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) |
|---|---|
| Pages (from-to) | 858-865 |
| Number of pages | 8 |
| Journal | Cancer Investigation |
| Volume | 22 |
| Issue number | 6 |
| DOIs | |
| State | Published - 2004 |
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Keywords
- Clinical trial
- Colorectal cancer
- HER-2/neu
- Irinotecan
- Trastuzumab
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
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 journal › Article
}
TY - JOUR
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
UR - http://www.scopus.com/inward/record.url?scp=10844274194&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=10844274194&partnerID=8YFLogxK
U2 - 10.1081/CNV-200039645
DO - 10.1081/CNV-200039645
M3 - Article
C2 - 15641483
AN - SCOPUS:10844274194
VL - 22
SP - 858
EP - 865
JO - Cancer Investigation
JF - Cancer Investigation
SN - 0735-7907
IS - 6
ER -