title: Randomized phase II trial of carboplatin and paclitaxel with or without lonafarnib in first-line treatment of epithelial ovarian cancer stage IIB-IV.
abstract: OBJECTIVE
  This study evaluates whether a molecular targeted therapy with the farnesyltransferase inhibitor lonafarnib added to standard chemotherapy in first-line treatment of advanced ovarian cancer (OC) could improve progression-free (PFS) and overall survival (OS).
  
  
  METHODS
  We performed a prospective randomized phase II study to compare standard therapy carboplatin (C; AUC 5) and paclitaxel (T; 175 mg/m(2)) in primary advanced OC with or without lonafarnib (L). Lonafarnib was given in a dose of 100mg orally twice a day during chemotherapy and was increased afterwards to 200mg up to six months as a maintenance therapy.
  
  
  RESULTS
  105 patients were recruited (53 patients were randomized to receive LTC, 52 to TC). Hematologic toxicity was similar in both arms. Grade 3 and 4 non-hematological toxicity, occurred significantly more often with LTC (23% versus 4%, p=0.005) and was associated with a higher dropout rate. PFS and OS were not significantly different among both arms. The LTC arm showed inferiority in the stratum with residual tumor of more than 1cm: median PFS was 11.5 months (95% CI: 7.4-14.2) compared with 16.4 (95% CI: 10.3-40.4) for TC (p=0.0141; HR=0.36 (95% CI: 0.15-0.84)) with median OS 20.6 months (95% CI: 13.1-31.0) and 43.4 months (95% CI: 15.7-) for the TC arm (p=0.012; HR=0.32 (95% CI: 0.13-0.8)).
  
  
  CONCLUSIONS
  The addition of lonafarnib did not improve PFS or OS. Patients with a residual tumor of more than 1cm had significantly shorter PFS and OS. Incorporation of lonafarnib into future studies for primary therapy of OC is not recommended.
authors.affiliation: Department of Gynecology and Obstetrics, Evangelisches Krankenhaus Duesseldorf, Germany. wmeier1620@aol.com
authors.forename: Werner
authors.initials: W
authors.lastname: Meier
authors.forename: Andreas
authors.initials: A
authors.lastname: du Bois
authors.forename: Jörn
authors.initials: J
authors.lastname: Rau
authors.forename: Martina
authors.initials: M
authors.lastname: Gropp-Meier
authors.forename: Klaus
authors.initials: K
authors.lastname: Baumann
authors.forename: Jens
authors.initials: J
authors.lastname: Huober
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wollschlaeger
authors.forename: Rolf
authors.initials: R
authors.lastname: Kreienberg
authors.forename: Ulrich
authors.initials: U
authors.lastname: Canzler
authors.forename: Barbara
authors.initials: B
authors.lastname: Schmalfeldt
authors.forename: Pauline
authors.initials: P
authors.lastname: Wimberger
authors.forename: Barbara
authors.initials: B
authors.lastname: Richter
authors.forename: Willibald
authors.initials: W
authors.lastname: Schröder
authors.forename: Antje
authors.initials: A
authors.lastname: Belau
authors.forename: Anne
authors.initials: A
authors.lastname: Stähle
authors.forename: Alexander
authors.initials: A
authors.lastname: Burges
authors.forename: Jalid
authors.initials: J
authors.lastname: Sehouli
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 / Q000009:adverse effects; D000077216:Carcinoma, Ovarian Epithelial; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects; D011446:Prospective Studies; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects; D016019:Survival Analysis; D055815:Young Adult; D003986:Dibenzocycloheptenes
chemical_list: D016190:Carboplatin; D017239:Paclitaxel; D010880:Piperidines; D011725:Pyridines; C115354:lonafarnib; D003986:Dibenzocycloheptenes