A phase I-II study of combination therapy with thymidine and cytosine arabinoside

Twenty-one patients with leukemia and lymphoma refractory to conventional therapy were treated with thymidine (dThd) at a dose of 75 g/m2/day for 48 h by continuous intravenous (IV) infusion, followed by cytosine arabinoside (ara-C) on an escalating dose schedule of 25-625 mg/m2/day for 48 h by continuous IV infusion. Toxicity included somnolence (1 patient), mucositis (2 patients), and myelosuppression (19 patients). One patient died prior to completion of therapy. Because of the patient population studied (mainly consisting of patients with leukemia refractory to conventional therapy) and the prevalence of myelosuppression prior to therapy, a median toxic dose was not evaluable. Therapeutic responses included a partial remission in a patient with acute myelogenous leukemia (AML) refractory to ara-C. An additional six patients with acute leukemia refractory to ara-C transiently cleared their peripheral blood of blasts, and a decrease in circulating blasts was noted in two other patients. Biochemical studies conducted on the peripheral blasts of two patients confirmed an enhancement by dThd of the incorporation of ara-C into the DNA of circulating blasts.