Clinical activity and benefit of irinotecan (CPT-11) in patients with colorectal cancer truly resistant to 5-fluorouracil (5-FU)

• Published in: European journal of cancer (1990) Vol. 35; no. 1; pp. 54 - 59
• Main Authors: Van Cutsem, E, Cunningham, D, Ten Bokkel Huinink, W.W, Punt, C.J.A, Alexopoulos, C.G, Dirix, L, Symann, M, Blijham, G.H, Cholet, P, Fillet, G, Van Groeningen, C, Vannetzel, J.M, Levi, F, Panagos, G, Unger, C, Wils, J, Cote, C, Blanc, C, Hérait, P, Bleiberg, H
• Format: Journal Article Web Resource
• Language: English
• Published: Oxford Elsevier Ltd 01.01.1999; Elsevier; Elsevier Science
• Subjects: 5-FU resistant; Adult; Aged; Antimetabolites, Antineoplastic - therapeutic use; Antineoplastic agents; Antineoplastic Agents, Phytogenic - therapeutic use; Biological and medical sciences; Camptothecin - analogs & derivatives; Camptothecin - therapeutic use; Chemotherapy; colon cancer; Colorectal Neoplasms - drug therapy; CPT-11; Drug Resistance, Neoplasm; Female; Fluorouracil - therapeutic use; Hematologic Diseases - chemically induced; Hematology; Human health sciences; Humans; Hématologie; Irinotecan; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Prospective Studies; Quality of Life; Sciences de la santé humaine; Treatment Outcome; 5-FU resistant; irinotecan; CPT-11; chemotherapy; colon cancer; Antineoplastic agent; Human; Rectal disease; Carcinoma; Treatment efficiency; Fluoropyrimidine derivatives; Malignant tumor; Colonic disease; Irinotecan; Chemotherapy; Treatment; Rectum; Digestive diseases; Intestinal disease; Pyrimidine derivatives; Colon; Negative therapeutic reaction; Fluorouracil
• ISSN: 0959-8049; 1879-0852; 1879-0852
• DOI: 10.1016/S0959-8049(98)00353-0

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/m 2 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 ≥3 occurred in 7% of cycles and 28/107 (26%) of patients. CPT-11 350 mg/m 2 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.