دورية أكاديمية
A phase I and pharmacokinetic study of intraperitoneal topotecan
| العنوان: | A phase I and pharmacokinetic study of intraperitoneal topotecan |
|---|---|
| المؤلفون: | Hofstra, LS, de Vries, EGE, van der Zee, AGJ, Beijnen, JH, Rosing, H, Mulder, NH, Aalders, JG, Willemse, PHB |
| المصدر: | Hofstra , LS , de Vries , EGE , van der Zee , AGJ , Beijnen , JH , Rosing , H , Mulder , NH , Aalders , JG & Willemse , PHB 2001 , ' A phase I and pharmacokinetic study of intraperitoneal topotecan ' , British Jounal of Cancer , vol. 85 , no. 11 , pp. 1627-1633 . |
| سنة النشر: | 2001 |
| المجموعة: | University of Groningen research database |
| مصطلحات موضوعية: | intraperitoneal, topotecan, ovarian cancer, pharmacokinetics, phase I, EPITHELIAL OVARIAN-CANCER, CELL LUNG-CANCER, EVERY 21 DAYS, TOPOISOMERASE-I, INHIBITOR TOPOTECAN, CLINICAL-TRIALS, ACUTE-LEUKEMIA, CAMPTOTHECIN, DRUG, CHEMOTHERAPY |
| الوصف: | Purpose: To evaluate the feasibility and pharmacology of intraperitoneal (IP) topotecan. Patients and methods: Fifteen patients with recurrent ovarian cancer in a phase I trial were treated with escalating IP topotecan doses (5-30 mg/m(2)) for pharmacokinetic analysis. Results: Dose limiting toxicity (DLT) was acute hypotension, chills and fever at the 30 mg/m(2) dose level. Haematological toxicity and abdominal pain were mild for all dose levels studied. Pharmacokinetics: Peak plasma levels of total topotecan were reached at 2.7 +/- 1.1 h after IP instillation. The apparent V-SS was 69.9 +/- 25.4 L/m(2), plasma clearance 13.4 +/- 2.5 L/h/m(2) and plasma T1/2 3.7 +/- 1.3 h. The plasma AUC was correlated with the dose (R = 0.95, P <0.01). The plasma AUC ratio of lactone versus total topotecan (lactone + carboxy-forms) increased with the dose from 16% to 55%, (R = 0.84, P <0.01). Peritoneal total topotecan was cleared from the peritoneal cavity at 0.4 +/- 0.3 L/h.m(2) with a T1/2 = 2.7 +/- 1.7 h. The mean peritoneal/plasma AUC ratio for total topotecan was 54 - 34. Conclusion: A substantial dose of topotecan can be delivered by the IP route, achieving cytotoxic plasma levels of topotecan, with acceptable toxicity. The recommended dose for further phase 11 trials is 20 mg/m(2) IP, which enables combination with active doses of other cytotoxic drugs, in view of its limited myelotoxicity when given by this route. (C) 2001 Cancer Research Campaign. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://research.rug.nl/en/publications/0687adcf-dcb0-441d-8ceb-b1d1bcb83dbaTest |
| الإتاحة: | https://hdl.handle.net/11370/0687adcf-dcb0-441d-8ceb-b1d1bcb83dbaTest https://research.rug.nl/en/publications/0687adcf-dcb0-441d-8ceb-b1d1bcb83dbaTest https://pure.rug.nl/ws/files/62260347/A_phase_I_and_pharmacokinetic_study_of_intraperitoneal_topotecan.pdfTest |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.263B0743 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |