title: A short interval between bevacizumab and anti-epithelial growth factor receptor therapy interferes with efficacy of subsequent anti-EGFR therapy for refractory colorectal cancer.
abstract: BACKGROUND
  Both bevacizumab and anti-epithelial growth factor receptor (EGFR) agents (e.g. cetuximab and panitumumab) are sequentially used for metastatic colorectal cancer (mCRC). Their co-administration as a first-line treatment does not improve outcome, indicating that there are negative interactions between these agents. A long-term pharmacokinetics study demonstrated serum persistence of bevacizumab following termination of bevacizumab 6 months after the last administration. This prompted us to investigate the impact of short intervals between bevacizumab and anti-EGFR antibody on the efficacy of subsequent anti-EGFR therapy.
  
  
  METHODS
  We retrospectively reviewed consecutive patients with KRAS exon 2 wild-type mCRC who underwent anti-EGFR therapy after the failure of fluoropyrimidines, oxaliplatin and irinotecan. We divided patients into two groups (Group A: the interval between bevacizumab and anti-EGFR agent< 6 months; Group B: the interval >6 months).
  
  
  RESULTS
  Of the 114 included patients (median age, 63 years), 78 (68%) were male. Most patients (88%) were treated with cetuximab plus irinotecan. Groups A and B consisted of 74 and 40 patients, respectively. There were no significant differences in patient characteristics. Group B patients had significantly longer progression-free survival (4.2 vs. 6.6 months; HR, 0.65; 95% CI, 0.43-0.98; P = 0.038) and longer overall survival (11.6 vs. 14.3 months; HR, 0.63; 95% CI, 0.41-0.98, P = 0.039). The response rate was 24.3% in Group A and 47.5% in Group B (P = 0.012).
  
  
  CONCLUSIONS
  A short interval between bevacizumab and anti-EGFR antibody treatment may interfere with the efficacy of subsequent anti-EGFR therapy.
authors.affiliation: Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan h.taniguchi@aichi-cc.jp.
authors.forename: Hiroya
authors.initials: H
authors.lastname: Taniguchi
authors.affiliation: Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan.
authors.forename: Azusa
authors.initials: A
authors.lastname: Komori
authors.affiliation: Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan.
authors.forename: Yukiya
authors.initials: Y
authors.lastname: Narita
authors.affiliation: Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan.
authors.forename: Shigenori
authors.initials: S
authors.lastname: Kadowaki
authors.affiliation: Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ura
authors.affiliation: Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Andoh
authors.affiliation: Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yatabe
authors.affiliation: Department of Gastrointestinal Surgery, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Komori
authors.affiliation: Department of Gastrointestinal Surgery, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kimura
authors.affiliation: Department of Gastrointestinal Surgery, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kinoshita
authors.affiliation: Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan.
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; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000276:immunology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D000077544:Panitumumab; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D000077544:Panitumumab; D066246:ErbB Receptors; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
keywords: anti-EGFR antibody; bevacizumab; colorectal cancer; interval