Purpose: To determine the maximum tolerated dose and dose-limiting toxicities (DLTs) of ZD9331 in combination with cisplatin in patients with refractory solid tumors and to describe any preliminary antitumor activity associated with this regimen.
Materials and methods: Patients received combination therapy with ZD9331 as a 30-min infusion on days 1 and 8 of a 21-day cycle at doses of 100 or 130 mg/m(2), followed by cisplatin at 50 or 75 mg/m(2) as a 30- to 60-min infusion on day 1 only.
Results: A total of 16 patients received 59 cycles of ZD9331 and cisplatin. Patients were enrolled at three dose levels: ZD9331/cisplatin 100/50 ( n=3), 130/50 ( n=9), 130/75 ( n=4). DLTs at 130/75 included thrombocytopenia, neutropenia, fatigue, nausea, vomiting and stomatitis. Among 15 evaluable patients, 2 showed a partial response (patients with mesothelioma and head and neck cancer) and 6 showed stable disease (for a median of 5.5 cycles).
Conclusions: ZD9331 in combination with cisplatin was well tolerated at a dose of 130/50 mg/m(2) after establishing the principal DLTs of neutropenia and thrombocytopenia. The combination shows evidence of antitumor activity in a pretreated population.