title: Low overexpression of HER-2/neu in advanced colorectal cancer limits the usefulness of trastuzumab (Herceptin) 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.
  
  
  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 i.v. and 2 mg/kg thereafter). Irinotecan 125 mg/m2, i.v. 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.
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15232, USA. ramanathanrk@msx.upmc.edu
authors.forename: Ramesh K
authors.initials: RK
authors.lastname: Ramanathan
authors.forename: Jimmy J
authors.initials: JJ
authors.lastname: Hwang
authors.forename: William C
authors.initials: WC
authors.lastname: Zamboni
authors.forename: Frank A
authors.initials: FA
authors.lastname: Sinicrope
authors.forename: Howard
authors.initials: H
authors.lastname: Safran
authors.forename: Michael K
authors.initials: MK
authors.lastname: Wong
authors.forename: Martin
authors.initials: M
authors.lastname: Earle
authors.forename: Adam
authors.initials: A
authors.lastname: Brufsky
authors.forename: Terry
authors.initials: T
authors.lastname: Evans
authors.forename: Monica
authors.initials: M
authors.lastname: Troetschel
authors.forename: Christine
authors.initials: C
authors.lastname: Walko
authors.forename: Roger
authors.initials: R
authors.lastname: Day
authors.forename: Helen X
authors.initials: HX
authors.lastname: Chen
authors.forename: Sydney
authors.initials: S
authors.lastname: Finkelstein
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000077146:Irinotecan; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D002166:Camptothecin; D000077146:Irinotecan; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab