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.


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 cyclophosphamide, doxorubicin, vincristine, dexamethasone/carmustine, vincristine, 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 <or=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.


CONCLUSIONS
The data presented show that the chemotherapy VIA is an effective salvage regimen for patients with recurrent PCNSL.
Arellano-Rodrigo
Eduardo
E
Service of Hematology, Institut de Recerca Biomèdica August Pi i Sunyer, Hospital Clínic, Barcelona, Spain.
López-Guillermo
Armando
A
Bessell
Eric M
EM
Nomdedeu
Benet
B
Montserrat
Emili
E
Graus
Francesc
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D002330:Carmustine / Q000008:administration & dosage; D002675:Child, Preschool; D017322:Clinical Trials, Phase II as Topic; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D004341:Drug Evaluation; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D015993:Life Tables; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000532:radiotherapy; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced; D012074:Remission Induction; D012189:Retrospective Studies; D016879:Salvage Therapy; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000139:chemically induced; D014750:Vincristine / Q000008:administration & dosage
D003561:Cytarabine; D014750:Vincristine; D005047:Etoposide; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D002330:Carmustine; D007069:Ifosfamide; D008727:Methotrexate