Abstract
Cisplatin depletes MGMT and increases the sensitivity of leukemia cells to temozolomide. We performed a phase I study of cisplatin and temozolomide in patients with relapsed and refractory acute leukemia. Fifteen patients had AML, 3 had ALL, and 2 had biphenotypic leukemia. The median number of prior chemotherapy regimens was 3 (1–5). Treatment was well tolerated up to the maximal doses of temozolomide 200 mg/m2/d times 7 days and cisplatin 100 mg/m2 on day 1. There was one complete remission in this heavily pretreated patient population. Five of 20 (25%) patients demonstrated a significant reduction in bone marrow blasts.
Highlights
With currently available chemotherapy regimens, most patients with acute leukemia will not be cured[1,2]
Preclinical studies demonstrated that temozolomide is active against a broad range of tumor cell lines, including L1210 and P388 leukemia[3,4]
Patient Characteristics Twenty patients were treated on 4 dose levels of cisplatin plus temozolomide (Table 1)
Summary
With currently available chemotherapy regimens, most patients with acute leukemia will not be cured[1,2]. Temozolomide is a cytotoxic alkylating agent that is approved by the United States Food and Drug Administration for the treatment of patients with newly diagnosed glioblastoma multiforme as well adult patients with refractory anaplastic astrocytoma. Preclinical studies demonstrated that temozolomide is active against a broad range of tumor cell lines, including L1210 and P388 leukemia[3,4]. The recommended phase II dose of temozolomide was 200 mg/m2/d for 7 days. Two patients obtained formal complete remissions (CR), and 2 other patients had complete remission without platelet recovery (CRp). 5 other patients had significant decreases in bone marrow blasts despite not obtaining a formal response (total of 9 of 20 patients had a significant decrease in bone marrow blasts)
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