title: Prolonged survival of patients with metastatic colorectal cancer following first-line oxaliplatin-based chemotherapy with molecular targeting agents and curative surgery.
abstract: BACKGROUND
  The ability of molecular targeting agents to improve overall survival (OS) in metastatic colorectal cancer (MCRC) patients who underwent oxaliplatin-based chemotherapy remains controversial.
  
  
  METHODS
  We retrospectively analyzed 331 patients with MCRC who underwent first-line oxaliplatin-based chemotherapy. Treatment outcomes were compared between patients who started chemotherapy from April 2005 to March 2007 (cohort A; n = 157) and those who started it from April 2007 to March 2009 (cohort B; n = 174). To evaluate the impact of exposure to agents, we applied time-varying covariate analysis to avoid possible lead-time bias.
  
  
  RESULTS
  Median OS of cohorts A and B was 21.3 and 28.6 months, respectively (HR 0.66, 95% CI 0.50-0.87, p = 0.003). Exposure to bevacizumab (25 vs. 76%), anti-epidermal growth factor receptor (EGFR) (18 vs. 33%) or curative surgery after chemotherapy (4 vs. 10%) was significantly higher in cohort B. According to a multivariate Cox model with exposure to each agent or treatment as a time-varying covariate, hazard ratios of death were 0.71 (95% CI, 0.51-0.96; p = 0.03) for bevacizumab, 0.62 (95% CI, 0.40-0.89; p = 0.01) for anti-EGFR and 0.22 (95% CI, 0.06-0.57; p = 0.004) for surgery.
  
  
  CONCLUSIONS
  Increased exposure to molecular targeting agents or surgery after chemotherapy appears to contribute to an improvement in OS in recent patients with MCRC who have undergone oxaliplatin-based chemotherapy.
authors: Department of Clinical Oncology, Aichi Cancer Center Hospital, Chikusa-ku, Nagoya, Japan. kouheis0824@yahoo.co.jp
authors: Kohei
authors: K
authors: Shitara
authors: Keitaro
authors: K
authors: Matsuo
authors: Chihiro
authors: C
authors: Kondo
authors: Daisuke
authors: D
authors: Takahari
authors: Takashi
authors: T
authors: Ura
authors: Yoshitaka
authors: Y
authors: Inaba
authors: Hidekazu
authors: H
authors: Yamaura
authors: Yozo
authors: Y
authors: Sato
authors: Mina
authors: M
authors: Kato
authors: Yukihide
authors: Y
authors: Kanemitsu
authors: Koji
authors: K
authors: Komori
authors: Seiji
authors: S
authors: Ishiguro
authors: Tsuyoshi
authors: T
authors: Sano
authors: Yasuhiro
authors: Y
authors: Shimizu
authors: Kei
authors: K
authors: Muro
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D000068258:Bevacizumab; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D003131:Combined Modality Therapy; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D058990:Molecular Targeted Therapy; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068258:Bevacizumab; D066246:ErbB Receptors; D002955:Leucovorin; D005472:Fluorouracil