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.
D000447:Aldehydes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001855:Bone Marrow Diseases / Q000139:chemically induced; D002118:Calcium / Q000378:metabolism; D002986:Clinical Trials as Topic; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007263:Infusions, Parenteral; D007288:Inosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007674:Kidney Diseases / Q000139:chemically induced; D009369:Neoplasms / Q000188:drug therapy*; D013997:Time Factors
D000447:Aldehydes; D000970:Antineoplastic Agents; D007288:Inosine; D002118:Calcium