquired retinoid resistance in acute promyelocytic leukemia. Blood 85:3021-7
Eardley, A M; Heller, G; Warrell Jr, R P (1994) Morbidity and costs of remission induction therapy with all-trans retinoic acid compared with standard chemotherapy in acute promyelocytic leukemia. Leukemia 8:934-9
Vahdat, L; Maslak, P; Miller Jr, W H et al. (1994) Early mortality and the retinoic acid syndrome in acute promyelocytic leukemia: impact of leukocytosis, low-dose chemotherapy, PMN/RAR-alpha isoform, and CD13 expression in patients treated with all-trans retinoic acid. Blood 84:3843-9
Warrell Jr, R P; Maslak, P; Eardley, A et al. (1994) Treatment of acute promyelocytic leukemia with all-trans retinoic acid: an update of the New York experience. Leukemia 8:929-33

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