Irinotecan is an active agent in untreated patients with metastatic colorectal cancer Journal Article
| Authors: | Conti, J. A.; Kemeny, N. E.; Saltz, L. B.; Huang, Y.; Tong, W. P.; Chou, T. C.; Sun, M.; Pulliam, S.; Gonzalez, C. |
| Article Title: | Irinotecan is an active agent in untreated patients with metastatic colorectal cancer |
| Abstract: | Purpose: To determine the response rate, survival, and toxicity of the new anticancer agent, irinotecan (CPT-11), in the treatment of metastatic colorectal cancer. Patients and Methods: Forty-one chemotherapy-naive patients with measurable metastatic colorectal cancer were treated with a 90- minute infusion of irinotecan 125 mg/m2 administered weekly for 4 weeks every 6 weeks. Pretreatment tumor biopsies to assess topoisomerase-I (Topo- I) activity were obtained from 11 patients. The pharmacokinetics far irinotecan and its active metabolite, SN-38, were determined in 18 patients. Results: Thirteen of 41 patients (32%) had a partial response (PR; 95% confidence interval, 18% to 46%). The median response duration was 8.1 months (range, 4.0 to 16.0) and the median survival time was 12.1 months (range, 2.1 to 21.7) for all 41 patients. Grade 3 or 4 toxicities were diarrhea (29% of patients) and neutropenia (22% of patients). Grade 3 or 4 diarrhea was substantially more prevalent in the initial 18 patients on study, with an incidence rate of 56%; a significant reduction in the incidence of severe diarrhea to 9% was noted with strict adherence to an antidiarrheal regimen of loperamide and diphenhydramine. No correlations were seen between pharmacokinetics of irinotecan/SN-38 and the clinical parameters of response, survival, or incidence of diarrhea. Conclusions: Irinotecan has activity in the treatment of patients with metastatic colorectal cancer. Strict adherence to an antidiarrheal regimen of diphenhydramine/loperamide significantly reduced the incidence of diarrhea; the agent was thereafter well tolerated in the majority of patients. |
| Keywords: | adult; cancer chemotherapy; cancer survival; clinical article; human tissue; aged; aged, 80 and over; middle aged; survival analysis; human cell; clinical trial; neutropenia; diarrhea; drug efficacy; antineoplastic agent; colorectal cancer; drug administration schedule; 7 ethyl 10 hydroxycamptothecin; antineoplastic agents, phytogenic; camptothecin; colonic neoplasms; dexamethasone; irinotecan; survival time; liver; lung; remission induction; ondansetron; loperamide; rectal neoplasms; atropine; intravenous drug administration; dna topoisomerase; oral drug administration; diphenhydramine; humans; human; male; female; priority journal; article |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 14 |
| Issue: | 3 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 1996-03-01 |
| Start Page: | 709 |
| End Page: | 715 |
| Language: | English |
| PUBMED: | 8622015 |
| PROVIDER: | scopus |
| DOI: | 10.1200/JCO.1996.14.3.709 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 22 November 2017 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work