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Risks and benefits of phase I liver dysfunction studies: should patients with severe liver dysfunction be included in these trials?

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Summary

Introduction The goal of organ dysfunction Phase I trials is to characterize the safety and pharmacokinetics of novel agents in cancer patients with liver or kidney dysfunction, but the clinical benefit is not well established. Methods We reviewed 170 patients across 15 liver dysfunction studies at our institution, grouped based on the NCI-Organ Dysfunction Working Group criteria or Child-Pugh Score. Results The median survival for the entire cohort was two months and just one month amongst patients with severe liver dysfunction. Patients with normal or mild liver dysfunction, absence of tumor in liver, good performance status, higher serum albumin and lower bilirubin, aspartate transaminase and alkaline phosphatase had improved survival by univariate analysis. Serum albumin and liver function classification remained significant by multivariate analysis. Conclusion Given poor survival of patients with liver dysfunction, we need better criteria, such as albumin levels, for optimally selecting patients for liver dysfunction studies.

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Acknowledgements

We would like to thank all patients and their families for participating in the studies. We would also like to thank the office of regulatory affairs at CTRC their help with patient identification.

Disclaimer: This work has been presented in part at the ASCO 2014 Annual Meeting (abstract 2536).

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Authors and Affiliations

  1. University of Texas Health Science Center San Antonio, 7979 Wurzbach Rd, MC8026, San Antonio, TX, 78229, USA

    Christos Fountzilas, Selena Stuart, Brian Hernandez, Elizabeth Bowhay-Carnes, Joel Michalek, John Sarantopoulos, Anand Karnad, Sukeshi Patel, Steven Weitman & Devalingam Mahalingam

  2. Athens Naval and Veterans Hospital, 70 Dinokratous Str, 11521, Athens, Greece

    Christos Fountzilas

  3. Laredo Hematology & Oncology Associates, 1710 E. Saunders, Tower A, 1st floor, Laredo, TX, 78041, USA

    Selena Stuart

Authors
  1. Christos Fountzilas
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  2. Selena Stuart
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  3. Brian Hernandez
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  4. Elizabeth Bowhay-Carnes
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  8. Sukeshi Patel
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  10. Devalingam Mahalingam
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Correspondence to Devalingam Mahalingam.

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Funding

No funding was received for completion of this project. Christos Fountzilas is a recipient of a Cancer Research Training Award from the Cancer Prevention and Research Institute of Texas (RP140105). Sukeshi Patel has funding from P30AG044271. All authors are supported by the P30 Cancer Center Support Grant from the National Cancer Institute (CA054174).

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required.

Conflict of interest

The authors indicate no potential conflicts of interest.

Informed consent

All patients participated in clinical studies approved by the University of Texas Health Science Center at San Antonio Institutional Review Board. Individual consent was not required for this retrospective review.

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Fountzilas, C., Stuart, S., Hernandez, B. et al. Risks and benefits of phase I liver dysfunction studies: should patients with severe liver dysfunction be included in these trials?. Invest New Drugs 35, 386–391 (2017). https://doi.org/10.1007/s10637-017-0425-4

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  • DOI: https://doi.org/10.1007/s10637-017-0425-4

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