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ALTERNATING CPT-11 AND 5-FU/LV IN UNTREATED CRC
M.L. Rothenberg, MD, University of Texas Health Science Center, San Antonio, Tex, reported on 71 untreated metastatic colorectal cancer (CRC) patients. This multicenter Phase II trial used sequential intravenous infusions of CPT-11, also known as Camptosar (R) or irinotecan and 5-fluorouracil (5-FU) combined with leucovorin (LV).

Introduction CPT-11 inhibits topoisomerase 1 activity and has little cross resistance with 5-FU or LV. Topoisomerase 1 helps maintain DNA shape during translation, transcription, and replication. (See the monograph on Camptosar and FDA-approved package insert for full prescribing information).
Study protocol Seventy-one untreated metastatic CRC patients entered this multicenter study. The group consisted of 45 males and 26 females ranging in age from 22 to 84 years. Primary sites for the tumor were colon, 86% and rectum, 14%. Sites of metastases included liver, 80%, lymph nodes, 20%, lung, 13%, and adrenal glands, 13%.

Each 10-week dosing cycle began with an intravenous infusion of CPT-11 at 100 mg/m sq weekly, adjusted for tolerance, for 4 weeks. A two-week rest period followed. Then, 5-FU/LV was administered starting with 425 and 20 mg/m sq, respectively each day for 5 days with dose-adjustment, if needed. Each cyle concluded with a 3-week rest period. The 71 patients received a maximum of 6 cycles of combined treatment totalling 207 courses of CPT-11 and 169 courses of 5-FU/LV. Median dose intensities (mg/m sq/wk) were 66.7 for CPT-11, 530 for 5-FU, and 20 for LV.

Safety evaluation on each patient took place at least 6 times during CPT-11 treatment and twice while on 5-FU/LV. Tumor assessment occurred at baseline and after each 10-week dosing cycle.

Tumor response and survival Rothenberg reported 3 complete and 20 partial responses in the 71 treated patients for an overall response rate of 32.4%. CRC stabilized in 25/71 and progressed in 23/71. Six of 71 were alive after 6 cycles of combined treatment with CPT-11 and 5-FU/LV. The estimated median time to tumor progression was 6.9 months and median survival 17.8 months.
Toxicities Grade 3/4 leukopenia developed during CPT-11 therapy in 13% of patients during therapy with CPT-11 and 5% given 5-FU/LV. Corresponding grade 3/4 figures for neutropenia were 15% vs 12% and late diarrhea 20% vs 5%, respectively. The adverse reactions were expected considering the component medications. In Rothenberg's opinion, neither carryover nor cumulative toxicity occurred.
Conclusions The investigators view the results of this Phase II study as encouraging and support initiating Phase III trials either in the advanced or adjuvant setting. Currently, CPT-11 has FDA approval as monotherapy in metastatic CRC patients where the disease has progressed or recurred after 5-FU-based therapy.

For professional correspondence, please contact Dr. Rothenberg at: mace@oncology.uthscsa.edu

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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