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

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 (300%) 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.