Phase I and pharmacokinetic study of trans-N3P3Az2(NHMe)4.
trans-N3P3Az2(NHMe)4, an aziridinyl-substituted cyclophosphazene, was tested for its toxicity, pharmacokinetic behavior, and cytostatic activity in a phase I study in 30 patients. A total of 66 courses of a single iv bolus injection were given in five dose steps. Toxicity consisted of leukocytopenia and thrombocytopenia, dose limiting at 70 mg/m2, mild anemia, and some nausea. Leukocyte and platelet count nadirs fell between 2 and 3 weeks, with recovery at 6 weeks. A tendency for cumulative thrombocytopenia was noticed in three of 13 patients at risk. A three-phase plasma elimination model was applicable with t1/2 alpha of 9.9 minutes, t1/2 beta of 78.5 minutes, and t1/2 gamma of 435.5 minutes; renal drug excretion was substantial. Three partial remissions in 21 evaluable patients suggest some clinical activity for this drug.
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents; D001388:Aziridines / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D001389:Azirines / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D004341:Drug Evaluation; D005260:Female; D006207:Half-Life; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy; D007700:Kinetics; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D008954:Models, Biological
D000970:Antineoplastic Agents; D001388:Aziridines; D001389:Azirines; C048802:1,3-diaziridino-2,4,6-triaza-1,3,5,5-tetraaminomethyl-1,3,5-triphosphorin