Phase II trial of intracerebrospinal fluid etoposide in the treatment of neoplastic meningitis

Abstract

BACKGROUND The purpose of the current study was to determine the toxicity and response of a fixed dose intracerebrospinal fluid (CSF) etoposide in the treatment of patients with newly diagnosed neoplastic meningitis (NM). NM reportedly occurs in 1% to 5% of patients with known cancer. Currently available treatment options are limited and provide only modest benefit. METHODS Twenty‐seven patients (median age, 55 yrs) with clinically and cytologically documented NM received intra‐CSF etoposide. Tumor histologies included lung (8 patients), breast (5 patients), primary brain tumor (4 patients), non‐Hodgkin lymphoma (4 patients), melanoma (4 patients), colon (1 patient), and prostate (1 patient). Concurrent involved‐field radiotherapy (19 of 27 patients) or systemic chemotherapy (17 of 27 patients) was administered based on clinical indications. Etoposide was administered at a fixed dose (0.5 mg every day given 5 days per week every other week for 8 weeks [induction]). Patients were evaluated by CSF cytology and neurologic examination at the conclusion of induction therapy. Responding patients continued to receive etoposide (5 consecutive days every 4 weeks) with monthly evaluations. RESULTS Seven of 27 patients (26%) treated with etoposide had a cytologic response and either stable or improved neurologic status at the conclusion of induction. Eight patients (30%) developed disease progression during induction therapy and did not complete the 8‐week induction course of therapy. At the conclusion of induction therapy, 12 patients (44%) had persistently positive CSF cytology, although they were clinically stable. In responding patients, time to neurologic disease progression ranged from 8 weeks to 40 weeks (median, 20 wks). Toxicity manifested as transient chemical arachnoiditis (5 of 27 patients; 13% of all treatment cycles). The 6‐month neurologic disease progression‐free survival was 11%. CONCLUSIONS Etoposide appears to have modest activity against NM and easily managed toxicity. Cancer 2006. © 2006 American Cancer Society.