Cyclophosphamide, pegylated liposomal doxorubicin, vincristine and prednisone (CDOP) plus rituximab is effective and well tolerated in poor performance status elderly patients with non-Hodgkin's lymphoma

Lymphomas in elderly patients require special attention, not only for possible important co-morbidities and poor performance status, but also for diminished organ functions and altered drug metabolism, which modify the pharmacokinetics of the treatment [1]. Thus, first-line elderly non-Hodgkin’s lymphoma (NHL) patients are frequently treated with a consequent dose reduction [2,3]. Similarly, the treatment outcome of salvage therapy for relapsed/ refractory NHL patients is limited by multidrug resistance, low performance status and the high toxicity of secondand third-line regimens. Anthracycline-based regimens are extremely effective in NHL; the main disadvantage is cardiotoxicity. Pegylated liposomal doxorubicin has been shown to determine lower toxicity if compared with conventional doxorubicin, while having similar efficacy in patients with Kaposi’s sarcoma and solid tumors. Due to the prolonged half-life (nearly 43 h), it offers the opportunity of obtaining prolonged exposure of tumor cells to active concentrations, with possible effects on the disease. A recent study concluded that an improvement in the survival of elderly patients with lymphoma is related to an optimized toxicity chemotherapy schedule [4,5]. In addition, cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) plus rituximab has been demonstrated to be superior to CHOP alone in elderly patients with diffuse large cell lymphoma [6,7]. We thus tested the safety and efficacy of a regimen [cyclophosphamide, pegylated liposomal doxorubicin, vincristine and prednisone (CDOP) plus rituximab] using a pegylated liposomal doxorubicin instead of conventional doxorubicin, in order to reduce the toxic profile and preserve the dose intensity, administered as follows: day 1, cyclophosphamide 750 mg/m, pegylated liposomal doxorubicin (Caelyx, Schering Plough S.A., Italy) 40 mg/m, vincristine 1.4 mg/m, prednisone 100 mg p.o. days 1 – 5, rituximab 375 mg/ m on day 15 of every cycle; granulocyte colonystimulating factor (G-CSF) from day 10 to day 14. Therapy was repeated every 21 days for 6 cycles. Complete and partial remission were assessed as the overall response. Toxicity was evaluated according to the WHO criteria. Thirteen patients were treated (Table I); 12 (92%) completed the 6 courses and were assessable for response (Table II). A dose reduction (25%) was carried out in 2 cases (1 frail, 1 relapsed-refractory), due to their extremely altered clinical condition. Seven patients (53%) obtained complete remission, 5 (31%) partial remission, for an overall response rate of 84%. No major toxicity (WHO grade III/IV) occurred. Only 1 patient delayed therapy for grade II hematological toxicity. After a median follow-up of 18 months (range 8 – 22 months), 7 patients are in continuous complete remission (53%), 3 (23%) in partial remission, 1 in stable disease, whereas only 2 patients progressed. In our opinion, one of the reasons for the high overall response rate (84%) and of the maintenance of the response, even in this category of very fragile patients, is the respect of the doses, as well as of the