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T. Iveson, MD, Royal South Hants NHS Trust, Southampton, UK, and 63 other UK clinical oncologists studied CPT-11 (irinotecan) in 148 advanced colorectal cancer (CRC) patients resistant to 5-fluorouracil (5-FU). CPT-11 followed the European schedule of 350 mg/msq intravenously every 3 weeks. Early data analysis show 6- and 12-month survival rates of 64% and 35%, respectively. Adverse events occurred as reported in phase II and III studies. Please see the related reports of Van Cutsem and Cunningham in this issue of Conrad Notes. The US package insert on irinotecan (Camptosar®) is available for full prescribing information.
Introduction to the evaluation CPT-11, the first licensed topoisomerase 1 inhibitor, is effective in treating advanced CRC patients failing to respond to 5-FU. The phase III trials of Van Cutsem and Cunningham confirm the 7 phase II studies for safety and efficacy. Iveson and collaborating oncologists sought to determine the clinical benefit of CPT-11 in 53 UK community cancer units.
Patient flow chart The 64 participating oncologists enrolled 174 CRC patients resistant to 5-FU therapy to yield 108 evaluable for effectiveness:
Iveson chart
All 148 patients received at least one course of CPT-11 and provided adverse drug event (ADE) information.
Tumor response in 108 evaluable patients The median number of CPT-11 administered cycles was 4 (range,1-14+). Forty-seven of 148 treated (32%) received 6 or more cycles. The overall response rate (RR) in evaluable patients was 27%. Further analysis shows complete RR in 2 (2%), partial in 27 (25%), and stable disease in 62 (57%).

Kaplan-Meier survival curves followed. The estimated overall survival for the 148 patients on CPT-11 is 259 days. At 6 months, these patients had a 64% probability of survival and at 12 months, 35%. Iveson cautions that the survival data are still immature with 69% unavailable at the 400-day time point. However, the study results are consistent with available phase II and III data.

Adverse events (ADEs) in 148 treated patients There were no unanticipated adverse events. Moderate to severe ADEs were: diarrhea (12%), vomiting (6%), nausea (5%), alopecia (4%), and 2% each for leukopenia, abdominal pain, asthenia, and somnolence, and cholinergic symptoms (1%). The same ADEs occurred as mild about 3 to 7 times as often. Iveson noted a cholinergic syndrome in 16% of the patients. Also, one patient each died from pneumonia/septicemia, renal failure, and neutropenia -- interpreted as treatment-related by the reporting doctor.
Presenter summary and conclusions The data demonstrate that open label CPT-11 treatment of advanced CRC patients resistant to 5-FU:
  • Controlled tumor growth in 84% of 108 evaluable patients
  • Led to ADEs as noted before in phase II and III studies
  • Required dose reduction in only 13 (9%) although ADEs occurred in 76% of 148 patients
Conrad comments This study llustrates real-world use of high dose CPT-11 in the clinic. The results confirm and extend data collected under more stringent conditions, as obtained in the 7 phase II studies and two clinical trials described by Van Cutsem and Cunningham. Experience coupled with clinical research data support making CPT-11 standard treatment for 5-FU-resistant CRC.
For professional correspondence, please contact Dr. Iveson by Fax at: 170 382 5441 or E-mail at: tjive@lineone.net

Eugene A. Conrad

Presented at the American Society of Clinical Oncology (ASCO) Meeting, May 16-19, 1998
Copyright © 1998 Conrad Group Inc. All Rights Reserved
Eugene A. Conrad, PhD, MPH / ISSN 1078-2230 / June 1998
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