title: First-line cetuximab-based chemotherapies for patients with advanced or metastaticKRASwild-type colorectal cancer.
abstract: Colorectal cancer (CRC) is one of the most commonly occurring cancers worldwide. A burgeoning number of studies have demonstrated that the addition of cetuximab to another standard first-line regimen markedly improves the outcome of CRC treatment. However, at present, the efficacy and safety of cetuximab-based combination chemotherapy has not been well described in Japan. The aim of the present study was to evaluate the efficacy and safety of first-line chemotherapies that included cetuximab for patients with advanced or metastatic Kirsten rat sarcoma viral oncogene homolog (KRAS) wild-type CRC in Japan. This prospective multicenter observational study was conducted at 13 affiliated medical institutions. A total of 64 patients were enrolled between 2010 and 2013. The patients met the following criteria for eligibility: i) histologically confirmed, advanced or metastaticKRASwild-type CRC; and ii) cetuximab-based chemotherapies administered as a first-line treatment. First-line cetuximab-based treatments were administered as follows: 29 patients (45.3%) received a combination of infusional fluorouracil, leucovorin and oxaliplatin; 14 patients (21.9%) received a combination of capecitabine and oxaliplatin; and 10 patients (15.6%) received a combination of infusional fluorouracil, leucovorin and irinotecan. The overall response rate (including complete plus partial responses) was 50% (32/64 patients). Initially, 48 lesions were diagnosed as unresectable. Among those, 13 lesions (27.1%) were converted to a resectable status following cetuximab-based combination chemotherapy treatments. The median overall survival time and the progression-free survival time were 1,189 and 359 days, respectively. The most frequent grade 3/4 adverse event was neutropenia, which occurred in 20.3% of the patients. The incidence of grade 3/4 skin toxicity was 17.2% (11/64 patients). Cetuximab-based therapies may represent a promising first-line regimen for patients with advanced or metastaticKRASwild-type CRC in Japan. In addition, this combination was associated with a low incidence of serious toxicities.
authors.affiliation: Department of Surgery, National Hospital Organization, Osaka National Hospital, Osaka 540-0006, Japan; Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Uemura
authors.affiliation: Department of Surgery, Osaka Rosai Hospital, Osaka 591-8025, Japan; Department of Surgery, Rinku General Medical Center, Osaka 598-8577, Japan.
authors.forename: Ho Min
authors.initials: HM
authors.lastname: Kim
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Hata
authors.affiliation: Department of Surgery, Higashiosaka City General Hospital, Osaka 578-8588, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Sakata
authors.affiliation: Department of Surgery, Higashiosaka City General Hospital, Osaka 578-8588, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Okuyama
authors.affiliation: Department of Surgery, Sakai City Medical Center, Osaka 593-8304, Japan.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Takemoto
authors.affiliation: Department of Surgery, Rinku General Medical Center, Osaka 598-8577, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Fujii
authors.affiliation: Department of Surgery, Ikeda Municipal Hospital, Osaka 563-8510, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Fukuzaki
authors.affiliation: Department of Surgery, Nissei Hospital, Osaka 550-0012, Japan.
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Morita
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Taishi
authors.initials: T
authors.lastname: Hata
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takemasa
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan; Department of Frontier-Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Taroh
authors.initials: T
authors.lastname: Satoh
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Tsunekazu
authors.initials: T
authors.lastname: Mizushima
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Maski
authors.initials: M
authors.lastname: Mori
keywords: KRAS wild-type; cetuximab; colorectal cancer; first-line chemotherapy; irinotecan; oxaliplatin