A phase I and pharmacokinetic study of intraperitoneal topotecan
作者： L S Hofstra , A M E Bos , E G E de Vries , A G J van der Zee , J H Beijnen
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摘要: Purpose: To evaluate the feasibility and pharmacology of intraperitoneal (IP) topotecan. Patients methods: Fifteen patients with recurrent ovarian cancer in a phase I trial were treated escalating IP topotecan doses (5–30 mg/m2) for pharmacokinetic analysis. Results: Dose limiting toxicity (DLT) was acute hypotension, chills fever at 30 mg/m2 dose level. Haematological abdominal pain mild all levels studied. Pharmacokinetics: Peak plasma total reached 2.7 ± 1.1 h after instillation. The apparent V ss 69.9 25.4 L/m2, clearance 13.4 2.5 L/h/m2 T1/2 3.7 1.3 h. AUC correlated (R = 0.95, P < 0.01). ratio lactone versus (lactone + carboxy-forms) increased from 16% to 55%, 0.84, Peritoneal cleared peritoneal cavity 0.4 0.3 L/h.m2 1.7 h. mean peritoneal/plasma 54 34. Conclusion: A substantial can be delivered by route, achieving cytotoxic topotecan, acceptable toxicity. recommended further II trials is 20 mg/m2 IP, which enables combination active other drugs, view its limited myelotoxicity when given this route. © 2001 Cancer Research Campaign http://www.bjcancer.com
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