PURPOSE: To estimate the maximum tolerated dose (MTD) of paclitaxel poliglumex (PPX) in combination with carboplatin in patients with chemotherapy-naive ovarian, primary peritoneal or fallopian tube cancer, and to assess the feasibility of administering multiple cycles of this regimen. METHODS: The first 11 patients were treated in a standard 3 + 3 dose-seeking design, with carboplatin held constant at area under the curve (AUC) of 6 and PPX at 225, 175 or 135 mg/m(2). Pharmacokinetics of PPX and carboplatin were evaluated during this dose-seeking component of the trial. MTD was defined by acute dose-limiting toxicities (DLT) in the first cycle. Twenty additional evaluable patients were treated at the estimated MTD to assess the feasibility of this regimen over >or=4cycles. RESULTS: PPX at 225 mg/m(2) resulted in DLT in 2/3 patients, and was de-escalated first to 175 mg/m(2) and then to 135 mg/m(2). PPX slowly hydrolyzed to paclitaxel and did not alter the pharmacokinetics of carboplatin. DLT within the first 4-cycles were observed in 3 patients (15%) treated at the MTD: neutropenia > 2weeks (2), febrile neutropenia (1). Nineteen patients (95%) experienced grade 4 neutropenia. Sixteen patients (80%) had at least one episode of grade 3 thrombocytopenia. Three patients (15%) had grade 2 and one had grade 3 peripheral neuropathy. Complete response by CA-125 was 75%. CONCLUSIONS: The recommended dose of PPX of 135 mg/m(2) with carboplatin (AUC = 6) in newly diagnosed ovarian cancer was feasible for multiple cycles, but hematologic toxicity was greater compared with standard carboplatin and 3-hour paclitaxel.
PURPOSE: To estimate the maximum tolerated dose (MTD) of paclitaxel poliglumex (PPX) in combination with carboplatin in patients with chemotherapy-naive ovarian, primary peritoneal or fallopian tube cancer, and to assess the feasibility of administering multiple cycles of this regimen. METHODS: The first 11 patients were treated in a standard 3 + 3 dose-seeking design, with carboplatin held constant at area under the curve (AUC) of 6 and PPX at 225, 175 or 135 mg/m(2). Pharmacokinetics of PPX and carboplatin were evaluated during this dose-seeking component of the trial. MTD was defined by acute dose-limiting toxicities (DLT) in the first cycle. Twenty additional evaluable patients were treated at the estimated MTD to assess the feasibility of this regimen over >or=4cycles. RESULTS:PPX at 225 mg/m(2) resulted in DLT in 2/3 patients, and was de-escalated first to 175 mg/m(2) and then to 135 mg/m(2). PPX slowly hydrolyzed to paclitaxel and did not alter the pharmacokinetics of carboplatin. DLT within the first 4-cycles were observed in 3 patients (15%) treated at the MTD: neutropenia > 2weeks (2), febrile neutropenia (1). Nineteen patients (95%) experienced grade 4 neutropenia. Sixteen patients (80%) had at least one episode of grade 3 thrombocytopenia. Three patients (15%) had grade 2 and one had grade 3 peripheral neuropathy. Complete response by CA-125 was 75%. CONCLUSIONS: The recommended dose of PPX of 135 mg/m(2) with carboplatin (AUC = 6) in newly diagnosed ovarian cancer was feasible for multiple cycles, but hematologic toxicity was greater compared with standard carboplatin and 3-hour paclitaxel.
Authors: Maria Luisa Veronese; Keith Flaherty; Amy Kramer; Barbara A Konkle; Mark Morgan; James P Stevenson; Peter J O'Dwyer Journal: Cancer Chemother Pharmacol Date: 2005-02-12 Impact factor: 3.333
Authors: Alan V Boddy; E Ruth Plummer; Radha Todd; Julieann Sludden; Melanie Griffin; Lesley Robson; James Cassidy; Donald Bissett; Alberto Bernareggi; Mark W Verrill; A Hilary Calvert Journal: Clin Cancer Res Date: 2005-11-01 Impact factor: 12.531
Authors: C P Belani; C M Kearns; E G Zuhowski; K Erkmen; D Hiponia; D Zacharski; C Engstrom; R K Ramanathan; M J Capozzoli; J Aisner; M J Egorin Journal: J Clin Oncol Date: 1999-02 Impact factor: 44.544
Authors: A du Bois; M Quinn; T Thigpen; J Vermorken; E Avall-Lundqvist; M Bookman; D Bowtell; M Brady; A Casado; A Cervantes; E Eisenhauer; M Friedlaender; K Fujiwara; S Grenman; J P Guastalla; P Harper; T Hogberg; S Kaye; H Kitchener; G Kristensen; R Mannel; W Meier; B Miller; J P Neijt; A Oza; R Ozols; M Parmar; S Pecorelli; J Pfisterer; A Poveda; D Provencher; E Pujade-Lauraine; M Randall; J Rochon; G Rustin; S Sagae; F Stehman; G Stuart; E Trimble; P Vasey; I Vergote; R Verheijen; U Wagner Journal: Ann Oncol Date: 2005 Impact factor: 32.976
Authors: C K Obasaju; S W Johnson; A Rogatko; D Kilpatrick; J M Brennan; T C Hamilton; R F Ozols; P J O'Dwyer; J M Gallo Journal: Clin Cancer Res Date: 1996-03 Impact factor: 12.531
Authors: Paul Sabbatini; Carol Aghajanian; Don Dizon; Sybil Anderson; Jakob Dupont; John V Brown; William A Peters; Andrew Jacobs; Aminder Mehdi; Saul Rivkin; Amy J Eisenfeld; David Spriggs Journal: J Clin Oncol Date: 2004-11-15 Impact factor: 44.544
Authors: Donald W Northfelt; Jacob B Allred; Heshan Liu; Timothy J Hobday; Mark W Rodacker; Alan P Lyss; Tom R Fitch; Edith A Perez Journal: Am J Clin Oncol Date: 2014-04 Impact factor: 2.339