title: Phase II study of combination chemotherapy with biweekly cetuximab and irinotecan for wild-type KRAS metastatic colorectal cancer refractory to irinotecan, oxaliplatin, and fluoropyrimidines.
abstract: The aim of this study is to prospectively evaluate the efficacy of combination chemotherapy with every second week cetuximab and irinotecan in patients with pretreated metastatic colorectal cancer harboring wild-type KRAS. Patients with wild-type KRAS metastatic colorectal cancer that had progressed after chemotherapy with irinotecan, oxaliplatin, and fluoropyrimidine were included. Cetuximab was administered at 500 mg/m(2) biweekly with irinotecan. The primary endpoint was response rate. The pharmacokinetics of cetuximab was also evaluated in 5 patients. From May 2009 to February 2010, a total of 31 patients were enrolled from five institutions. One patient was not eligible. Among the 30 patients who were treated with biweekly cetuximab plus irinotecan, partial response was observed in 9 patients. The objective response rate was 30.0% (95% confidence interval [CI], 14.7%-49.4%) and the disease control rate (complete response, partial response, or stable disease) was 76.7% (95% CI, 57.7%-90.0%). The median progression-free survival was 5.3 months and median overall survival was 10.8 months. Grade 3 skin toxicity was observed in 3 patients (10.0%) and one treatment related death due to pneumonia was observed. Combination chemotherapy with biweekly cetuximab and irinotecan was effective for pretreated metastatic colorectal cancer with wild-type KRAS.
authors.affiliation: Department of Clinical Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi Prefecture 464-8681, Japan. Kouheis0824@yahoo.co.jp
authors.forename: Kohei
authors.initials: K
authors.lastname: Shitara
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yuki
authors.forename: Motoki
authors.initials: M
authors.lastname: Yoshida
authors.forename: Daisuke
authors.initials: D
authors.lastname: Takahari
authors.forename: Setsuo
authors.initials: S
authors.lastname: Utsunomiya
authors.forename: Tomoya
authors.initials: T
authors.lastname: Yokota
authors.forename: Yozo
authors.initials: Y
authors.lastname: Sato
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Inaba
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tajika
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kawai
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Yamaura
authors.forename: Mina
authors.initials: M
authors.lastname: Kato
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Komatsu
authors.forename: Kei
authors.initials: K
authors.lastname: Muro
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004338:Drug Combinations; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D007564:Japan; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010094:Oxonic Acid / Q000008:administration & dosage; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D005641:Tegafur / Q000008:administration & dosage; D017211:Treatment Failure; D018631:ras Proteins / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D004338:Drug Combinations; C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D011518:Proto-Oncogene Proteins; D000077150:Oxaliplatin; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000077146:Irinotecan; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D005472:Fluorouracil; D002166:Camptothecin