Phase I clinical and pharmacokinetic study of N 4 -behenoyl-1-β- d -arabinofuranosylcytosine

摘要: A phase I study ofN 4-behenoyl-1-β-d-arabinofuranosylcytosine (BHAC) was conducted in 66 patients, 41 with solid tumors and 25 hematological malignancies. The patients received either a 2-h single intravenous (i.v.) drip infusion (Schedule 1) or consecutive daily i.v. infusions 2). In Schedule 1 the dose initiated 1.5 mg kg−1 which escalated up to 7 kg−1. Side-effects were mild, included nausea, vomiting, epilation, hot flushes. Because of presence solvent vehicle, HCO-60 consideration mechanism action BHAC, escalation stopped at 2, started 8 given for 2–16 days. Myelosuppression found be dose-limiting toxicity. maximum tolerated (MTD) non-hematological assumed 5 × plasma disappearance curve BHAC looked biphasic, when 4 administered half-lives initial (t 1/2α) second 1/2β) calculated as 0.798 5.76 h respectively. 2 complete remission observed out 21 acute leukemia, one partial Hodgkin’s disease, 1-B response (Karnofsky) thyroid papillary adenocarcinoma.