Fludarabine phosphate–CVP in patients over 60 years of age with advanced, low-grade and follicular lymphoma: A dose-finding study

The aim of this study was to establish a safe and effective regimen of fludarabine phosphate, cyclophosphamide, vincristine and prednisone (F–CVP) as first-line treatment for elderly patients with advanced, low-grade non-Hodgkin’s lymphoma. Twenty-three patients >60 years were assigned successively to eight treatment cycles (Dose level 1: low F, low CV [n=4]; 2A: high F, low CV [n=8]; 2B: low F, high CV [n=4]; 3: high F, high CV [n=7]). High and low levels were: F, 25 and 20mg/m2, respectively (Days 1–5); C, 750 and 500mg/m2, respectively (Day 1); and V, 1.4 and 1mg/m2, respectively (Day 1). Patients received P at 40mg/m2 on Days 1–5. Response was assessed after Cycles 2, 4, 6 and 8. At level 3, dose-limiting toxicity (opportunistic infections and neutropenia) became evident, particularly after Cycle 6. Further patients were recruited at Dose level 2A. All regimens proved effective, with an OR rate of 78% (65% CR), and 3-year survival of 65% (±10%). Among 18 responders, 51% were still in response at 3 and 5 years. The study shows that this combination therapy is highly effective. The addition of F to CVP at Dose level 2A was feasible and increased the CR rate, with good tolerability in elderly patients.