Low overexpression of HER-2/PPPNeu in advanced colorectal cancer limits the usefulness of trastuzumab (Herceptin®) and irinotecan as therapy. A phase II trial

Ramesh K. Ramanathan, Jimmy J. Hwang, William C. Zamboni, Frank A. Sinicrope, Howard Safran, Michael K. Wong, Martin Earle, Adam Brufsky, Terry Evans, Monica Troetschel, Christine Walko, Roger Day, Helen X. Chen, Sydney Finkelstein

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91 Scopus citations

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 languageEnglish (US)
Pages (from-to)858-865
Number of pages8
JournalCancer Investigation
Volume22
Issue number6
DOIs
StatePublished - Dec 31 2004

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Keywords

  • Clinical trial
  • Colorectal cancer
  • HER-2/neu
  • Irinotecan
  • Trastuzumab

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Ramanathan, R. K., Hwang, J. J., Zamboni, W. C., Sinicrope, F. A., Safran, H., Wong, M. K., Earle, M., Brufsky, A., Evans, T., Troetschel, M., Walko, C., Day, R., Chen, H. X., & Finkelstein, S. (2004). Low overexpression of HER-2/PPPNeu in advanced colorectal cancer limits the usefulness of trastuzumab (Herceptin®) and irinotecan as therapy. A phase II trial. Cancer Investigation, 22(6), 858-865. https://doi.org/10.1081/CNV-200039645