Cyclophosphamide and doxorubicin, two important drugs in the treatment of lymphoma, exhibit a relationship between dose and fractional cell kill, and because of their toxicity profiles, they are candidates for significant dose escalation. We performed a phase II trial to determine the response rate, toxicity, and feasibility of escalated doses of both drugs as part of high dose CHOP in diffuse aggressive lymphoma. Patients who had advanced, previously untreated diffuse aggressive lymphomas (IWF E-H) and an International Prognostic Index of intermediate to high risk were eligible. Treatment was cyclophosphamide 2 m/m2/day intravenously on Days 1 and 2 (total cycle dose 4 m/m2), doxorubicin 35 mg/m2/day as a continuous infusion on Days 1 and 2 (total 70 mg/m2), vincristine 1.4 mg/m2 (maximum 2 mg) on Day 1 and prednisone 100 mg/day orally on Days 1-5 repeated every 3 weeks for a total of four cycles. G-CSF, prophylactic antibiotics, and mesna were provided. A total of 99 patients were enrolled; 98 received therapy. Major toxicities were Grade 4 neutropenia and thrombocytopenia occurring in 97% and 92%, respectively. Serious infections occurred in 53%. Treatment-related mortality was 2%. The overall response rate is 85%, and two-year failure free and overall survival are 39% and 64%, respectively. Persistent or relapsed lymphoma was the overwhelming cause of death. Six patients have developed AML or MDS. In view of the substantial toxicity accompanying high dose CHOP, the observed outcome suggests that its efficacy is not sufficient to make further study feasible.
Bibliographical noteFunding Information:
This research was supported, in part, by grants from the National Cancer Institute (CA31946) to the Cancer and Leukemia Group B (Richard L. Schilsky, MD, Chairman). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. Jeffrey Johnson was supported by CA33601, Margaret A. Shipp and George P. Canellos by CA32291, Maurice Barcos by CA02599, and Jon P. Gockerman by CA47577.
- Diffuse aggressive lymphoma