Gemcitabine, ifosfamide, oxaliplatin and rituximab (R-GIFOX), a new effective cytoreductive/mobilizing salvage regimen for relapsed and refractory aggressive non-Hodgkin's lymphoma: results of a pilot study.

BACKGROUND: The prognosis of patients with aggressive non-Hodgkin's lymphoma (NHL) relapsing or progressing after front-line therapy remains poor. Since high-dose therapy (HDT) with autologous stem cell transplantation (ASCT) can cure a proportion of such patients, provided that a substantial tumor shrinkage is achieved, the development of more effective and less toxic salvage regimens remains a major challenge. We evaluated the clinical activity, toxicity and mobilizing capacity of a new salvage regimen, which combines gemcitabine and oxaliplatin with ifosfamide and rituximab (R-GIFOX) in patients with relapsed and refractory CD20(+) NHL.

PATIENTS AND METHODS: Patients were scheduled to receive three courses of therapy followed by mobilization and ASCT or three more courses if ineligible for ASCT. R-GIFOX consisted of rituximab (375 mg/m(2) on day 1), gemcitabine (1000 mg/m(2) on day 2), oxaliplatin (130 mg/m(2) on day 3) and ifosfamide (5 g/m(2) on day 3) as a 24-h single infusion in patients aged < or =65 years, or fractionated over 3 days (days 3-5) in patients aged >65 years. Treatment was given every 2 weeks with G-CSF support (5 microg/kg/day or 10 microg/kg/day at the end of the third course for stem cell mobilization). Responses were evaluated by the integrated FDG-PET/IWC criteria after the third course and at the end of the entire program.

RESULTS: Fourteen patients (median age 63 years, range 37-78 years) with relapsed (n = 9) or primary progressive (n = 5) aggressive (diffuse large cell, mantle cell, follicular G3), advanced (stage IV 71%), poor risk (IPI 3-5 50%) NHL were accrued in this pilot study. Patients had received a median of two previous treatment lines (range 1-4). The median number of R-GIFOX courses delivered was 4 (range 1-6). Thirteen patients completed at least three courses of therapy and were evaluable for response. The overall response rate assessed after three courses of R-GIFOX was 77%, with seven complete responses and three partial responses. Effective CD34(+) cell mobilization was obtained in four of six eligible patients and two had ASCT. Hematologic and extra-hematologic toxicity was tolerable. Failure-free survival was 79.6% at median follow-up of 6 months (range 2-12). Molecular remissions were documented in two patients with mantle cell NHL.

CONCLUSIONS: Based on the results of this pilot study, we conclude that the R-GIFOX regimen is feasible, tolerable, effective and able to mobilize peripheral stem cells in patients with relapsed and refractory aggressive NHL.