OBJECTIVE: The purpose of this study was to determine the efficacy, tolerability, and pharmacokinetics of intraperitoneal (ip) paclitaxel combined with intravenous (iv) carboplatin and cyclophosphamide. PATIENTS AND METHODS: Twenty-five newly diagnosed patients with Stage IC-IV epithelial ovarian cancer received ip paclitaxel with iv carboplatin and cyclophosphamide as a first-line treatment. Paclitaxel pharmacokinetics was determined during the first cycle on day 1 or 8. RESULTS: This regimen was well tolerated, as abdominal pain and hematological toxicities were minor, while neurotoxicity grade I/II was reported in only 20% and myalgia in 24% of patients and were fully reversible. After treatment 13 of 18 (72%) of the patients had no evidence of disease. At a median follow-up of 30 months patients with residual disease after surgery (n = 10) had a median progression-free survival (PSF) of 13 months; for the optimally debulked group (n = 15) the actuarial PFS was 60% at 48 months. The elimination of paclitaxel from the peritoneal cavity and plasma followed first-order kinetics and was not influenced by adding carboplatin with cyclophosphamide. CONCLUSION: This regimen was well tolerated, with minimal hematologic or neurotoxicity, and allowed the application of a triple-drug schedule without compromising dose intensity. To judge its efficacy, comparison with a standard iv paclitaxel-based schedule should be performed in a formal phase III study.
OBJECTIVE: The purpose of this study was to determine the efficacy, tolerability, and pharmacokinetics of intraperitoneal (ip) paclitaxel combined with intravenous (iv) carboplatin and cyclophosphamide. PATIENTS AND METHODS: Twenty-five newly diagnosed patients with Stage IC-IV epithelial ovarian cancer received ip paclitaxel with iv carboplatin and cyclophosphamide as a first-line treatment. Paclitaxel pharmacokinetics was determined during the first cycle on day 1 or 8. RESULTS: This regimen was well tolerated, as abdominal pain and hematological toxicities were minor, while neurotoxicity grade I/II was reported in only 20% and myalgia in 24% of patients and were fully reversible. After treatment 13 of 18 (72%) of the patients had no evidence of disease. At a median follow-up of 30 months patients with residual disease after surgery (n = 10) had a median progression-free survival (PSF) of 13 months; for the optimally debulked group (n = 15) the actuarial PFS was 60% at 48 months. The elimination of paclitaxel from the peritoneal cavity and plasma followed first-order kinetics and was not influenced by adding carboplatin with cyclophosphamide. CONCLUSION: This regimen was well tolerated, with minimal hematologic or neurotoxicity, and allowed the application of a triple-drug schedule without compromising dose intensity. To judge its efficacy, comparison with a standard iv paclitaxel-based schedule should be performed in a formal phase III study.
Authors: Stephen K Williamson; Gary A Johnson; Holly A Maulhardt; Kathleen M Moore; D S McMeekin; Thomas K Schulz; Gregory A Reed; Katherine F Roby; Christine B Mackay; Holly J Smith; Scott J Weir; Jo A Wick; Maurie Markman; Gere S diZerega; Michael J Baltezor; Jahna Espinosa; Charles J Decedue Journal: Cancer Chemother Pharmacol Date: 2015-04-23 Impact factor: 3.333
Authors: Mihaela C Cristea; Paul Frankel; Timothy Synold; Saul Rivkin; Dean Lim; Vincent Chung; Joseph Chao; Mark Wakabayashi; Benjamin Paz; Ernest Han; Paul Lin; Lucille Leong; Amy Hakim; Mary Carroll; Neal Prakash; Thanh Dellinger; Min Park; Robert J Morgan Journal: Cancer Chemother Pharmacol Date: 2019-01-08 Impact factor: 3.333