P14.07 Multi-agent vs. single-agent intra-ventricular chemotherapy for patients with neoplastic meningitis: evidence supporting a new paradigm
Authors: R. Eby, B. Zacharia, L. Cream, D. Black, D. Aregawi, O. Mrowczynski, R. Strowd, S. Grossman, D. Claxton, M. Glantz
Journal: Neuro-Oncology (2017)

INTRODUCTION: Single-agent chemotherapy was abandoned decades ago in favor of multi-agent regimens for nearly all malignancies, but single-agent intraventricular chemotherapy remains the standard of care for patients with neoplastic meningitis (NM). In the five decades since Ommaya reservoirs became available, overall survival has remained dismal, and NM remains the most devastating and feared complication of cancer. METHODS: For the last five years, we have treated patients with NM with multi-agent intraventricular chemotherapy regimens tailored to the histology of the underlying cancer. From a list of 12 cytotoxic and targeted drugs which can safely be administered into the cerebrospinal fluid (CSF) we select the 4 most appropriate agents, and treat patients with two drugs at a time in alternating weekly cycles. We queried our multinational NM registry to identify patients with NM treated with this multi-agent regimen. We collected detailed demographic, treatment, and outcome data, and compared these characteristics with corresponding patient level data acquired from 6 of the 7 randomized controlled trials (RCTs) conducted in patients with NM, all of which used single-agent intraventricular therapies. RESULTS: Two-hundred and three patients with NM (139 with solid tumors, 44 with lymphoma, 20 with leukemia) were identified from our registry, and were compared to 300 patients from the RCTs (238 with solid tumors, 62 with lymphoma). RCT data for adults with leukemic meningitis are not available. Age, gender, KPS at the start of treatment, tumor histology, status of the primary cancer, and frequency of concurrent systemic chemotherapy or radiation did not differ between registry and RCT patients, or were less favorable in the registry patients. All patients from the registry patient group were included for analysis regardless of how many cycles of intraventricular therapy they received (intent-to-treat model). Median survival for the solid tumor, lymphoma, and leukemia groups (multi-agent vs. single-agent treatment) were 211 vs. 93.1 days (p<0.001), not reached (minimum of 266) vs. 81.2 days, and 205 days. Complete cytologic response rates were 33.3 vs. 23% (p=0.038), 59.3 vs. 25.8% (p=0.0027) and 70%. Frequency of death from solid tumor NM was 43.1% in the multi-agent vs. 57.5% in the single-agent therapy groups (p=0.0098). Frequencies of death from lymphomatous and leukemic NM were 29.2% and 23.5% (multi-agent therapy only; RCT data not available for this endpoint). Toxicity did not differ between the two treatment approaches. CONCLUSIONS: In patients with NM, multi-agent intraventricular chemotherapy appears to dramatically increase survival and frequency of complete responses, and markedly decrease the frequency of death from NM compared with single-agent therapy. These findings are biologically plausible, and merit additional study in the randomized trial setting.