title: Panitumumab in combination with irinotecan plus S-1 (IRIS) as second-line therapy for metastatic colorectal cancer.
abstract: BACKGROUND
  Irinotecan plus S-1 (IRIS) is the only oral fluoropyrimidine-based regimen reported to be non-inferior to FOLFIRI and widely used in clinical practice for metastatic colorectal cancer (mCRC) patients. However, the combination of IRIS plus an anti-EGFR agent has not been evaluated previously. This study aimed to investigate the feasibility and efficacy of IRIS with panitumumab as second-line therapy for wild-type KRAS mCRC.
  
  
  METHODS
  Main inclusion criteria were patients with wild-type KRAS mCRC refractory to one prior chemotherapy regimen for mCRC, ECOG PS 0-2, and age ≥20 years. Patients received panitumumab (6 mg/kg) and irinotecan (100 mg/m(2)) on days 1 and 15 and S-1 (40-60 mg according to body surface area) twice daily for 2 weeks, repeated every 4 weeks. The primary endpoint was the feasibility of the therapy. The secondary endpoints were response rate (RR), progression-free survival (PFS), and overall survival (OS).
  
  
  RESULTS
  A total of 36 patients received protocol treatment in eight centers. Of these, 23 patients (63.9 %) completed protocol treatment, demonstrating achievement of the primary endpoint. The most frequent grade 3/4 toxicities were diarrhea (16.7 %), acne-like rash (13.9 %), and neutropenia (11.1 %). The overall RR was 33.3 % (12/36). Of these patients, five underwent conversion surgery. Median PFS and OS were 9.5 months (95 % CI 3.5-15.4 months) and 20.1 months (95 % CI 16.7-23.2 months), respectively.
  
  
  CONCLUSIONS
  IRIS plus panitumumab has an acceptable toxicity profile and a promising efficacy in patients with previously treated wild-type KRAS mCRC. Accordingly, this regimen can be an additional treatment option for second-line chemotherapy in wild-type KRAS mCRC.
authors.affiliation: Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Toshi
authors.initials: T
authors.lastname: Takaoka
authors.affiliation: Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Department of Surgery, Shonan Kamakura General Hospital, 1370-1, Okamoto, Kamakura, Kanagawa, 247-8533, Japan.
authors.forename: Rai
authors.initials: R
authors.lastname: Shimoyama
authors.affiliation: Department of Surgery, Fukuoka Tokushukai Medical Center, 4-5, Sugukita, Kasuga, Fukuoka, 816-0864, Japan.
authors.forename: Shunji
authors.initials: S
authors.lastname: Kawamoto
authors.affiliation: Department of Surgery, Kishiwada Tokushukai Hospital, 4-27-1, Kamori-cho, Kishiwada, Osaka, 596-8522, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Sakamoto
authors.affiliation: Department of Integrated Medicine, Kagawa University Hospital, 1750-1, Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan.
authors.forename: Fuminori
authors.initials: F
authors.lastname: Goda
authors.affiliation: Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyamoto
authors.affiliation: Kochi Health Sciences Center, 2125-1 Ike, Kochi, 781-8555, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Negoro
authors.affiliation: Kobe City Medical Center General Hospital, 2-2-1, Minatojima, Minamimachi, Chuo-ku, Kobe, 650-0047, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Tsuji
authors.affiliation: Gastroenterology Center, Sapporo Higashi Tokushukai Hospital, 14-3-1, Higashi, Kita 33-jo, Higashi-ku, Sapporo, 065-0033, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Yoshizaki
authors.affiliation: Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Goji
authors.affiliation: Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kitamura
authors.affiliation: Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yano
authors.affiliation: Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Kimura
authors.affiliation: Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Okahisa
authors.affiliation: Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Muguruma
authors.affiliation: Department of Molecular Target Exploration, Sapporo Medical University School of Medicine, South-1, West-17, Chuo-ku, Sapporo, 060-8556, Japan.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Niitsu
authors.affiliation: Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan. takayama@tokushima-u.ac.jp.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Takayama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D004338:Drug Combinations; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010094:Oxonic Acid / Q000008:administration & dosage; D000077544:Panitumumab; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D015996:Survival Rate; D005641:Tegafur / Q000008:administration & dosage
chemical_list: D000911:Antibodies, Monoclonal; D004338:Drug Combinations; C117307:KRAS protein, human; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000077544:Panitumumab; D000077146:Irinotecan; D016283:Proto-Oncogene Proteins p21(ras); D002166:Camptothecin
keywords: Chemotherapy; Colorectal cancer; Irinotecan; Panitumumab; S-1