Rigosertib in combination with azacitidine in patients with myelodysplastic syndromes or acute myeloid leukemia: Results of a phase 1 study
| Autor: | Shyamala C. Navada, Patrick S. Zbyszewski, Richard C. Woodman, Naveen Pemmaraju, Rosmy B. John, Guillermo Garcia-Manero, Lewis R. Silverman, Erin P. Demakos, Rosalie Odchimar-Reissig, Steven M. Fruchtman, Maro Ohanian, Yesid Alvarado, Manoj Maniar |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male Cancer Research medicine.medical_specialty Myeloid Azacitidine Glycine Chronic myelomonocytic leukemia Gastroenterology 03 medical and health sciences 0302 clinical medicine hemic and lymphatic diseases Internal medicine Leukemia Myelogenous Chronic BCR-ABL Positive medicine Humans Sulfones Adverse effect Aged Aged 80 and over business.industry Myelodysplastic syndromes Rigosertib Myeloid leukemia Hematology Middle Aged medicine.disease Leukemia Myeloid Acute medicine.anatomical_structure Oncology Hypomethylating agent 030220 oncology & carcinogenesis Myelodysplastic Syndromes Female business 030215 immunology medicine.drug |
| Zdroj: | Leukemia research. 94 |
| ISSN: | 1873-5835 |
| Popis: | Phase 1 results from a Phase 1/2 study comprise 18 patients with myelodysplastic syndromes (MDS; n = 9), acute myeloid leukemia (AML; n = 8), and chronic myelomonocytic leukemia (CMML; n = 1) who were either hypomethylating agent naive (n = 10) or relapsed/refractory following prior hypomethylating agent therapy (n = 8) (NCT01926587). Patients received oral rigosertib, an inhibitor of Ras-effector pathways, in 3 successive cohorts (140 mg twice daily, 280 mg twice daily, or 840 mg/day [560 mg morning/280 mg evening]) for 3 weeks of a 4-week cycle. Patients received parenteral azacitidine (75 mg/m2/day × 7 days) during the second week; the cycle repeated every 4 weeks. The combination was well tolerated for a median of 4 (range 1–41) cycles, with 72% of patients experiencing ≥1 serious adverse events. No dose-limiting toxicities were observed. Thus, no maximum tolerated dose was reached. The most frequently reported adverse events were diarrhea (50%), constipation, fatigue, and nausea (each 44%), and pneumonia and back pain (each 33%). Sequential administration demonstrated an overall response rate of 56% in evaluable patients, with responses observed in 7/9 MDS/CMML patients (78%) and 2/7 AML patients (29%). Further clinical studies are warranted to investigate this doublet therapy in patients with myeloid malignancies. |
| Databáze: | OpenAIRE |
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