title: Results of ZD0473 in platinum-pretreated ovarian cancer: analysis according to platinum free interval.
abstract: Resistance to platinum-containing regimens can develop in many women with ovarian cancer and may lead to relapse in > 80% of patients. ZD0473 is a new-generation platinum agent that, in preclinical studies, shows evidence of antitumour activity and overcomes platinum-resistance mechanisms. This Phase II trial has evaluated the efficacy and tolerability of ZD0473 in second-line ovarian cancer patients. Patients received ZD0473 120 mg/m2 (1-h iv infusion, day 1 q 3-weeks); the starting dose was increased to 150 mg/m2 after a safety review. We report here on results when patients are divided into four cohorts depending upon whether they were considered platinum-resistant or -sensitive. Patients were placed into one of 3 cohorts if they were platinum resistant (relapsed/progressed < or = 26 weeks after completion of prior platinum-based chemotherapy) or cohort 4 if this period was > 26 weeks (sensitive). Ninety-four patients were recruited to the trial (59 resistant, 35 sensitive; median age 58 [range 27-75] years; 86 with performance status [PS] < or = 1). Forty-nine patients received a starting dose of 120 mg/m2, of which 15 escalated to 150 mg/m2, and 45 received a starting dose of 150 mg/m2. Overall, the median number of treatment cycles received was 3 (range 1-8). Grade 3/4 thrombocytopenia was the most common haematological adverse event occurring in 62% of patients overall. Grade 3/4 lethargy, vomiting and nausea were the most common non-haematological toxicities. No clinically significant oto-, nephro- or neurotoxicity was observed. Overall response rates for all platinum-resistant and -sensitive patients were 8.3% and 32.4%, respectively. Stable disease occurred in 17 resistant and 15 sensitive 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 / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C110525:amminedichloro(2-methylpyridine)platinum(II)