Salvage treatment with etoposide (VP-16), ifosfamide and cytarabine (Ara-C) for patients with recurrent primary central nervous system lymphoma

Background: Survival of patients with primary central nervous system lymphoma (PCNSL) has improved with methotrexate-based combination regimens and radiotherapy (RT). However, the prognosis of patients who fail or relapse after initial response is poor. Very little data is available on salvage treatment at recurrence. Patients and methods: Sixteen immunocompetent patients (13 males/three females, median age 54 yr) with refractory (one patient) or recurrent (15 patients) PCNSL, homogeneously treated at diagnosis with the cyclophorphamide, doxorubicin, Vimcritime, dexamethasome/carmuntime, Uimcritime, cytarabine and methotrexate (CHOD/BVAM) "q3" and RT regimen, received etoposide (VP-16), ifosfamide and cytarabine (Ara-C) (VIA) chemotherapy as a salvage treatment. VIA included etoposide 100 mg/m(2)/d days 1-3, ifosfamide 1000 mg/m(2)/d days 1-5, and cytarabine 2000 mg/m(2)/12 h day 1. The therapy was repeated every 28 d for a total of planned six cycles. Results: Median time between first complete response (CR) and relapse was 19 months (range: 6-46 months). Thirteen patients (81%) had a performance status less than or equal to2, six had multifocal PCNSL and six (of eight tested) positive cerebrospinal fluid cytology. The median number of courses per patient was four (range: 1-6). Five patients completed the whole VIA therapy. Six patients (37%) achieved CR. After a median follow-up of 15 months for surviving patients, two have relapsed, with a median failure-free survival of 5 months. Twelve patients have died from progression of PCNSL, with a 12-month overall survival of 41% [95% confidence interval (CI): 16-66]. The major toxicity was World Health Organization grade 2-4 neutropenia (69% of patients) and thrombocytopenia (50%). Five patients had grade 3-4 infectious complications. Finally, one patient developed a severe but reversible ifosfamide encephalopathy. Conclusion: The data presented show that the chemotherapy VIA is an effective salvage regimen for patients with recurrent PCNSL.