A randomized phase II trial of capecitabine and two different schedules of irinotecan in first-line treatment of metastatic colorectal cancer: efficacy, quality-of-life and toxicity

• Published in: Annals of oncology Vol. 16; no. 2; pp. 282 - 288
• Main Authors: Borner, M. M., Bernhard, J., Dietrich, D., Popescu, R., Wernli, M., Saletti, P., Rauch, D., Herrmann, R., Koeberle, D., Honegger, H., Brauchli, P., Lanz, D., Roth, A. D.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-02-2005
• Subjects: Adult; Aged; Antimetabolites, Antineoplastic - administration & dosage; Antimetabolites, Antineoplastic - adverse effects; Antimetabolites, Antineoplastic - therapeutic use; Antineoplastic agents; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - adverse effects; Antineoplastic Agents, Phytogenic - therapeutic use; Biological and medical sciences; Camptothecin - administration & dosage; Camptothecin - adverse effects; Camptothecin - analogs & derivatives; Camptothecin - therapeutic use; Capecitabine; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - pathology; Deoxycytidine - administration & dosage; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; Drug Administration Schedule; Female; Fluorouracil - analogs & derivatives; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Infusions, Intravenous; Irinotecan; Male; Medical sciences; metastatic colorectal cancer; Middle Aged; Pharmacology. Drug treatments; Quality of Life; randomized phase II; schedule; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Treatment Outcome; Tumors; Antineoplastic agent; Rectal disease; Capecitabine; Toxicity; Colorectal cancer; Metastasis; Randomization; Isomerases; Phase II trial; Intestinal disease; Clinical trial; Advanced stage; metastatic colorectal cancer; Pyrimidine nucleoside; Enzyme; Fluoropyrimidine derivatives; Treatment efficiency; DNA topoisomerase; Enzyme inhibitor; Malignant tumor; Induction treatment; Quality of life; First line treatment; Colonic disease; Irinotecan; schedule; randomized phase II; Digestive diseases
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdi047

Background: To determine the efficacy, impact on quality-of-life (QoL) and tolerability of two different irinotecan administration schedules in combination with capecitabine as first-line treatment of metastatic colorectal cancer. Patients and methods: We carried out a randomized phase II trial to select one of the following treatment regimens for further investigation: weekly irinotecan at a dose of 70 mg/m2 days 1, 8, 15, 22, 29 (arm A) or 3-weekly irinotecan at a dose of 300/240 mg/m2 day 1 and days 22 (arm B) in combination with capecitabine 1000 mg/m2 twice daily days 1–14 and days 22–35 every 6 weeks. Results: Seventy-five patients with good performance status entered the trial. The two arms were well balanced for relevant patient and disease characteristics. The most frequent toxic effects were grade 3/4 diarrhea (arm A: 34%, B: 19%), grade 3/4 neutropenia (A: 5%, B: 19%) and grade 2/3 alopecia (A: 26%, B: 65%). Other grade 3/4 toxic effects were rare (<5%). Response rates were 34% [95% confidence interval (CI) 20% to 51%] in arm A and 35% (95% CI: 20% to 53%) in arm B. Median time to progression was 6.9 (4.6–10.1) and 9.2 (7.9–11.5) months and median overall survival was 17.4 (12.6–23.0+) and 24.7 (16.3–26.4+) months. Patients with an objective tumor response reported better physical well-being (P < 0.01), mood (P < 0.05), functional performance (P < 0.05) and less effort to cope (P < 0.05) compared with the non-responders and stable disease patients. Conclusions: The primary end point of this study was the objective response rate and based on the statistical design of the trial, the 3-weekly irinotecan schedule was selected over weekly irinotecan administration. The 3-weekly irinotecan schedule also seemed advantageous in terms of grade 3/4 diarrhea, time to progression, overall survival and patient convenience, but the study was not designed to detect differences in these parameters. In addition, tumor response was shown to have a beneficial effect on QoL indicators.