Non-anthracycline and dose-attenuated immunochemotherapy regimen (R-daCVP) in frail and highly elderly patients older than 70years with later stage of diffuse large B-cell lymphoma

Abstract

Introduction: Combination chemotherapy of R-CHOP is the standard treatment for patients with diffuse large B-cell lymphoma (DLBL) even in elderly patients. Patients with DLBL who are elderly and have poor performance status (≥ ECOG PS 2) are difficult to treatwith a full course of R-CHOP therapy. Objectives:We have tried to treat these advanced and poor performance status of elderly DLBL patients with rituximab and dose attenuated chemotherapy without anthracycline. (R-daCVP) We retrospectively evaluated the efficacy and safety of the R-daCVP chemotherapy in these patients. Methods: From January 1, 2005 to December 31, 2011, newly diagnosed stage III-IV DLBL patients who were considered inappropriate to receive standard R-CHOP chemotherapy were enrolled in this study. The inclusion criteria of our study were as follows; diagnosis of DLBL that was confirmed by histological examination in patients aged ≥70 years and poor performance status (PS) (ECOG PS ≥2). Patients received rituximab 375 mg/m on day 1 of each cycle. Dose attenuated CVP consisted of cyclophosphamide 600 mg/m and vincristine 1 mg/ m (maximum 2 mg) that were given intravenously on day 1 and oral prednisolone 80 mg on days 1–5. The treatment was repeated every 3 weeks and it was continued for six or eight cycles, with withdrawal due to toxicity or disease progression. Chemotherapy dosemodification was done by assessment of toxicities according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0. Results: We finally analyzed 13 patients. The median age was 78 years (range, 71-82). The distribution of the ECOG performance status was as follows: five patients (38.5%) with a performance status of 2, 8 patients (61.5%) with a performance status of 3. Eight patients (61.5%) were stage IV. Only 3 patients showed complete responses. Severe and fatal toxicity was significantly higher among these patients treated with even this less aggressive therapy. Four patients died due to grade 4 hematologic toxicities (grade 4 thrombocytopenia and grade 4 febrile neutropenia). Conclusion: In our study, we could not demonstrate that nonanthracycline dose attenuated combination immunochemotherapy with rituximab may have good potential in elderly DLBL patients with a poor PS. Eldely patients tend to have lower haemoglobin, leukocyte and platelet levels and may suffer greater toxicity from myelosuppressive chemotherapy. Careful toxicity monitoring and controlling the dose intensity or density may be needed in these fragile patients. Further studies are clearly warranted to identify the optimal management strategies for fragile and elderly patients with advanced DLBL.