Clinical activity and benefit of irinotecan (CPT-11) in patients with colorectal cancer truly resistant to 5-fluorouracil (5-FU).
The aim of this prospective study was to assess the efficacy, clinical benefit and safety of CPT-11 (irinotecan) in patients with stringently-defined 5-fluorouracil-resistant metastatic colorectal cancer (CRC). 107 patients with documented progression of metastatic CRC during 5-FU were treated with CPT-11 350 mg/m2 once every 3 weeks in a multicentre phase II study. Tumour response and toxicity were assessed using WHO criteria. Changes in performance status (PS), weight and pain were also measured. The WHO response rate was 13/95 (13.7%, 95% CI 7.5% to 22.3%) eligible patients with a median duration of response of 8.5 months (37 weeks, range: 18-53+). There was also a high rate of disease stabilisation (44.2%) with a median duration of 4.8 months. The probability of being free of progression at 4 months was 50%. Median survival from first administration of CPT-11 was 10.4 months or 45 weeks (range: 3-66+ weeks). There was weight stabilisation or gain in 81% (73/90) of patients, a favourable outcome in PS in 91% (82/90) (improvement of WHO PS 2 or stabilisation of PS 0-1), and pain relief in 54% (26/48). There were no toxic deaths. Neutropenia was short-lasting and non-cumulative. Diarrhoea grade > or = 3 occurred in 7% of cycles and 28/107 (26%) of patients. CPT-11 350 mg/m2 once every 3 weeks has an encouraging degree of activity in progressive metastatic CRC truly resistant to 5-FU with a relatively high rate of tumour growth control translated into clinical benefit. The toxicity profile of CPT-11 is becoming better understood and has been considerably improved.
Van Cutsem
E
E
University Hospital Gasthuisberg, Department of Internal Medicine, Leuven, Belgium. eric.vancutsem@uz.kuleuven.ac.be
Cunningham
D
D
Ten Bokkel Huinink
W W
WW
Punt
C J
CJ
Alexopoulos
C G
CG
Dirix
L
L
Symann
M
M
Blijham
G H
GH
Cholet
P
P
Fillet
G
G
Van Groeningen
C
C
Vannetzel
J M
JM
Levi
F
F
Panagos
G
G
Unger
C
C
Wils
J
J
Cote
C
C
Blanc
C
C
Hérait
P
P
Bleiberg
H
H
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011788:Quality of Life; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin