A Phase II study of combined modality therapy of leptomeningeal metastases (LM) in melanoma was carried out. Central nervous system (CNS) metastases occur commonly in patients with clinically advanced melanoma. 16 patients (median age 47; range 32-62 years) with LM due to metastatic melanoma were treated. Neurologic presentation included: headache (9 patients); cranial neuropathies (6); cauda equina syndrome (4); gait ataxia (3); hemiparesis (2); radiculopathy (2); myelopathy (1); and seizure (1). All patients underwent CNS staging followed by radiotherapy (14 patients) and intraventricular chemotherapy (methotrexate 16 patients; ara-C 13 patients; thio-TEPA 7 patients). CNS imaging demonstrated: interrupted CSF flow (9 patients); parenchymal brain metastases (7); spinal cord subarachnoid nodules (5); hydrocephalus (3); and epidural spinal cord compression (2). CSF cytologic responses were seen in 4 patients to first-, 6 to second-, and 3 to third-line chemotherapy. Treatment-related toxicity included 13 patients with meningitis (12 chemical; 1 bacterial) and 12 patients (18 episodes) with myelosupression (4 episodes secondary to intraventricular chemotherapy). Median survival was 4 months (range: 2-8). Twelve patients (75%) died of progressive LM or combined LM and systemic disease progression. LM in patients with metastatic melanoma may be palliated with combined modality therapy, however, median survival is quite short suggesting a re-evaluation of such an approach in similarly affected patients.

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