Whole-brain radiotherapy (WBRT) and high-dose methylprednisolone (HDMP) for elderly patients with primary central nervous system lymphoma (PCNSL): Results of North Central Cancer Treatment Group (NCCTG) 96-72-51

Abstract

PCNSL targets especially vulnerable populations, and is invariably lethal without treatment. Current treatments are extending survival but are not increasing the number of cured patients. Furthermore the quality of such survival is poor. Elderly PCNSL patients are especially susceptible to neurotoxicity. NCCTG 967351 was designed to evaluate the efficacy, toxicity, and survival of WBRT and HDMP in newly diagnosed PCNSL patients 70 years of age and older. HDMP was chosen because it has cytotoxic activity against lymphoma cell lines, may decrease toxicity by direct and indirect modulation of excitatory CNS cytokines, and effectively closes the blood-brain barrier for 30 days. Immune-competent patients 70 years and older with PCNSL and without evidence of systemic disease were eligible. Patients received 1gm of methylprednisolone once-daily for 5 days starting 30 days after completing radiotherapy (WBRT 4140 cGy/23 fractions with 900cGy boost to contrast-enhancing disease). Patients then received 1 gm of methylprednisolone every 28 days until progression. Primary endpoint was overall survival (OS) at 6 months. A planned interim analysis was performed after the 12th eligible patient was followed for six months. Survival results were compared to age-matched patients on the previous phase-II NCCTG trial 86-72-52, in which patients received pre-WBRT cytoxan, adriamycin, vincristine, prednisone (CHOP) and consolidative high-dose Ara-C. The current regimen would be considered inactive if 6-month survival was shorter than that of patients treated with CHOP-RT. 19 patients were accrued between 1998 and 2003. Median age of patients was 76 years (range 70–83). Median ECOG performance status was 1.5. Interim analysis revealed a 6-month survival of 33%. By the protocol-decision rule, the regimen was considered inactive and the trial closed. No differences in OS, progression-free survival (PFS), or toxicity between age-matched patients on the current study when compared to those receiving pre-WBRT CHOP/Ara-C on NCCTG 86-72-52. In the group of patients who survived 30 days after WBRT (n = 10) and thus received HDMP, patients who received HDMP appeared to have longer OS (14.3 mos v. 6.5 mos, p = 0.54) and PFS (14.3 mos v. 3.1 mos, p = 0.032) compared to the ten NCCTG 86-72-52 patients alive 30 days after WBRT. Patients surviving 30 days after WBRT who received HDMP had prolongation of OS and PFS compared to patients receiving pre-WBRT CHOP/Ara-C. The numbers of patients are too small for statistical conclusions. However, given that the comparison cohort from NCCTG 86-72-52 had received WBRT and chemotherapy, the HDMP regimen deserves further study. A replacement study utilizing HDMP at WBRT initiation is under review