Results Similar With Weekly or Every-3-Week Irinotecan Dosing Regimens

August 1, 2002

ORLANDO-Irinotecan, also known as CPT-11 (Camptosar), administered every 3 weeks to patients with fluorouracil (5-FU)-refractory colorectal cancer produced response rates and toxicity profiles similar to irinotecan given weekly in a phase

ORLANDO—Irinotecan, also known as CPT-11 (Camptosar), administered every 3 weeks to patients with fluorouracil (5-FU)-refractory colorectal cancer produced response rates and toxicity profiles similar to irinotecan given weekly in a phase III study. Charles S. Fuchs, MD, MPH, Dana-Farber Cancer Institute, reported the results at the 38th Annual Meeting of the American Society of Clinical Oncology (abstract 514).

"Our findings are consistent with other efficacy results of phase III trials of single agent CPT-11 in 5-FU-refractory colorectal cancer," Dr. Fuchs said. "In addition, these results continue to support the close monitoring of patients treated with CPT-11."

Patients were randomized in a 1:2 ratio to weekly or every 3-week irinotecan. The first group received a weekly schedule of 125 mg/m² for 4 consecutive weeks followed by a 2-week rest. The second arm was given 350 mg/m² every 3 weeks.

Patients who were age 70 or older, had a performance status of 2, or had received prior pelvic radiotherapy started irinotecan at 300 mg/m². About 55% of the patients in the 3-week arm started at the lower dose.

Patients were managed with antiemetics and antidiarrheal medication as needed and atropine for cholinergic symptoms during the infusion. Prophylactic atropine was not permitted during the first treatment infusion.

Eligibility included patients with measurable metastatic colorectal cancer that had progressed within 6 months of 5-FU-based chemotherapy for metastatic disease or had relapsed within 12 months of adjuvant 5-FU therapy. Patients also were required to have an ECOG performance status of 2 or less and adequate laboratory parameters, including a serum bilirubin of no greater than 1.5 mg/dL. Researchers excluded patients treated in the past with irinotecan.

Primary Endpoint

The primary endpoint was 1-year survival. Secondary endpoints included time to progression, overall survival, toxicity, and quality of life. Researchers used an intention-to-treat analysis for efficacy and quality-of-life endpoints. Tumors were measured every 6 weeks through week 18 and then every 12 weeks until disease progression. Researchers assessed quality of life at the start, every 6 weeks during the trial, and when treatment was discontinued.

Twenty-nine US centers enrolled 291 patients, 95 to weekly chemotherapy and 196 to the 3-week schedule; 26% had received prior pelvic radiation, and 24% had failed adjuvant 5-FU.

Patients in both arms experienced similar 1-year survival rates and time to progression. At 1 year, 46% of patients receiving weekly irinotecan were alive as were 41% of those on the 3-week schedule (P = .42). "Overall survival also did not differ between treatment groups," Dr. Fuchs said. "In both arms, median overall survival was 9.9 months."

All patients who received treatment were included in the evaluation of adverse events. First-infusion cholinergic events affected 31% of patients in the weekly arm and 61% in the every-3-week cohort. In contrast, throughout therapy, grade 3-4 late diarrhea was significantly more common in patients on the weekly schedule (36% vs 19%).

Vomiting and neutropenia were slightly more common in the every-3-week group, but this difference did not reach statistical significance.

"During the treatment period, five patients receiving weekly therapy (5.2%) and three patients given every-3-week therapy (1.5%) died of causes that were considered to be possibly drug related," Dr. Fuchs said. "This difference in treatment-related deaths did not reach statistical significance with a P value of .12."

A higher proportion of patients on the weekly schedule required dose reduction. In the weekly cohort, 51% received full dose at week 3 and 35% at week 4. In the every-3-week arm, 69% received full dose at week 4.

Quality-of-life questionnaires were returned by 84% of patients, with similar responses between the two arms.

"Compared to the weekly schedule of CPT-11, every-3-week therapy was associated with a similar overall survival and time to progression, as well as a similar quality of life," Dr. Fuchs concluded. "However, every-3-week CPT-11 was associated with a significantly lower rate of grade 3 diarrhea."