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.


METHODS
Between April 1995 and November 1996, 67 eligible patients with pretreated breast cancer (25 patients) and chemo-naïve colorectal (19 patients) and non-small-cell lung cancer (23 patients) were entered into three multicentric, non-randomized phase II trials. Treatment schedule consisted of intravenous GI1147211 administered at a dose of 1.2 mg/m2/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. Non-hematological toxicity was generally mild to moderate and consisted mainly of gastrointestinal toxicity, asthenia and alopecia. A dose-escalation to 1.5 mg/m2/d was feasible in 17 (25%) patients. The antitumor activity of GI1147211 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.
Gamucci
T
T
Division of Medical Oncology 1, Regina Elena Cancer Institute, Rome, Italy. mdb@crs.ifo.it
Paridaens
R
R
Heinrich
B
B
Schellens
J H
JH
Pavlidis
N
N
Verweij
J
J
Sessa
C
C
Kaye
S
S
Roelvink
M
M
Wanders
J
J
Hanauske
A
A
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D000970:Antineoplastic Agents; C091719:lurtotecan; D002166:Camptothecin