Results of a phase II trial of cetuximab plus capecitabine/irinotecan as first-line therapy for patients with advanced and/or metastatic colorectal cancer.
BACKGROUND
XELIRI (capecitabine/irinotecan) is effective and well tolerated in metastatic colorectal cancer (mCRC). Cetuximab is active in mCRC alone or with chemotherapy. This study evaluated cetuximab plus XELIRI in first-line treatment of mCRC.


METHODS
Subjects had histologically confirmed unresectable colorectal adenocarcinoma (with T4 lesions) after preoperative chemoradiation and/or metastases. Treatment was capecitabine 1700 mg/m2 (850 mg/m2 orally twice a day on days 1-14 for 3 weeks), irinotecan 200 mg/m2 intravenously (I.V.) on day 1 every 3 weeks, and weekly cetuximab (initially 400 mg/m2 I.V. [120 minutes], subsequently 250 mg/m2 [30 minutes]).


RESULTS
Baseline characteristics (N = 70): 43 men (61%); median age, 61.5 years; Eastern Cooperative Oncology Group performance status 0/1 = 66%/34%; 94% adenocarcinoma. Previous therapy: surgery (91%), chemotherapy (14%), or radiation therapy (7%). Responses (patients completing > or = 2 cycles): complete response (5.7%), partial response (37.7%), stable disease (43.4%), and progressive disease (PD; 13.2%); 16 patients discontinued early (n = 4 allergic reaction, n = 2 withdrew consent, n = 2 death, and n = 8 other adverse events [AEs]). The overall per-protocol response rate was 43.4% (34% intent to treat [ITT]; disease control rate, 86.8%; 69% ITT). The median time to progression was 8.1 months (range, < 1-27.0 months), and the median time to response was 1.6 months (range, 1.1-8.4 months). The median survival was 20.5 months, and 45.7% of patients remain alive. Of the 38 deaths, 84% were because of PD. No death was treatment related. The most frequent grade 3/4 treatment-related AEs included diarrhea, neutropenia, and nausea/vomiting; 32% of patients required dose reductions. All patients are off the study primarily because of PD (34.3%) or AEs (40.0%).


CONCLUSIONS
In summary, XELIRI plus cetuximab is a promising regimen that merits further study for first-line mCRC.
Cartwright
Thomas
T
US Oncology, Houston, TX, USA. thomas.cartwright@usoncology.com
Kuefler
Paul
P
Cohn
Allen
A
Hyman
William
W
Berger
Maury
M
Richards
Donald
D
Vukelja
Svetislava
S
Nugent
John E
JE
Ruxer
Robert L
RL
Boehm
Kristi A
KA
Asmar
Lina
L
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000069287:Capecitabine; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018450:Disease Progression; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003841:Deoxycytidine; D000069287:Capecitabine; D000077146:Irinotecan; D000068818:Cetuximab; D005472:Fluorouracil; D002166:Camptothecin