Phase I and pharmacokinetic study of intraperitoneal topotecan.

摘要: Objective. To determine the maximum tolerated dose and pharmacokinetics of topotecan when administered by intraperitoneal route. Methods. A dose-escalating Phase I trial was conducted in which fifteen % total given as an bolus two litres D5W remainder a continuous infusion over 24 hours. Treatments were every 21 days. Pharmacokinetic analyses performed at recommended phase II dose. Results. Seventeen patients received 43 cycles 21-day intervals. The 4 mg/m2 acute dose-limiting toxicity neutropenia. Other toxicities included leukopenia, anemia, emesis, fever, abdominal pain. Although no objective responses achieved, five ten with ascites had decrease fluid accumulation administration topotecan. is 3 mg/m2. analysis demonstrated that elimination from peritoneal cavity followed second-order kinetics k1 = 1.6 hr-1, k2 0.3 hr-1 first second-phase half-lives 0.49 2.7 hours, respectively. Plasma pharmacokinetic behavior best described first-order k 0.5 half-life 3.9 pharmacologic advantage, expressed to plasma AUC ratio 31.2. Conclusions. Intraperitoneal results substantial increase drug exposure for without compromising systemic exposure; this may be beneficial treatment ovarian cancer or carcinomatosis.