Yoshi 864 (NSC 102627) 1-propanol, 3, 3'-iminodi-dimethanesulfonate (ester) hydrochloride: a phase 1 study.
Yoshi 864 was given i.v. push daily times 5 with 6 weeks' followup. Dose escalation was from 0.25 mg/kg to 2.7 mg/kg. Toxicity and effectiveness were first seen at 1.5 mg/kg. Twenty-five courses were given to 16 patients at or above this level. In 16 of 22 courses, exclusive of CML, thrombopenia and/or leukopenia occurred. Mean platelet and WBC nadirs occurred on day 24 and 29 with recovery taking 1-2 weeks and 2-3 weeks respectively. Hb fell in 11 courses. At 2.7 mg/kg, nausea and vomiting lasting 6-12 days occurred in 3 of 7 courses; during 5 coures patients slept 20 hours a day, and 1 was comatose for 2 days. Two patients with squamous cell carcinoma and 1 with an unknown primary responded. Both patients with CML had clinical remissions. It is recommended that a cooperative Phase II Study in a broad spectrum of human solid tumors including lymphomas and chronic myelocytic leukemia be undertaken at a dose level of 2 mg/kg.
D000477:Alkylating Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D003128:Coma / Q000139:chemically induced; D005500:Follow-Up Studies; D006801:Humans; D008698:Mesylates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009290:Narcolepsy / Q000139:chemically induced; D009369:Neoplasms / Q000188:drug therapy*; D011437:Propylamines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012075:Remission, Spontaneous
D000477:Alkylating Agents; D008698:Mesylates; D011437:Propylamines