Phase II study of oral fludarabine in combination with rituximab for relapsed indolent B‐cell non‐Hodgkin lymphoma

Oral fludarabine is more convenient than intravenous fludarabine in an outpatient setting. To assess the efficacy and toxicity of oral fludarabine in combination with rituximab in patients with relapsed indolent B‐cell non‐Hodgkin lymphoma (B‐NHL), we conducted a multicenter phase II study. Patients with relapsed indolent B‐NHL with two or fewer prior regimens and up to 16 doses of rituximab were eligible. Patients received 375 mg/m2 rituximab on day 1, and 40 mg/m2 oral fludarabine once daily on days 1 through 5 every 28 days for up to six cycles. The primary endpoint was the overall response rate. Forty‐one patients were enrolled, including 38 (93%) with follicular lymphoma. Thirty‐four patients (83%) had received rituximab as prior therapy. Twenty‐seven patients (66%) completed the planned six cycles. Dose reduction of oral fludarabine was required in 17 patients (41%). The overall response rate was 76% (31 of 41 patients; 95% confidence interval, 60–88%) with a complete response rate of 68% (28 of 41 patients; 95% confidence interval, 52–82%). Median progression‐free survival for the 41 patients was 19.7 months (95% confidence interval, 12.3–26.5 months). Hematological toxicities, including grade 4 neutropenia (68%), were the most frequent toxicities. Non‐hematological toxicities were mild, except for one patient who died of Pneumocystis jiroveci pneumonia 4 months after the protocol treatment. In conclusion, oral fludarabine in combination with rituximab is a highly effective and convenient therapy for patients with relapsed indolent B‐NHL who have mostly been pretreated with rituximab. (ClinicalTrials.gov number, NCT00311129.) (Cancer Sci 2009; 100: 1951–1956)