title: Phase II study of carboplatin followed by sequential gemcitabine and paclitaxel as first-line treatment for advanced ovarian cancer.
abstract: The aim of this exploratory phase II study was to evaluate sequential chemotherapy with carboplatin followed by gemcitabine-paclitaxel combination in chemonaive patients with advanced ovarian cancer. The primary objective was to evaluate time to progressive disease (TTPD); secondary objectives included the evaluation of 1- and 3-year survival, response rates, and toxicity. Following initial debulking surgery or biopsy, patients with FIGO stage IIC-IV disease received four cycles of carboplatin area under the curve (AUC) 6 (day 1) every 21 days, followed by four cycles of gemcitabine 1000 mg/m(2) (days 1 and 8) and paclitaxel 175 mg/m(2) (day 8) every 21 days. A total of 47 patients enrolled, 44 (93.6%) completed the initial four cycles, and 39 patients (82.9%) completed the planned eight cycles. The median and maximum lengths of follow-up were 31.2 and 43.7 months, respectively. Median TTPD was 13.8 months (95% CI, 11.6-21.0 months), and median survival time was 31.2 months (95% CI, 25.2-39.6 months). Survival at 1 and 3 years was 95.7% and 44.2%, respectively. Of the 43 evaluable patients, most (95.3%) of them achieved a CA-125 marker response based on Gynecologic Cancer Intergroup (GCIG) definition. The partial response rate in the seven patients with measurable disease was 46.4%. Myelosuppression was the major toxicity, with grade 3 and 4 neutropenia observed in 76.6% patients and thrombocytopenia in 12.8% patients. The sequential approach of carboplatin followed by gemcitabine-paclitaxel as first-line treatment for patients with ovarian cancer is feasible and well tolerated, and depending upon the findings from other major trials, it may merit further evaluation.
authors.affiliation: Prince of Wales Hospital, Randwick, New South Wales, Australia. Michael.Friedlander@sesiahs.health.nsw.gov.au
authors.forename: M
authors.initials: M
authors.lastname: Friedlander
authors.forename: M
authors.initials: M
authors.lastname: Buck
authors.forename: D
authors.initials: D
authors.lastname: Wyld
authors.forename: M
authors.initials: M
authors.lastname: Findlay
authors.forename: B
authors.initials: B
authors.lastname: Fitzharris
authors.forename: P
authors.initials: P
authors.lastname: De Souza
authors.forename: T
authors.initials: T
authors.lastname: Davies
authors.forename: G
authors.initials: G
authors.lastname: Kalimi
authors.forename: S
authors.initials: S
authors.lastname: Allan
authors.forename: D
authors.initials: D
authors.lastname: Perez
authors.forename: P
authors.initials: P
authors.lastname: Harnett
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002277:Carcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D016019:Survival Analysis; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D016190:Carboplatin; D017239:Paclitaxel; D000093542:Gemcitabine