Abstract | BACKGROUND: PATIENTS AND METHODS: We report on a phase I study of Salirasib in patients with relapsed/refractory hematologic malignancies. Salirasib was administered orally twice daily on days 1 to 21 of a 28-day cycle in a "3+3" dose escalation design. RESULTS: Seventeen patients with relapsed/refractory leukemia were treated for a median of 4 cycles (range, 1-29). Three patients each were enrolled at a dose level of 100, 200, 400, 600, and 800 mg twice daily and 2 patients at a dose level of 900 mg twice daily. No dose-limiting toxicities were encountered. Grade 1/2 diarrhea was the only frequent nonhematologic toxicity observed in 14 of 17 (82%) patients and was resolved with oral antidiarrheal agents. Eight (47%) patients (4 with myelodysplastic syndrome, 2 with acute myeloid leukemia, 1 with chronic myelomonocytic leukemia, and 1 with chronic myeloid leukemia) had hematological improvement; 1 in 3 lineages, 1 in 2 lineages, and 6 in 1 lineage. None of the patients achieved complete remission. The responses lasted for a median of 10 weeks (range, 5-115). The study was discontinued because of financial constraints. CONCLUSION:
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Authors | Talha Badar, Jorge E Cortes, Farhad Ravandi, Susan O'Brien, Srdan Verstovsek, Guillermo Garcia-Manero, Hagop Kantarjian, Gautam Borthakur |
Journal | Clinical lymphoma, myeloma & leukemia
(Clin Lymphoma Myeloma Leuk)
Vol. 15
Issue 7
Pg. 433-438.e2
(Jul 2015)
ISSN: 2152-2669 [Electronic] United States |
PMID | 25795639
(Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 Elsevier Inc. All rights reserved. |
Chemical References |
- Antineoplastic Agents
- Salicylates
- farnesylthiosalicylic acid
- Farnesol
- raf Kinases
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Antineoplastic Agents
(administration & dosage, therapeutic use)
- Farnesol
(administration & dosage, analogs & derivatives, therapeutic use)
- Female
- Genes, ras
(drug effects)
- Humans
- Leukemia
(drug therapy)
- Male
- Middle Aged
- Neoplasm Recurrence, Local
(drug therapy)
- Salicylates
(administration & dosage, therapeutic use)
- Signal Transduction
(drug effects)
- Transcriptional Activation
(drug effects)
- Treatment Outcome
- raf Kinases
(antagonists & inhibitors)
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