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R. Pazdur, MD, The M D Anderson Cancer Center, Houston, Tex, found increased age is not a risk factor in dosing colon cancer (CRC) patients with CPT-11. Retrospective analysis of pivotal studies in the FDA submission suggested a higher frequency of first-course grade 3/4 diarrhea in the elderly (p=0.047). The present study on 182 patients showed that using similar doses of CPT-11 (Camptosar [R], irinotecan) led to lower frequencies in the elderly than seen in the pivotal studies on 193 patients. Please consult the Package Insert for prescribing information.

Dosing with CPT-11 Each patient with progressive CRC after 5-fluorouracil (5-FU) therapy started with the projected CPT-11 dose of 125 mg/m sq weekly x 4 weeks as a 90-minute infusion followed by two week' rest. Four 6-week courses ensued with dosing individualized as tolerated. Supportive care consisted of dexamethasone and 5-HT blockers for emesis, atropine for cholinergic syndrome, loperamide for late diarrhea, and granulocyte macrophage colony stimulating factor (GM-GSF) for neutropenic fever (sepsis).
Distribution of Patients The <65 year-old group included 52 males and 40 females with an overall median age of 56 years. Forty-six males and 44 females made up the elderly group with an overall median age of 70 years. Before study entry, all patients showed progressive CRC after 5-FU therapy.
Administered doses of CPT-11 The median weekly dose of CPT-11 used in this study on 182 patients was similar to that of the 125 mg/m sq group of 193 patients in the original pivotal studies. Expressed as mg/m sq for course #1, these were 79 vs 75 in the under 65 group and 71 vs 60 for the elderly. None of the differences was statistically significant (p>0.05); the same conclusion held after comparison of all course data.
Grade 3/4 late diarrhea Twelve per cent of the 65 year-old CRC patients developed late first course grade 3/4 diarrhea in the present study, a rate similar to the 21% noted in the pivotal studies (p>0.05). Examination of data on all administered courses showed rates of 17% and 25%, respectively (p>0.05).

The elderly patients in this study experienced less late grade 3/4 diarrhea than in the pivotal studies. First course CPT-11 led to an 18% response in the present study compared with 34% seen previously (p<0.02) and 17% vs 25% for all courses (p<0.02), respectively.

Other CPT-11 toxicities Weekly hematologic and other safety assessments were conducted throughout this study.

The frequencies of late first-course grade 3/4 toxicities seen in the 182 patients in the current study compared with the pivotal studies were: nausea,12.6% vs 14.5%; asthenia, 11.5% vs 6.2%; neutropenia,13.7% vs 24.3%; and leukopenia,33.5% vs 19.2%, respectively.

Tumor evaluation CT scan examination took place at baseline, 6 wks, 12 wks, and every 12 wks while receiving CPT-11 for a total of 5 courses. Overall, the current study and the pivotal studies showed comparable response rates of 10.4% (95% CI, 6.0-14.9) and 15.0% (95% CI, 10.0-20.1), respectively. Subgroup analyses by age detected a <1.0% difference between the elderly and the <65 year-olds in both studies.
Conclusions Pazdur and coinvestigators found the starting CPT-11 dose of 125 mg/m sq appropriate for adult patients regardless of age. However, attention to patient education and close safety monitoring is imperative as for other chemotherapies.

For professional correspondence, please contact Dr. Pazdur at: rpazdur@notes.mdacc.tmc.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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