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

• Published in: European journal of haematology Vol. 70; no. 4; pp. 219 - 224
• Main Authors: Arellano-Rodrigo, Eduardo, López-Guillermo, Armando, Bessell, Eric M., Nomdedeu, Benet, Montserrat, Emili, Graus, Francesc
• Format: Journal Article
• Language: English
• Published: Oxford, UK Munksgaard International Publishers 01.04.2003; Blackwell
• Subjects: Adolescent; Adult; Aged; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Brain Neoplasms - drug therapy; Brain Neoplasms - radiotherapy; Carmustine - administration & dosage; Chemotherapy; Child, Preschool; Clinical Trials, Phase II as Topic; Combined Modality Therapy; Cranial Irradiation; Cyclophosphamide - administration & dosage; Cytarabine - administration & dosage; Dexamethasone - administration & dosage; Disease-Free Survival; Doxorubicin - administration & dosage; Drug Evaluation; Etoposide - administration & dosage; Female; Humans; Ifosfamide - administration & dosage; Life Tables; Lymphoma, Non-Hodgkin - drug therapy; Lymphoma, Non-Hodgkin - radiotherapy; Male; Medical sciences; Methotrexate - administration & dosage; Middle Aged; Neoplasm Recurrence, Local - drug therapy; Neutropenia - chemically induced; Pharmacology. Drug treatments; primary CNS lymphoma; Remission Induction; Retrospective Studies; salvage chemotherapy; Salvage Therapy; Survival Analysis; Thrombocytopenia - chemically induced; VIA; Vincristine - administration & dosage; Antineoplastic agent; Central nervous system; Isomerases; Cytarabine; Lymphoproliferative syndrome; Primary; Malignant lymphoma; Antimitotic; Pyrimidine nucleoside; Human; DNA topoisomerase (ATP-hydrolysing); Drug combination; Enzyme; Ifosfamide; Etoposide; Enzyme inhibitor; Malignant hemopathy; Recurrent; VIA; Podophyllotoxine derivatives; Alkylating agent; Chemotherapy; Oxazaphosphinane derivatives; salvage chemotherapy; Treatment; Antimetabolic; Nitrogen mustard; primary CNS lymphoma
• ISSN: 0902-4441; 1600-0609
• DOI: 10.1034/j.1600-0609.2003.00045.x

:  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) and RT regimen, received etoposide (VP‐16), ifosfamide and cytarabine (Ara‐C) (VIA) chemotherapy as a salvage treatment. VIA included etoposide 100 mg/m2/d days 1–3, ifosfamide 1000 mg/m2/d days 1–5, and cytarabine 2000 mg/m2/12 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 ≤2, 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.