Phase I clinical trial of isophosphamide (NSC-109724).
An initial clinical phase I trial of isophosphamide has been carried out at dose levels of 200-10,000 mg/m2 of body surface area using a single-dose, every-3-week schedule. Significant toxicity was not seen at isophosphamide dose levels less than 2900 mg/m2. At higher doses, nausea and vomiting was nearly universal. Hematologic toxicity manifested by leukopenia occurred in 12 of 20 patients treated with doses of 3800-7000 mg/m2. Thrombocytopenia to 100,000 platelets/mm3 was not seen in any patient. Urinary bladder toxicity manifested by hemorrhagic cystitis was seen in 15 of 23 patients treated with doses of 3800-10,000 mg/m2. Hemorrhagic cystitis could be completely prevented by bladder irrigation with N-acetyl-L-cysteine (1% solution, 2000 ml/day). With careful attention to hydration, renal toxicity was largely prevented with blood urea nitrogen elevations to 30 mg/dl in only two of 14 patients receiving isophosphamide doses of 5000-7000 mg/m2. Another side effect was central nervous system toxicity in seven of 17 patients at doses of 5000-10,000 mg/m2. For phase II trials a dose of 5000 mg/m2 is recommended, with careful attention to the state of hydration in the patient and with the knowledge that bladder irrigation may be necessary for the prevention and/or amelioration of bladder toxicity.
D000230:Adenocarcinoma / Q000188:drug therapy; D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D002986:Clinical Trials as Topic; D003520:Cyclophosphamide / Q000031:analogs & derivatives*; D004341:Drug Evaluation; D006801:Humans; D007069:Ifosfamide / Q000009:adverse effects / Q000627:therapeutic use*; D007671:Kidney Concentrating Ability; D007684:Kidney Tubules / Q000503:physiopathology; D007970:Leukopenia / Q000139:chemically induced; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D013921:Thrombocytopenia / Q000139:chemically induced; D001745:Urinary Bladder Diseases / Q000139:chemically induced
D003520:Cyclophosphamide; D007069:Ifosfamide