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

Authors

  • Brigette B. Y. Ma FRACP,

    Corresponding author
    1. 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
    • Corresponding author: Brigette Ma, FRACP, Department of Clinical Oncology, Prince of Wales Hospital, Shatin, New Territories, Hong Kong, SAR, China; Fax: 011 (852) 26487097; brigette@clo.cuhk.edu.hk

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  • Stephen L. Chan MRCP,

    1. 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
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  • Wing M. Ho MRCP,

    1. 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
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  • Wilson Lau RN,

    1. 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
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  • Frankie Mo PhD,

    1. 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
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  • Edwin P. Hui MD,

    1. 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
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  • Charles Chan PhD,

    1. 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
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  • Annette Poon FRACP,

    1. 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
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  • Rasalkar D. Dattatray MD,

    1. Department of Imaging and Interventional Radiology, Prince of Wales Hospital, Hong Kong SAR, China
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  • S. C. Cesar Wong PhD,

    1. Department of Health Technology and Informatics, the Hong Kong Polytechnic University, Hong Kong SAR, China
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  • Ka F. To FRCPA,

    1. Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong SAR, China
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  • Ann D. King FRCR,

    1. Department of Imaging and Interventional Radiology, Prince of Wales Hospital, Hong Kong SAR, China
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  • Anil Ahuja FRCR,

    1. Department of Imaging and Interventional Radiology, Prince of Wales Hospital, Hong Kong SAR, China
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  • Anthony T. C. Chan MD

    1. 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
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  • This work was presented in part as a poster at the 35th European Society of Medical Oncology Annual Congress, October 8-12, 2010, Milan, Italy.

  • This work was also presented as a poster at the American Society of Clinical Oncology GI Cancer Symposium 2013, San Francisco, CA, USA, abstract 425.

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. Cancer 2013;119:4145–4153. © 2013 American Cancer Society.

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