Systemic and intraventricular chemotherapy with deferred radiotherapy for primary central nervous system lymphoma (PCNSL): final report of a pilot and phase II study

Purpose: To evaluate response rate, response duration, overall survival, and toxicity in PCNSL after systemic and intraventricular chemotherapy with deferred radiotherapy.

Patients and Methods: From 09/1995 to 04/2002, 88 consecutive patients with PCNSL (median age 62 years) were enrolled in a pilot/phase II study evaluating high-dose methotrexate (MTX) (cycles 1,2,4,5) and cytarabine (ara-C) (cycles 3,6) based systemic therapy (including dexamethasone, vinca-alkaloids, ifosfamide and cyclophosphamide) combined with intraventricular MTX, prednisolone and ara-C.

Results: Seventy-three of 88 patients were evaluable for response. (Seven were lost for follow up, 4 had no detectable tumor prior to therapy and 4 terminated therapy prematurely). Seven (8%) out of 88 patients died due to treatment-related complications. From a total of 80 patients (7 with early death and 73 evaluable for response) 47 (59%) achieved complete response (CR), 11 (14%) partial response (PR), and 15 (19%) progressed despite therapy. Follow-up is 0 to 99 months (median 50). Kaplan Meier estimate for median time to treatment failure (TTF) is 21 and for median overall survival 55 months. In patients younger than 60 years neither median survival nor median TTF has yet been reached. No treatment related late neurotoxicity occurred. MRI carried out after the second cycle was highly predictive of long-term prognosis: Only 2/18 patients with CR, but all out of 47 patients with PR or stable disease (SD) after two cycles experienced treatment failure during follow up (p< .0001).

Conclusions: Polychemotherapy based on high-dose MTX and ara-C is highly efficient in PCNSL. Neurotoxicity was infrequent in this series. Early CR is highly prognostic and calls for risk-stratified strategies.