title: Sensitivity to previous irinotecan treatment does not predict the efficacy of combination chemotherapy with cetuximab plus irinotecan for wild-type KRAS metastatic colorectal cancer.
abstract: The aim of this study was to evaluate the association of sensitivity to previous irinotecan-based chemotherapy with efficacy of cetuximab plus irinotecan therapy in metastatic colorectal cancer (MCRC) patients with wild-type KRAS. We analysed a pooled data set consisting of data from 87 MCRC patients from two previous phase II studies (n=60) and a group given off-protocol treatment (n=27) following irinotecan-, oxaliplatin-, and fluoropyrimidine-based chemotherapy. Overall objective response rate to cetuximab plus irinotecan was 28.7%, median progression-free survival (PFS) was 5.3 months, and median overall survival was 12.2 months. Objective response rate did not significantly differ between patients with a favourable response to previous irinotecan (n=23), stable disease (n=38), or progressive disease (n=26), with observed rates of 29.2%, 31.6%, and 23.1%, respectively. Additionally, the non-parametric Spearman rank correlation coefficients (ρ) between the PFS of previous irinotecan-based chemotherapy and that of cetuximab plus irinotecan were quite low (ρ=0.067 and 0.057 in patients with previous irinotecan as first- and second-line therapies, respectively). Although exploratory nature and small sample size may be limitations of this study, these findings indicate that the efficacy of irinotecan plus cetuximab in MCRC patients with wild-type KRAS did not differ by previous sensitivity to irinotecan.
authors.affiliation: Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan. kouheis0824@yahoo.co.jp
authors.forename: Kohei
authors.initials: K
authors.lastname: Shitara
authors.forename: Takashi
authors.initials: T
authors.lastname: Ura
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Daisuke
authors.initials: D
authors.lastname: Takahari
authors.forename: Tomoya
authors.initials: T
authors.lastname: Yokota
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yuki
authors.forename: Motoki
authors.initials: M
authors.lastname: Yoshida
authors.forename: Setsuo
authors.initials: S
authors.lastname: Utsunomiya
authors.forename: Yozo
authors.initials: Y
authors.lastname: Sato
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Yamaura
authors.forename: Mina
authors.initials: M
authors.lastname: Kato
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: 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; 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; D000068818:Cetuximab; D017322:Clinical Trials, Phase II as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D000077146:Irinotecan; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D002166:Camptothecin