Salvage chemotherapy with temozolomide in primary CNS lymphomas: preliminary results of a phase II trial Michele Reni a, * , Warren Mason b , Francesco Zaja c , James Perry d , Enrico Franceschi e , Daniele Bernardi f , Stefania Dell’Oro a , Caterina Stelitano g , Marco Candela h , Antonio Abbadessa i , Andrea Pace j , Roberto Bordonaro k , Giancarlo Latte l , Eugenio Villa a , Andr  es J.M. Ferreri a a Department of Radiochemotherapy, S. Raffaele Hospital Scientific Institute, Milan, Italy b Princess Margaret Hospital, Toronto, Ont., Canada c Clinica Ematologica, Policlinico Universitario, Udine, Italy d Bayview Regional Cancer Center, Toronto, Ont., Canada e Department of Medical Oncology, Bellaria Hospital, Bologna, Italy f Division of Medical Oncology, National Cancer Institute, Aviano, Italy g Division of Haematology, Reggio Calabria, Italy h Clinica Medica, Torrette Hospital, Ancona, Italy i Division of Internal Medicine, Seconda Universit a degli Studi, Neaples, Italy j Department of Neuroscience, ‘Regina Elena’ Institute, Rome, Italy k Department of Oncology, S. Luigi Curr o Hospital, Catania, Italy l Division of Haematology, S. Francesco Hospital, Nuoro, Italy Received 25 November 2003; received in revised form 10 March 2004; accepted 11 March 2004 Available online 30 April 2004 Abstract Temozolomide is a well-tolerated alkylating agent, that is able to permeate the blood–brain barrier (BBB), and has additive cytotoxicity when given with radiotherapy (RT). A phase II trial assessing temozolomide 150 mg/m 2 /day, for 5 days every 28 days in primary central nervous system (CNS) lymphoma (PCNSL) patients with negative human immunodeficienct virus (HIV) serology, Eastern Cooperative Oncology Group (ECOG) performance status (PS)<4, previously treated with high-dose methotrexate- containing (HD-MTX) chemotherapy and/or RT was started. Twenty-three patients were enrolled. Median age was 60 years. Five complete remissions (median duration 6+ months; range 2–36 months), one partial response, four stable disease (median duration 7.2 months, range 2–16.5 months), and 13 progressions were observed. No major toxicities were observed, apart grade 3 vomiting in a single cycle. Main grade 1–2 toxicities were: 15% nausea, 6% vomiting, 9% fatigue and 9% neurological symptoms. This is the first prospective trial assessing single-agent activity in PCNSL at failure. Although some patients had a poor PS and had been heavily pre-treated, temozolomide yielded 26% objective responses and was well tolerated without any major toxicity. Ó 2004 Elsevier Ltd. All rights reserved. Keywords: Phase II trial; Primary CNS lymphoma; Salvage therapy; Temozolomide 1. Introduction Despite recent progress, results following treatment for primary central nervous system (CNS) lymphoma (PCNSL) patients remain disappointing, typically pro- ducing a 5-year survival rate of 22–40% [1–3]. Chemo- therapy followed by radiotherapy (RT) is the cornerstone of first-line treatment for PCNSL [4–7]. The principal drug in the management of PCNSL is high- dose methotrexate (HD-MTX), which yields 30–65% complete responses [8–10]. As no other single agent has been prospectively proven active against PCNSL, it is * Corresponding author. Tel.: +39-2-26437626; fax: +39-2-26437625. E-mail address: reni.michele@hsr.it (M. Reni). 0959-8049/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.ejca.2004.03.008 European Journal of Cancer 40 (2004) 1682–1688 www.ejconline.com European Journal of Cancer