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Soluble FAS in the prediction of benefit from cetuximab and irinotecan for patients with advanced colorectal cancer

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Abstract

The FAS/FASL system, comprising membrane-bound (mFAS and mFASL) and soluble forms (sFAS and sFASL), has been related to apoptosis driven by chemotherapy administration. In vitro experiments show chemotherapy upregulating membrane-bound forms, leading to an increase of receptor availability (at 24–72 h) and favoring apoptosis. The regulatory effect of chemotherapy on sFAS in patients has never been explored prospectively in advanced colorectal cancer (ACRC). We performed a pharmacodynamic study to address sFAS/sFASL variation. A prospective phase II translational multicenter study was designed to evaluate progression-free rate (PFR) in patients with ACRC treated with irinotecan and cetuximab in third-line therapy. The effect of sFAS was studied in vitro in colorectal cancer cell lines. Our results showed that statistically significant changes were observed in sFAS at 24–72 h compared to baseline levels in the pharmacodynamic study. Of the 93 patients enrolled in the prospective study in third-line therapy with cetuximab–irinotecan, 85 were evaluated for sFAS/sFASL changes at 48 h. There was no difference in PFR at 4 months between patients with sFAS and sFASL changes. In vitro analysis showed that although LoVo cell lines were sensitive to oxaliplatin and fluorouracil due to modulation of sFAS and FAS, HT29 lines were not. In summary, chemotherapy regulates FAS soluble fractions in vitro and in vivo, but does not predict PFR in ACRC patients undergoing third-line therapy with the combination of cetuximab and irinotecan.

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Acknowledgments

This work was supported by CIBEREHD that is funded by the Instituto de Salud Carlos III.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Medical Oncology Department, Hospital Clínic Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Catalonia, Spain

    Jordi Codony-Servat, Xabier Garcia-Albeniz, Rosa Gallego & Joan Maurel

  2. Medical Oncology Department, Hospital Parc Taulí, Sabadell, Spain

    Carles Pericay

  3. Medical Oncology Department, Hospital Miguel Servet, Zaragoza, Spain

    Vicente Alonso

  4. Medical Oncology Department, Hospital Clínico, Zaragoza, Spain

    Pilar Escudero

  5. Medical Oncology Department, Instituto Valenciano de Oncología (IVO), Valencia, Spain

    Carlos Fernández-Martos

  6. Medical Oncology Service, Fundació Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Spain

    Anna Martínez-Cardús

  7. Medical Oncology Department, Hospital Clínic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Villarroel 170, 08036, Barcelona, Catalonia, Spain

    Jordi Codony-Servat & Joan Maurel

  8. Medical Oncology Service, Institut Català d’Oncologia-Hospital Germans Trias i Pujol, Badalona, Spain

    Eva Martinez-Balibrea

Authors
  1. Jordi Codony-Servat
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  2. Xabier Garcia-Albeniz
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  3. Carles Pericay
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  4. Vicente Alonso
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  6. Carlos Fernández-Martos
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  7. Rosa Gallego
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  8. Anna Martínez-Cardús
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  9. Eva Martinez-Balibrea
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  10. Joan Maurel
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Corresponding authors

Correspondence to Jordi Codony-Servat or Joan Maurel.

Additional information

Jordi Codony-Servat and Xabier Garcia-Albeniz contributed equally to this work.

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12032_2012_428_MOESM1_ESM.tif

Supplementary Figure. Overall survival according to sFAS/sFASL ratio (A) and sFAS (B) increasing after 48 h of chemotherapy initiation. There was no difference between groups in overall survival (OS) (TIFF 127 kb)

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Codony-Servat, J., Garcia-Albeniz, X., Pericay, C. et al. Soluble FAS in the prediction of benefit from cetuximab and irinotecan for patients with advanced colorectal cancer. Med Oncol 30, 428 (2013). https://doi.org/10.1007/s12032-012-0428-0

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  • DOI: https://doi.org/10.1007/s12032-012-0428-0

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