title: Intermittent versus continuous erlotinib with concomitant modified "XELOX" (q3W) in first-line treatment of metastatic colorectal cancer: correlation with serum amphiregulin and transforming growth factor alpha.
abstract: BACKGROUND
  This study evaluated the activity of 2 schedules of erlotinib in combination with chemotherapy, and the prognostic significance of serum amphiregulin (AREG) and transforming growth factor alpha (TGFa) in metastatic colorectal cancer.
  
  
  METHODS
  A total of 60 untreated patients were randomized to a "continuous" (CON; erlotinib 100 mg daily) or an "intermittent" (INT; erlotinib 150 mg on alternate day on day 2 to 14, then 150 mg daily on days 15 to 21) schedule of erlotinib with a modified XELOX (capecitabine plus oxaliplatin) regimen. Serum levels of AREG and TGFa were determined serially.
  
  
  RESULTS
  Baseline characteristics were similar between the 2 arms. Of the 58 patients evaluated for response, there was a nonsignificant trend toward a slightly higher overall response rate in the INT arm (66.7%) versus the CON arm (56.7%). At a median follow-up of 2.8 years, the median overall survival was 18.8 months (95% confidence interval = 11.3-22.9 months) and 20.7 months (95% confidence interval = 12.5-31 months, P = .19) for the CON and INT arm, respectively. KRAS mutation did not predict drug response. The 2 arms did not differ significantly in toxicity. Baseline serum TGFa was an independent predictor of progression-free survival, whereas a drop in serum TGFa and AREG levels following 3 to 4 cycles of treatment were associated with shorter progression-free survival and overall survival, respectively.
  
  
  CONCLUSIONS
  The intermittent erlotinib schedule was associated with a higher response rate, although this is not statistically significant. Serum TGFa and AREG levels have prognostic significance in erlotinib-treated patients with colorectal cancer, and further studies are warranted.
authors.affiliation: Department of Clinical Oncology, Sir Y.K. Pao Centre for Cancer, State Key Laboratory in Oncology in South China, Hong Kong Cancer Institute and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Brigette B Y
authors.initials: BB
authors.lastname: Ma
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Chan
authors.forename: Wing M
authors.initials: WM
authors.lastname: Ho
authors.forename: Wilson
authors.initials: W
authors.lastname: Lau
authors.forename: Frankie
authors.initials: F
authors.lastname: Mo
authors.forename: Edwin P
authors.initials: EP
authors.lastname: Hui
authors.forename: Charles
authors.initials: C
authors.lastname: Chan
authors.forename: Annette
authors.initials: A
authors.lastname: Poon
authors.forename: Rasalkar D
authors.initials: RD
authors.lastname: Dattatray
authors.forename: S C Cesar
authors.initials: SC
authors.lastname: Wong
authors.forename: Ka F
authors.initials: KF
authors.lastname: To
authors.forename: Ann D
authors.initials: AD
authors.lastname: King
authors.forename: Anil
authors.initials: A
authors.lastname: Ahuja
authors.forename: Anthony T C
authors.initials: AT
authors.lastname: Chan
mesh_terms: D000328:Adult; D000368:Aged; D066258:Amphiregulin; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D066255:EGF Family of Proteins; D000069347:Erlotinib Hydrochloride; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D010071:Oxaloacetates; D010349:Patient Compliance; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D011799:Quinazolines / Q000008:administration & dosage* / Q000633:toxicity; D016211:Transforming Growth Factor alpha / Q000097:blood*; D018631:ras Proteins / Q000235:genetics
chemical_list: C587848:AREG protein, human; D066258:Amphiregulin; D066255:EGF Family of Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C117307:KRAS protein, human; D010071:Oxaloacetates; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D011799:Quinazolines; D016211:Transforming Growth Factor alpha; D003841:Deoxycytidine; D000069287:Capecitabine; D000069347:Erlotinib Hydrochloride; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D005472:Fluorouracil
keywords: amphiregulin; capecitabine; erlotinib; oxaliplatin; transforming growth factor alpha