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Conrad Notes
a timely medical meeting newsletter
C. Pozzo, MD, Catholic University, Rome, Italy, presented a progress report on a multicenter Phase II study using CPT-11 alternating with 5-fluorouracil (5-FU)/folinic acid (FA) as first-line therapy. Thirty-three colorectal cancer (CRC) patients had one to eleven cycles of this regimen. Overall, the response rate was 30.3% and the median progression-free survival period 7.2 months. The incidence and severity of toxicities appears to be comparable to monotherapy with CPT-11 or 5-FU/FA. Further study may prove the regimen useful as first-line therapy.

Introduction Currently 5-FU is first-line therapy for advanced CRC. Added FA modulates the activity of 5-FU, according to Pozzo. CPT-11, a topoisomerase 1 inhibitor, has FDA approval for the treatment of CRC recurring or progressing after 5-FU-based therapy. (See package insert on irinotecan (Camptosar®). A study regimen using the three agents seems logical in view of the absence of cross-resistance and different mechanisms of action.
Study method Thirty-three adults (36 to 70 years) with confirmed metastatic CRC entered this Phase II study. In 82% of the patients, the colon was the primary tumor site and in 33% the rectum. Each 42-day cycle of treatment consisted of:

Day Therapy
1 Intravenous (iv) infusion of CPT-11 at 350 mg/m sq
2-21 Rest period - no treatment
22-26 Daily iv bolus injection of FA at 20 mg/m sq followed by 5-FU at 425 mg/m sq
27-42 Rest period - no treatment
Tumor assessment took place upon completion of each cycle and safety was evaluated throughout the study.
Efficacy in 33 CRC patients Following one to eleven (median = 6) treatment cycles, Pozzo reported the following responses in the 33 patients: complete, 1/33; partial, 9/33; stable disease,16/33; progressive disease, 3/33; and not evaluable, 4/33. The calculated response rate of 30.3% showed a 95% confidence interval of 15.6% to 48.7%.
Adverse reactions The observed severe (grade 3/4) incidence for diarrhea (24.2%) and neutropenia (63.6%), in Pozzo's opinion, appear comparable to corresponding percentages seen with CPT-11 or 5-FU/FA used as monotherapy in CRC patients. Other grade 3/4 toxicities were: stomatitis,9.1%; nausea/vomiting,9.0%; and constipation,6.0%. About 5% of the cycles required dose reduction.
Conclusions Pozzo and associates found alternating CPT-11 with 5-FU/FA to be well-tolerated by the 33 CRC patients. The results on efficacy suggest a promising antitumor effect in advanced CRC. Although preliminary, the data support further study.

For professional correspondence, please contact Dr. Pozzo at: cassano@rm.ats.it

Eugene A. Conrad

Presented at the Annual Meeting of the American Society of Clinical Oncology (ASCO) on May 17-20, 1997
CONRAD NOTES, © 1997 All Rights Reserved
Eugene A. Conrad, PhD, MPH / ISSN 1078 / June 1997

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