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A phase I dose-finding study of a combination of pegylated liposomal doxorubicin (Doxil), carboplatin and paclitaxel in ovarian cancer

Standard chemotherapy for advanced epithelial ovarian cancer is a combination of platinum-paclitaxel. One strategy to improve the outcome for patients is to add other agents to standard therapy. Doxil is active in relapsed disease and has a response rate of 25% in platinum-resistant relapsed disease...

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Detalles Bibliográficos
Autores principales: Gibbs, D D, Pyle, L, Allen, M, Vaughan, M, Webb, A, Johnston, S R D, Gore, M E
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2002
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2375380/
https://www.ncbi.nlm.nih.gov/pubmed/11986767
http://dx.doi.org/10.1038/sj.bjc.6600250
Descripción
Sumario:Standard chemotherapy for advanced epithelial ovarian cancer is a combination of platinum-paclitaxel. One strategy to improve the outcome for patients is to add other agents to standard therapy. Doxil is active in relapsed disease and has a response rate of 25% in platinum-resistant relapsed disease. A dose finding study of doxil-carboplatin-paclitaxel was therefore undertaken in women receiving first-line therapy. Thirty-one women with epithelial ovarian cancer or mixed Mullerian tumours of the ovary were enrolled. The doses of carboplatin, paclitaxel and doxil were as follows: carboplatin AUC 5 and 6; paclitaxel, 135 and 175 mg m(−2); doxil 20, 30, 40 and 50 mg m(−2). Schedules examined included treatment cycles of 21 and 28 days, and an alternating schedule of carboplatin-paclitaxel (q 21) with doxil being administered every other course (q 42). The dose-limiting toxicities were found to be neutropenia, stomatitis and palmar plantar syndrome and the maximum tolerated dose was defined as; carboplatin AUC 5, paclitaxel 175 mg m(−2) and doxil 30 mg m(−2) q 21. Reducing the paclitaxel dose to 135 mg m(−2) did not allow the doxil dose to be increased. Delivering doxil on alternate cycles at doses of 40 and 50 mg m(−2) also resulted in dose-limiting toxicities. The recommended doses for phase II/III trials are carboplatin AUC 6, paclitaxel 175 mg m(−2), doxil 30 mg m(−2) q 28 or carboplatin AUC 5, paclitaxel 175 mg m(−2), doxil 20 mg m(−2) q 21. Grade 3/4 haematologic toxicity was common at the recommended phase II doses but was short lived and not clinically important and non-haematologic toxicities were generally mild and consisted of nausea, paraesthesiae, stomatitis and palmar plantar syndrome. British Journal of Cancer (2002) 86, 1379–1384. DOI: 10.1038/sj/bjc/6600250 www.bjcancer.com © 2002 Cancer Research UK