Abstract | BACKGROUND: METHODS: Twenty-six patients (13 [50%] with Abl kinase domain mutations) were treated. The initial dose level was tipifarnib at a dose of 300 mg twice daily and imatinib at a dose of 300 mg daily. Therapy was escalated following a '3 + 3' phase 1 design and the maximum tolerated dose was defined as tipifarnib at a dose of 400 mg twice daily and imatinib at a dose of 400 mg daily. Therapy was administered for a median of 26 weeks (range, 3-150 weeks). RESULTS: Adverse events included diarrhea in 21 patients (81%) and nausea in 18 patients (69%), but were generally grade 2 or less (using the revised National Cancer Institute Common Toxicity Criteria). Grade 3-4 neutropenia and thrombocytopenia occurred in 11 patients (42%) and 8 patients (31%), respectively. Sixteen patients discontinued therapy (5 due to toxicity and 11 due to lack of response or disease progression). Hematologic responses were attained by 17 (68%) of 25 assessable patients. Nine patients (36%) also achieved a cytogenetic response (3 complete responses, 4 partial responses, and 2 minimal responses), including 4 patients harboring mutant Bcr-Abl tyrosine kinases. One patient bearing the highly imatinib-resistant T315I mutant achieved a partial cytogenetic response. The median response duration was 3 months (range, 2-30+ months). CONCLUSIONS:
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Authors | Jorge Cortes, Alfonso Quintás-Cardama, Guillermo Garcia-Manero, Susan O'Brien, Dan Jones, Stefan Faderl, Theresa Ebarb, Francis Giles, Deborah Thomas, Hagop Kantarjian |
Journal | Cancer
(Cancer)
Vol. 110
Issue 9
Pg. 2000-6
(Nov 01 2007)
ISSN: 0008-543X [Print] United States |
PMID | 17849425
(Publication Type: Clinical Trial, Phase I, Journal Article)
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Chemical References |
- Benzamides
- Piperazines
- Pyrimidines
- Quinolones
- Imatinib Mesylate
- Fusion Proteins, bcr-abl
- tipifarnib
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Antineoplastic Combined Chemotherapy Protocols
(adverse effects)
- Benzamides
- Dose-Response Relationship, Drug
- Drug Resistance, Neoplasm
- Fusion Proteins, bcr-abl
(drug effects)
- Humans
- Imatinib Mesylate
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
(drug therapy)
- Maximum Tolerated Dose
- Middle Aged
- Piperazines
(administration & dosage, adverse effects)
- Pyrimidines
(administration & dosage, adverse effects)
- Quinolones
(administration & dosage, adverse effects)
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