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

Ramesk 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

Research output: Contribution to journalArticle

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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 - 2004

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irinotecan
Colorectal Neoplasms
Diarrhea
Pharmacokinetics
Therapeutics
Drug Therapy
Leukopenia
Dehydration
Acute Kidney Injury
Nausea
Vomiting
Heart Failure
Immunohistochemistry
Trastuzumab

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Low overexpression of HER-2/PPPNeu in advanced colorectal cancer limits the usefulness of trastuzumab (Herceptin®) and irinotecan as therapy. A phase II trial. / Ramanathan, Ramesk K; Hwang, Jimmy J.; Zamboni, William C.; Sinicrope, Frank A; Safran, Howard; Wong, Michael K.; Earle, Martin; Brufsky, Adam; Evans, Terry; Troetschel, Monica; Walko, Christine; Day, Roger; Chen, Helen X.; Finkelstein, Sydney.

In: Cancer Investigation, Vol. 22, No. 6, 2004, p. 858-865.

Research output: Contribution to journalArticle

Ramanathan, RK, Hwang, JJ, Zamboni, WC, Sinicrope, FA, Safran, H, Wong, MK, Earle, M, Brufsky, A, Evans, T, Troetschel, M, Walko, C, Day, R, Chen, HX & 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, vol. 22, no. 6, pp. 858-865. https://doi.org/10.1081/CNV-200039645
Ramanathan, Ramesk K ; Hwang, Jimmy J. ; Zamboni, William C. ; Sinicrope, Frank A ; Safran, Howard ; Wong, Michael K. ; Earle, Martin ; Brufsky, Adam ; Evans, Terry ; Troetschel, Monica ; Walko, Christine ; Day, Roger ; Chen, Helen X. ; Finkelstein, Sydney. / Low overexpression of HER-2/PPPNeu in advanced colorectal cancer limits the usefulness of trastuzumab (Herceptin®) and irinotecan as therapy. A phase II trial. In: Cancer Investigation. 2004 ; Vol. 22, No. 6. pp. 858-865.
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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.",
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T1 - Low overexpression of HER-2/PPPNeu in advanced colorectal cancer limits the usefulness of trastuzumab (Herceptin®) and irinotecan as therapy. A phase II trial

AU - Ramanathan, Ramesk K

AU - Hwang, Jimmy J.

AU - Zamboni, William C.

AU - Sinicrope, Frank A

AU - Safran, Howard

AU - Wong, Michael K.

AU - Earle, Martin

AU - Brufsky, Adam

AU - Evans, Terry

AU - Troetschel, Monica

AU - Walko, Christine

AU - Day, Roger

AU - Chen, Helen X.

AU - Finkelstein, Sydney

PY - 2004

Y1 - 2004

N2 - 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.

AB - 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.

KW - Clinical trial

KW - Colorectal cancer

KW - HER-2/neu

KW - Irinotecan

KW - Trastuzumab

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DO - 10.1081/CNV-200039645

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JF - Cancer Investigation

SN - 0735-7907

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