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 ≤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] ≤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 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.

Keywords:  Ovarian cancer, ZD0473, Monotherapy, Platinum resistance

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