title: A Phase II Study of XELOX and Cetuximab as First-Line Therapy in Patients With KRAS Wild Type Metastatic Colorectal Cancer (FLEET2 Study).
abstract: Despite the comparable clinical benefit of XELOX (capecitabine with oxaliplatin) and FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin), the value of XELOX treatment in combination with cetuximab for metastatic colorectal cancer (mCRC) remains largely unknown.
  
  
  
  In this clinical trial we evaluated the efficacy and safety of weekly/biweekly cetuximab administration combined with biweekly XELOX in patients with previously untreated v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) wild type mCRC. The primary end point was response rate (RR) with confirmation, and the secondary end points included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), dose intensity, and the safety of the protocol treatment.
  
  
  
  Forty patients who fulfilled the inclusion criteria participated in this study. The median treatment cycle number was 8 and the median dose intensities were 218 mg/m2/wk for cetuximab, 34 mg/m2/wk for oxaliplatin, and 821 mg/m2/d for capecitabine. One patient showed complete response and partial response was observed in 19 patients, giving an overall RR of 50% (95% confidence interval [CI], 33.8%-66.2%). Stable disease was obtained in 13 patients, resulting in a DCR of 82.5% (95% CI, 67.2%-92.7%). The PFS was 6.5 months (95% CI, 3.5-9.6 months), and the OS was 24.3 months (95% CI, 14.9-33.7 months). The safety profile revealed the common Grade 3/4 adverse events to be acneiform eruption (12.5%), peripheral neuropathy (7.5%), and elevated alanine transaminase levels (7.5%). Grade 3/4 thrombocytopenia and neutropenia occurred only in 5.0% and 2.5% of the patients, respectively. Grade 1 hand-foot syndrome (HFS) was not uncommon (20%), whereas Grade 2/3 HFS occurred in only 3 patients (7.5%). No deaths were reported within 30 days of the last dose.
  
  
  
  Cetuximab with XELOX showed a confirmed overall RR of 50%, which was within the previously reported range of RR. The safety profile showed an acceptable rate and severity of adverse events. In light of the several advantages of XELOX, including convenience and the reported cost-saving aspects, further study of this combination therapy is warranted.
authors: Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University, Graduate School of Medicine, Ube, Japan.
authors: Shoichi
authors: S
authors: Hazama
authors: Cancer Treatment Center, Kochi University, Nankoku, Japan. Electronic address: hmaeda@kochi-u.ac.jp.
authors: Hiromichi
authors: H
authors: Maeda
authors: Kansai Medical University Hirakata Hospital, Hirakata, Japan.
authors: Shigeyoshi
authors: S
authors: Iwamoto
authors: Division of Surgery, Osaka Rosai Hospital, Sakai, Japan.
authors: Ho Min
authors: HM
authors: Kim
authors: Department of Surgery, Kinki Central Hospital, Itami, Japan.
authors: Hiroyoshi
authors: H
authors: Takemoto
authors: Department of Surgery, Matsunami General Hospital, Hashima, Japan.
authors: Kenji
authors: K
authors: Kobayashi
authors: Tokai Central Hospital, Kakamigahara, Japan.
authors: Junichi
authors: J
authors: Sakamoto
authors: Kitakyushu General Hospital, Kitakyushu, Japan.
authors: Naoki
authors: N
authors: Nagata
authors: Department of Biostatistics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors: Koji
authors: K
authors: Oba
authors: Cancer Center, Aichi Medical University, Nagakute, Japan.
authors: Hideyuki
authors: H
authors: Mishima
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D000068818:Cetuximab / Q000008:administration & dosage / Q000009:adverse effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D010071:Oxaloacetates; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D010071:Oxaloacetates; D003841:Deoxycytidine; D000069287:Capecitabine; D016283:Proto-Oncogene Proteins p21(ras); D000068818:Cetuximab; D005472:Fluorouracil
keywords: Capecitabine; EGFR; Erbitax; HFS; Hand-foot symdrome