التفاصيل البيبلوغرافية
| العنوان: |
A Phase 1 and 2 study of Filanesib alone and in combination with low-dose dexamethasone in relapsed/refractory multiple myeloma. |
| المؤلفون: |
Shah, Jatin J.1, Kaufman, Jonathan L.2, Zonder, Jeffrey A.3, Cohen, Adam D.4, Bensinger, William I.5, Hilder, Brandi W.6, Rush, Selena A.6, Walker, Duncan H.6, Tunquist, Brian J.6 btunquist@arraybiopharma.com, Litwiler, Kevin S.6, Ptaszynski, Mieke6, Orlowski, Robert Z.1, Lonial, Sagar2 |
| المصدر: |
Cancer (0008543X). Dec2017, Vol. 123 Issue 23, p4617-4630. 15p. |
| مصطلحات موضوعية: |
*DEXAMETHASONE, *MULTIPLE myeloma, *BORTEZOMIB, *GRANULOCYTE-colony stimulating factor, *PATIENTS, *THERAPEUTICS, *ANTINEOPLASTIC agents, *CANCER relapse, *CLINICAL trials, *COMPARATIVE studies, *DRUG resistance in cancer cells, *DRUG dosage, *DRUG toxicity, *LONGITUDINAL method, *RESEARCH methodology, *MEDICAL cooperation, *PROGNOSIS, *RESEARCH, *RESEARCH funding, *SURVIVAL, *THIAZOLES, *EVALUATION research, *SALVAGE therapy |
| مستخلص: |
Background: Filanesib (ARRY-520) is a highly selective inhibitor of kinesin spindle protein, which has demonstrated preclinical antimyeloma activity.Methods: This open-label Phase 1/2 study determined the maximum tolerated dose of Filanesib administered on Days 1 and 2 of 14-Day Cycles in patients with multiple myeloma (MM) and included expansion cohorts with and without dexamethasone (40 mg/week). Patients in the dose-escalation (N = 31) and Phase 2 single-agent (N = 32) cohorts had received prior bortezomib as well as prior thalidomide and/or lenalidomide. Patients in the Phase 2 Filanesib plus dexamethasone cohort (N = 55) had received prior alkylator therapy and had disease refractory to lenalidomide, bortezomib, and dexamethasone. Prophylactic filgrastim was incorporated during dose escalation and was used throughout Phase 2.Results: Patients in each cohort had received a median of ≥6 prior therapies. The most common dose-limiting toxicities were febrile neutropenia and mucosal inflammation. In Phase 2, Grade 3 and 4 cytopenias were reported in approximately 50% of patients. Nonhematologic toxicities were infrequent. Phase 2 response rates (partial responses or better) were 16% (single agent) and 15% (Filanesib plus dexamethasone). All responding patients had low baseline levels of α1-acid glycoprotein, a potential selective biomarker.Conclusions: Filanesib 1.50 mg/m2 /day administered with prophylactic filgrastim has a manageable safety profile and encouraging activity in heavily pretreated patients This study is registered at www.clinicaltrials.gov as NCT00821249. Cancer 2017;123:4617-4630. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR] |
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