Rituximab, Gemcitabine and Oxaliplatin (R-GEMOX): A Promising Regimen for Refractory/Relapsed B-Cell Lymphoma.

Background : High-dose therapy with autologous stem cell support (HDT) is an established treatment for chemosensitive relapse in aggressive lymphoma. However, not all patients are candidates for HDT because of age, comorbidities or previous HDT. Effective and well tolerated salvage therapies with minimal toxicities are thus needed.

Methods : We designed the R-GEMOX regimen, with rituximab 375mg/m2 d1, gemcitabine 1000 mg/m2 d2 and oxaliplatin 100 mg/m2 d2 (recycling on d15). Between January 2002 and April 2004, 31 patients with refractory/relapsing B-cell lymphoma not eligible for HDT were enrolled in an open unicenter pilot study whose primary objective was to determine the overall response rate (ORR) after 4 cycles (induction phase) of R-GEMOX. Patients were planned to receive 8 cycles if a good response (at least PR) was observed after 4 cycles. Median age was 63 years (range: 43–77) and histological subtypes were : diffuse large B-cell lymphoma (n=22), follicular (n=6) and mantle cell (n=3). Prior treatment included anthracyclin in 30 patients (98%), rituximab in 16 (52%) and HDT in 8 (26%). International prognostic index at enrollment was ≥ 2 in 13 patients (42%). The median number of prior treatments was 2 (range : 1 to 5) and 9 patients had received at least 3 prior regimens.

Results : 226 cycles were given. The dose administered was 100% of the intended dose for the three drugs in all patients but 6, for whom the dose of oxaliplatin was reduced due to neurotoxicity (n=5) or preexisting renal insufficiency (n=1). The median number of cycles per patient was 8 (range: 2–8).Three patients progressed during the induction phase. After 4 cycles, observed responses were : 6 CR, 8 CRu, 12 PR and 2 failures resulting in an ORR of 84 %. At the end of treatment, among the 26 responder-patients at 4 cycles, 23 patients achieved CR/CRu and one patient progressed. As of August 2004, 22 patients are alive, 17 in continuous complete remission and 5 with evolutive disease. NCIC grade 3–4 neutropenia and thrombocytopenia were reported in 49% and 23% of the cycles. Six patients developed a grade 4 infection during one cycle. There was no renal toxicity.

Conclusion : The R-GEMOX regimen shows promising activity with an acceptable toxicity. It is currently evaluated in an ongoing multicentric phase II study on diffuse large B-cell lymphoma patients at first relapse. (=69.03% taille max abstract)