@article{9ff7bb5043214f2e956591fec83dbbc0,
title = "Low overexpression of HER-2/PPPNeu in advanced colorectal cancer limits the usefulness of trastuzumab (Herceptin{\textregistered}) and irinotecan as therapy. A phase II trial",
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{\texttrademark}). 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.",
keywords = "Clinical trial, Colorectal cancer, HER-2/neu, Irinotecan, Trastuzumab",
author = "Ramanathan, {Ramesh K.} and Hwang, {Jimmy J.} and Zamboni, {William C.} and Sinicrope, {Frank A.} and Howard Safran and Wong, {Michael K.} and Martin Earle and Adam Brufsky and Terry Evans and Monica Troetschel and Christine Walko and Roger Day and Chen, {Helen X.} and Sydney Finkelstein",
note = "Funding Information: 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 #Presented in part at the 37th Annual Meeting of the American Society of Clinical Oncology, San Francisco, CA, May 12, 2001. †This study was sponsored by the Cancer Therapy and Evaluation Program of the National Cancer Institute and supported in part by NIH/NCCR/GCRC/#5MO1 RR00056; NCI 2P30 CA 479004 to the University of Pittsburgh Cancer Institute and grants from Genentech Inc. and Pharmacia and Upjohn. ††Current author affiliations: Jimmy J. Hwang, M.D., Department of Medicine, Georgetown University, Washington, DC, USA; Frank A. Sinicrope, M.D., Mayo Clinic, Rochester, Minnesota, USA; Michael K. Wong, Roswell Park Cancer Institute, Buffalo, New York, USA. *Correspondence: Ramesh K. Ramanathan, M.D., University of Pittsburgh Cancer Institute, UPMC Cancer Pavilion, 5150 Centre Ave., # 562, Pittsburgh, PA 15232, USA; Fax: (412) 648-6579; E-mail: ramanathanrk@msx.upmc.edu.",
year = "2004",
doi = "10.1081/CNV-200039645",
language = "English (US)",
volume = "22",
pages = "858--865",
journal = "Cancer Investigation",
issn = "0735-7907",
publisher = "Informa Healthcare",
number = "6",
}