Fludarabine phosphate–CVP in patients over 60 years of age with advanced, low-grade and follicular lymphoma: A dose-finding study Pierre Soubeyran * , Alain Monnereau, Houchingue Eghbali, Isabelle Soubeyran, Miche `le Kind, Laurent Cany, Elizabeth Buy, Odile Guibon, Bernard Hœrni The Institute Bergonie ´, Regional Cancer Center, 229 cours de lÕArgonne, 33076 Bordeaux Cedex, France and Schering AG, Lys Lez Lannoy, France Received 24 November 2004; received in revised form 19 August 2005; accepted 23 August 2005 Available online 25 October 2005 Abstract 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-HodgkinÕs 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 20 mg/m 2 , respectively (Days 1–5); C, 750 and 500 mg/m 2 , respectively (Day 1); and V, 1.4 and 1 mg/m 2 , respectively (Day 1). Patients received P at 40 mg/m 2 on Days 1–5. Response was assessed after Cycles 2, 4, 6 and 8. At level 3, dose-limiting toxicity (opportunistic infections and neutro- penia) 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 fea- sible and increased the CR rate, with good tolerability in elderly patients. Ó 2005 Elsevier Ltd. All rights reserved. Keywords: Fludarabine phosphate; Non-HodgkinÕs lymphoma; Follicular lymphoma 1. Introduction Elderly patients with advanced, low-grade and follicu- lar non-HodgkinÕs lymphoma (NHL) have incurable dis- ease with poor prognostic factors at the time of diagnosis [1,2]. For asymptomatic patients, a Ôwait-and-seeÕ ap- proach does not appear to modify the prognosis [3–5]. In symptomatic patients, conventional chemotherapy, based on alkylating agents, is ineffective in the long term [6], and more successful treatment strategies are needed. Single-agent fludarabine phosphate (Fludara Ò ) is a safe and effective therapy for NHL [7–10], and is well tolerated in elderly patients [11]. As a front-line therapy, fludarabine phosphate can achieve overall response rates (ORRs) of up to 84% [12], with good complete response (CR) rates (from 34% to 47%) [10–13]. Particularly high CR rates have been recorded in patients with follicular lymphoma (up to 60% in one trial) [12]. Fludarabine phosphate provides a good basis for combination thera- pies because of its more acceptable safety profile in com- parison with alkylating agents [14]. Additionally, in vitro data support a synergistic effect of fludarabine phos- phate and alkylating agents when used in combination [15,16]. 0959-8049/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.ejca.2005.08.021 * Corresponding author. Tel.: +33 556 33 32 67; fax: +33 5 556 33 33 83. E-mail address: soubeyran_p@bergonie.org (P. Soubeyran). www.ejconline.com European Journal of Cancer 41 (2005) 2630–2636 European Journal of Cancer