Abstract
Background: To determine the response rate of trastuzumab and irinotecan in HER-2/neu overexpressing advanced colorectal cancer (CRC), determine the frequency of HER-2/neu expression in CRC, and evaluate the pharmacokinetics of trastuzumab in a phase II study. Patients and Methods: Patients were screened for HER-2/neu by immunohistochemistry (DAKO HercepTest™). Prior chemotherapy was limited to one regimen. Trastuzumab was administered weekly (loading dose of 4 mg/kg IV and 2 mg/kg thereafter). Irinotecan 125 mg/m 2, IV was administered weekly for 4 weeks with a 2-week rest period. Results: HER-2/neu overexpression was detected in 11 of 138 (8.0%) of screened tumors (2+ in 5 and 3+ in 6 patients). Nine patients were entered in the study; 6 had received prior chemotherapy. Partial responses were seen in 5 of 7 evaluable patients. Grade 3-4 toxicities in 31 cycles of therapy included diarrhea (19%), nausea (10%), and vomiting (6%). Leukopenia occurred in 6%, and congestive heart failure and acute renal failure (secondary to diarrhea and dehydration) were seen in 3% of cycles. The study was prematurely closed due to low accrual. Conclusions: The low overexpression rate of HER-2/neu (8.0%) in advanced CRC limits the potential for further investigation of regimens involving trastuzumab, despite evidence suggestive of activity. Irinotecan did not alter the pharmacokinetic disposition of trastuzumab.
Original language | English (US) |
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Pages (from-to) | 858-865 |
Number of pages | 8 |
Journal | Cancer Investigation |
Volume | 22 |
Issue number | 6 |
DOIs | |
State | Published - Dec 31 2004 |
Keywords
- Clinical trial
- Colorectal cancer
- HER-2/neu
- Irinotecan
- Trastuzumab
ASJC Scopus subject areas
- Oncology
- Cancer Research