T. Gamucci et al., Activity and toxicity of GI147211 in breast, colorectal and non-small-celllung cancer patients: An EORTC-ECSG phase II clinical study, ANN ONCOL, 11(7), 2000, pp. 793-797
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 pat
ients with pretreated breast cancer (25 patients) and chemo-naive colorecta
l (19 patients) and nonsmall-cell lung cancer (23 patients) were entered in
to three multicentric, non-randomized phase II trials. Treatment schedule c
onsisted 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 infecti
on in 14.5% of patients. Grade 3-4 thrombocytopenia and grade 2-4 anemia we
re observed in 20% and in 68% of patients, respectively. Nonhematological t
oxicity was generally mild to moderate and consisted mainly of gastrointest
inal toxicity, asthenia and alopecia. A dose-escalation to 1.5 mg/m(2)/d wa
s feasible in 17 (25%) patients. The antitumor activity of GI147211 was mod
erate 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, sho
wed an acceptable safety profile but a modest antitumor activity in the exa
mined tumor types.