Efficacy and safety of clofarabine in relapsed and/or refractory non-Hodgkin lymphoma, including rituximab-refractory patients
| Autor: | Kathy Tolzien, Angel G. Galvez, Wendy M. Dewey, Chadi Nabhan, Walter Fried, Nancy Davis, Susan Foss, Jacob D. Bitran, Parameswaran Venugopal |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Male Cancer Research medicine.medical_specialty Salvage therapy Phases of clinical research Neutropenia Gastroenterology Disease-Free Survival Antibodies Monoclonal Murine-Derived Refractory Non-Hodgkin Lymphoma Recurrence hemic and lymphatic diseases Internal medicine medicine Clofarabine Humans Aged Aged 80 and over Salvage Therapy business.industry Adenine Nucleotides Lymphoma Non-Hodgkin Middle Aged medicine.disease Surgery Transplantation Tumor lysis syndrome Oncology Drug Resistance Neoplasm Retreatment Rituximab Female Arabinonucleosides business medicine.drug |
| Zdroj: | Cancer. 117(7) |
| ISSN: | 0008-543X |
| Popis: | BACKGROUND: Currently, no standard therapy exists for patients with relapsed and/or refractory non-Hodgkin lymphoma (NHL) who are ineligible for transplantation or who have failed after bone marrow transplantation. The authors of this report investigated the safety and efficacy of clofarabine (CLO) in these patients. METHODS: In a 2-step, open-label study, CLO (as a 1-hour intravenous infusion given daily for 5 days) was given every 28 days (maximum, 6 cycles). In the phase 1 portion (n = 7; standard 3 + 3 study design), the dose was escalated by 2 mg/m2 to determine the maximum tolerated dose (MTD). The phase 2 study (n = 26) was initiated at the MTD, and patients were followed until disease progression. RESULTS: Of 33 patients who were enrolled, 31 patients (median age, 69 years) were evaluable; 24% failed after previous stem cell transplantation, and 72% were rituximab-refractory. The MTD for CLO was 4 mg/m2. The overall response rate was 42%. Seven patients (23%) achieved a complete response, and 6 patients (19%) achieved a partial response. The median response duration was 5 months. Among the rituximab-refractory patients, the overall response rate was 47% (complete response rate, 28%), and the median response duration was 7 months. At a median follow-up of 14 months, 45% of patients remained alive (median overall survival, 10 months). Toxicity was mainly hematologic (≥60% of patients had neutropenia or thrombocytopenia). Nonhematologic toxicity included tumor lysis syndrome, infection, and renal insufficiency (in 6% of patients each). No treatment-related mortality was observed. CONCLUSIONS: Single-agent CLO was active and was tolerated well in patients with refractory NHL, including patients in a rituximab-refractory subset. Reversible myelosuppression was the major toxicity. Study is registered at www.clinicaltrials.gov (NCT00156013). Cancer 2011. © 2010 American Cancer Society. |
| Databáze: | OpenAIRE |
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