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

Brigette B.Y. Ma, Stephen L. Chan, Wing M. Ho, Wilson Lau, Frankie Mo, Edwin P. Hui, Charles Chan, Annette Poon, Rasalkar D. Dattatray, Sze Chuen Cesar Wong, Ka F. To, Ann D. King, Anil Ahuja, Anthony T.C. Chan

Research output: Journal article publicationJournal articleAcademic researchpeer-review

12 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)4145-4153
Number of pages9
JournalCancer
Volume119
Issue number23
DOIs
Publication statusPublished - 1 Dec 2013

Keywords

  • amphiregulin
  • capecitabine
  • erlotinib
  • oxaliplatin
  • transforming growth factor alpha

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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