Clinical phase I trial of inosine dialdehyde (NSC-118994).

An initial clinical phase I trial of inosine dialdehyde has been carried out in 40 patients at dose levels of 30-4000 mg/m2 for 5 days given intravenously (iv) monthly. At 1.5 g/m2, noncumulative dose-related toxicity occurred in all patients which consisted of nausea and vomiting, local pain, alterations in coagulation mechanism, elevated partial thromboplastin time, and positive Coombs' test. No dose-limiting leukopenia, thrombocytopenia, anemia, or bleeding occurred; however, depression of the leukocyte and platelet counts, and decreased hemoglobin value were observed. The dose-limiting toxic effect was renal tubular damage with reversible acute renal failure in one of four patients who received 3000 mg/m2 iv for 5 days. Refractory hypercalcemia was controlled in three of three patients without tumor effect. Responses occurred in patients with seminoma, oat cell carcinoma, and melanoma. A starting dose of 2 g/m2 for 3 days monthly is recommended for phase II trials and a trial in lung carcinoma is now being conducted.