title: A phase II trial of ZD0473 in platinum-pretreated ovarian cancer.
abstract: The primary aim of this phase II trial was to assess the antitumour activity of ZD0473 in ovarian cancer patients who had failed initial platinum-based therapy. Patients (n=94) were classified as either platinum-sensitive (n=35) or platinum-resistant (n=59) depending on whether they had relapsed or progressed within 26 weeks of completing first-line platinum-based chemotherapy. Patients initially received 120 mg/m(2) ZD0473 as a 1-h intravenous (i.v.) infusion on day 1 of a 3-week cycle. If well tolerated, the dose could be escalated to 150 mg/m(2). Few patients (9%) withdrew because of treatment-related adverse events and no clinically significant oto-, nephro- or neurotoxicity was observed. Objective response rates for platinum-resistant and sensitive patients were 8.3 and 32.4%, respectively, and clinical benefit was observed in 76.5% of the sensitive patients. Median time to progression was 57 and 180 days, and median time to death was 242 and 402 days, for resistant and sensitive patients, respectively. In conclusion, ZD0473 has a manageable toxicity profile and encouraging activity in platinum-sensitive ovarian cancer patients.
authors.affiliation: Medical Oncology, Royal Marsden Hospital NHS Trust, London, UK. martin.gore@rmh.nthames.nhs.uk
authors.forename: M E
authors.initials: ME
authors.lastname: Gore
authors.forename: R J
authors.initials: RJ
authors.lastname: Atkinson
authors.forename: H
authors.initials: H
authors.lastname: Thomas
authors.forename: H
authors.initials: H
authors.lastname: Cure
authors.forename: D
authors.initials: D
authors.lastname: Rischin
authors.forename: P
authors.initials: P
authors.lastname: Beale
authors.forename: P
authors.initials: P
authors.lastname: Bougnoux
authors.forename: L
authors.initials: L
authors.lastname: Dirix
authors.forename: W M
authors.initials: WM
authors.lastname: Smit
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D019008:Drug Resistance, Neoplasm; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010984:Platinum / Q000627:therapeutic use; D017211:Treatment Failure; D014839:Vomiting / Q000139:chemically induced
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C110525:amminedichloro(2-methylpyridine)platinum(II); D010984:Platinum