title: Paclitaxel/carboplatin with or without sorafenib in the first-line treatment of patients with stage III/IV epithelial ovarian cancer: a randomized phase II study of the Sarah Cannon Research Institute.
abstract: This trial compared the efficacy and toxicity of standard first-line treatment with paclitaxel/carboplatin versus paclitaxel/carboplatin plus sorafenib in patients with advanced ovarian carcinoma. Patients with stage 3 or 4 epithelial ovarian cancer with residual measurable disease or elevated CA-125 levels after maximal surgical cytoreduction were randomized (1:1) to receive treatment with paclitaxel (175 mg/m(2) , 3 h infusion, day 1) and carboplatin (AUC 6.0, IV, day 1) with or without sorafenib 400 mg orally twice daily (PO BID). Patients were reevaluated for response after completing 6 weeks of treatment (two cycles); responding or stable patients received six cycles of paclitaxel/carboplatin. Patients receiving the sorafenib-containing regimen continued sorafenib (400 PO BID) for a total of 52 weeks. Eighty-five patients were randomized and received treatment.Efficacy was similar for patients receiving paclitaxel/carboplatin/sorafenib versus paclitaxel/carboplatin: overall response rates 69% versus 74%; median progression-free survival 15.4 versus 16.3 months; 2 year survival 76% versus 81%. The addition of sorafenib added substantially to the toxicity of the regimen; rash, hand-foot syndrome, mucositis, and hypertension were significantly more common in patients treated with sorafenib. The addition of sorafenib to standard paclitaxel/carboplatin did not improve efficacy and substantially increased toxicity in the first-line treatment of advanced epithelial ovarian cancer. Based on evidence from this study and other completed trials, sorafenib is unlikely to have a role in the treatment of ovarian cancer.
authors.affiliation: Sarah Cannon Research Institute, Nashville, Tennessee.|Tennessee Oncology, PLLC, Nashville, Tennessee.
authors.forename: John D
authors.initials: JD
authors.lastname: Hainsworth
authors.affiliation: Sarah Cannon Research Institute, Nashville, Tennessee.|Tennessee Oncology, PLLC, Nashville, Tennessee.
authors.forename: Dana S
authors.initials: DS
authors.lastname: Thompson
authors.affiliation: Sarah Cannon Research Institute, Nashville, Tennessee.|Oncology Hematology Care, Cincinnati, Ohio.
authors.forename: John A
authors.initials: JA
authors.lastname: Bismayer
authors.affiliation: Sarah Cannon Research Institute, Nashville, Tennessee.|Tennessee Oncology, PLLC, Nashville, Tennessee.
authors.forename: Victor G
authors.initials: VG
authors.lastname: Gian
authors.affiliation: Sarah Cannon Research Institute, Nashville, Tennessee.|South Carolina Oncology Associates, Columbia, South Carolina.
authors.forename: William M
authors.initials: WM
authors.lastname: Merritt
authors.affiliation: Sarah Cannon Research Institute, Nashville, Tennessee.|Florida Cancer Specialists, Fort Myers, Florida.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Whorf
authors.affiliation: Sarah Cannon Research Institute, Nashville, Tennessee.
authors.forename: Lindsey H
authors.initials: LH
authors.lastname: Finney
authors.affiliation: Sarah Cannon Research Institute, Nashville, Tennessee.|Tennessee Oncology, PLLC, Nashville, Tennessee.
authors.forename: B Stephens
authors.initials: BS
authors.lastname: Dudley
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D017239:Paclitaxel / Q000008:administration & dosage; D010671:Phenylurea Compounds / Q000008:administration & dosage; D000077157:Sorafenib; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib; D016190:Carboplatin; D017239:Paclitaxel
keywords: Carboplatin; first-line therapy; ovarian cancer; paclitaxel; sorafenib