title: Open-label feasibility study of pazopanib, carboplatin, and paclitaxel in women with newly diagnosed, untreated, gynaecologic tumours: a phase I/II trial of the AGO study group.
abstract: BACKGROUND
  Although most patients with advanced gynaecologic malignancies respond to first-line treatment with platinum-taxane doublets, a significant proportion of patients relapse. Combining targeted agents that have non-overlapping mechanisms of action with chemotherapy may potentially increase the disease-free interval. Accordingly, this study evaluated the feasibility of combining pazopanib, an oral angiogenesis inhibitor, with paclitaxel and carboplatin.
  
  
  METHODS
  This open-label, phase I/II study planned to evaluate the safety and efficacy of paclitaxel 175 mg m(-2) plus carboplatin (AUC5 (Arm A) or AUC6 (Arm B)) once in every 3 weeks for up to six cycles with either 800 or 400 mg per day pazopanib.
  
  
  RESULTS
  Dose-limiting toxicities (DLTs) were observed in two of the first six patients enrolled at pazopanib 800 mg plus paclitaxel 175 mg m(-2) plus carboplatin AUC5. Of the six patients enrolled in the next and lowest dosing level planned in the study, pazopanib 400 mg plus paclitaxel 175 mg m(-2) plus carboplatin AUC5, two patients also experienced DLTs and the study was terminated. Two of the 4 DLTs observed overall were gastrointestinal perforations. Severe myelotoxicity was reported in 6 of 12 patients.
  
  
  CONCLUSIONS
  Combining either 800 or 400 mg per day pazopanib with standard carboplatin/paclitaxel chemotherapy is not a feasible treatment option.
authors.affiliation: Departments of Gynecology and Gynecologic Oncology, Kliniken Essen Mitte, Henricistrasse 92, 45136 Essen, Germany. prof.dubois@googlemail.com
authors.forename: A
authors.initials: A
authors.lastname: du Bois
authors.forename: I
authors.initials: I
authors.lastname: Vergote
authors.forename: P
authors.initials: P
authors.lastname: Wimberger
authors.forename: I
authors.initials: I
authors.lastname: Ray-Coquard
authors.forename: P
authors.initials: P
authors.lastname: Harter
authors.forename: L B
authors.initials: LB
authors.lastname: Curtis
authors.forename: I
authors.initials: I
authors.lastname: Mitrica
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D057239:Early Termination of Clinical Trials; D005240:Feasibility Studies; D005260:Female; D005833:Genital Neoplasms, Female / Q000188:drug therapy*; D006801:Humans; D007191:Indazoles; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage; D013449:Sulfonamides / Q000008:administration & dosage
chemical_list: D007191:Indazoles; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib; D016190:Carboplatin; D017239:Paclitaxel