VSE knjižnice (vzajemna bibliografsko-kataložna baza podatkov COBIB.SI)
  • Phase I and pharmacokinetic study of intraperitoneal topotecan
    Plaxe, SC ...
    Objective: To determine the maximum tolerated dose and pharmacokinetics of topotecan when administered by the intraperitoneal route. Methods: A dose-escalating Phase I trial was conducted in which ... fifteen % of the total dose was given as an intraperitoneal bolus in two litres of D5W and the remainder was given as a continuous intraperitoneal infusion over 24 hours. Treatments were given every 21 days. Pharmacokinetic analyses were performed at the recommended phase II dose. Results: Seventeen patients received a totalof 43 cycles at 21-day intervals. The maximum tolerated dose was 4 mg/m2 and acute dose-limiting toxicity was neutropenia. Other toxicities included leukopenia, anemia, emesis, fever, and abdominal pain. Although no objective responses were achieved, five of ten patients with ascites had a decrease in fluid accumulation with administration of intraperitoneal topotecan. The recommended phase II dose is 3 mg/m2. Pharmacokinetic analysis performed at a dose of 3 mg/m2 demonstrated that elimination from the peritoneal cavity followed second-order kinetics with k1 = 1.6 hr(-1), k2 = 0.3 hr(-1) and firstand second-phase half-lives of 0.49 and 2.7 hours, respectively. Plasma pharmacokinetic behavior was best described by first-order kinetics with k = 0.5 hr(-1) and a half-life of 3.9 hours. The pharmacologic advantage, expressed as the peritoneal to plasma AUC ratio was 31.2. Conclusion: Intraperitoneal administration of topotecan at 3 mg/m2 results in a substantial increase in drug exposure for the peritoneal cavity without compromising systemic exposure; this may be beneficial for the treatment of patients with ovarian cancer or intraperitoneal carcinomatosis.
    Vir: Investigational new drugs. - ISSN 0167-6997 (Letn. 16, št. 2, 1998, str. 147-153)
    Vrsta gradiva - članek, sestavni del
    Leto - 1998
    Jezik - angleški
    COBISS.SI-ID - 16507865

vir: Investigational new drugs. - ISSN 0167-6997 (Letn. 16, št. 2, 1998, str. 147-153)
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