Activity and toxicity of GI147211 in breast, colorectal and non-small-cell lung cancer patients: An EORTC-ECSG phase II clinical study

Background: GI147211 is a water-soluble synthetic analogue of camptothecin showing promising in vivo and in vitro antitumor activity and an acceptable toxicity profile. Patients and methods: Between April 1995 and November 1996, 67 eligible patients with pretreated breast cancer (25 patients) and chemo-naive colorectal (19 patients) and nonsmall-cell lung cancer (23 patients) were entered into three multicentric, non-randomized phase II trials. Treatment schedule consisted of intravenous GI147211 administered at a dose of 1.2 mg/m(2)/day for five consecutive days every three weeks. Results: Hematological toxicity was common with grade 3-4 neutropenia in 54% of patients and neutropenic fever together or not associated with infection in 14.5% of patients. Grade 3-4 thrombocytopenia and grade 2-4 anemia were observed in 20% and in 68% of patients, respectively. Nonhematological toxicity was generally mild to moderate and consisted mainly of gastrointestinal toxicity, asthenia and alopecia. A dose-escalation to 1.5 mg/m(2)/d was feasible in 17 (25%) patients. The antitumor activity of GI147211 was moderate in breast cancer patients (3 partial responses (PRs), response rate (RR) 13%) and minimal in non-small cell lung cancer patients (2 PRs, RR 9%). No objective responses were obtained in colorectal patients. Conclusions: GI147211, at the dose and schedule employed in this study, showed an acceptable safety profile but a modest antitumor activity in the examined tumor types.