A Phase II Study of Temozolomide for Recurrent Brain Metastases.
Lauren E. Abrey, Jon D Olson, Dina Y Boutros, Michelle Mack, Ann Rodavitch, Jeffrey J Raizer, Mark G Malkin, Memorial Sloan-Kettering Cancer Ctr, New York, NY.

Treatment options for patients with recurrent brain metastases are extremely limited. Temozolomide is a new cytotoxic, alkylating agent that crosses the blood brain barrier and has preclinical evidence of efficacy across a wide range of solid tumors. Therefore, we conducted a phase II trial of temozolomide for patients with recurrent brain metastases. Eligible patients were treated with temozolomide 150mg/m2/day (200mg/m2/day, if no prior chemotherapy) for 5 days; treatment cycles were repeated every 28 days. The primary endpoint was radiographic response as assessed by gadolinium enhaced MRI scans using the MacDonald criteria. To date 36 pts (9 men, 27 women) with a median age of 60 (range:36-77) and a median KPS of 80 have been enrolled. Primary malignancies include: lung (58%), breast (25%), melanoma (8%), rectal(6%)and endometrial(3%) cancer. Grade 3 thrombocytopenia occurred in 2pts and grade 3/4 lymphopenia in 4pts. Significant non-hematologic toxicity included constipation and asymptomatic hepatic enzyme elevation. To date 26 patients have been evaluated for response: 2 partial response (8%), 9 stable disease (35%), and 15 progression. These preliminary results indicate that temozolomide is safe and well tolerated in this patient population. While radiographic response is uncommon more than one third of patients have stabilization of their progressive brain metastases. Time to progression and survival data are being analyzed.