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Pazopanib with low fat meal (PALM) in advanced renal cell carcinoma

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Summary

Background Pazopanib is approved for metastatic renal cell carcinoma (RCC). We assessed the safety and efficacy of pazopanib with a low fat meal (LFM): <400 cal and < 20% fat or 10 g per meal. Methods A single arm study of pazopanib with a LFM in 16 adult patients with metastatic RCC with a clear cell component, RECIST 1.1 measurable disease, ECOG PS ≤ 2, and ≤ 3 prior therapies. Pazopanib at 400 mg daily given with LFM for 12 weeks. Incremental dose increases up to 800 mg, or irreversible decreases to 200 mg, allowed every 2 weeks. Primary study endpoint was safety; adverse events (AE) measured per CTCAE version 4.0. Secondary endpoints of RECIST 1.1 response with assessment as 12 weeks; pharmacokinetic (PK) analysis at nine time points, and CYP3A4 polymorphism evaluation. Results Pazopanib with a LFM was well tolerated; 13 of 16 subjects completed all 12 weeks. Three patients withdrew due to adverse events (AEs), with five occurrences of grade 3 AEs. Conclusions Pazopanib with a LFM has acceptable safety and comparable efficacy to fasting administration. Total median pazopanib dose per subject for the study duration was 63.5% of maximum possible conventional dose. A larger study is warranted. Clinical Trial Registration Number: NCT02729194.

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Acknowledgements

We gratefully acknowledge the participation of our patients and their families as well the efforts of the University of Michigan Rogel Cancer Center Dieticians Melissa Shannon-Hagan and Nancy Burke, who counseled patients regarding low-fat meals for this study.

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Authors and Affiliations

  1. Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan, Ann Arbor, MI, USA

    Melissa A. Reimers & Christina Gersch

  2. Swedish Medical Center, Swedish Cancer Institute, Seattle, WA, USA

    Maryann M. Shango

  3. Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA

    Stephanie Daignault-Newton

  4. College of Literature, Arts and Sciences, University of Michigan, Ann Arbor, MI, USA

    Rachel Dedinsky

  5. Rogel Cancer Center, University of Michigan Health System, Ann Arbor, MI, USA

    Danielle Karsies

  6. College of Pharmacy, University of Michigan, Ann Arbor, MI, USA

    Shawna Kraft, Jeremy A. Felton & Bo Wen

  7. University of Michigan Medical School, University of Michigan, Ann Arbor, MI, USA

    Liam Riddle

  8. Department of Internal Medicine, Division of Hematology/Oncology, Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA

    James M. Rae

  9. Department of Internal Medicine, Division of Hematology/Oncology, Ann Arbor, MI, USA

    Bruce G. Redman & Ajjai S. Alva

Authors
  1. Melissa A. Reimers
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  2. Maryann M. Shango
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  3. Stephanie Daignault-Newton
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  4. Rachel Dedinsky
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  6. Shawna Kraft
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  7. Liam Riddle
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  8. Jeremy A. Felton
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  9. Bo Wen
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  10. Christina Gersch
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  11. James M. Rae
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  12. Bruce G. Redman
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  13. Ajjai S. Alva
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Contributions

M.A.R. and A.S.A. analyzed and interpreted the data and wrote the manuscript. A.S.A, M.M.S. and B.G. R. designed the study and enrolled patients. S.D.N. conducted statistical analysis. R.D. and L.R. collected patient information. J. A. F. and B.W. conducted pharmacokinetic analysis. S.K. provided clinical pharmacy support. C.G. and J.R. conducted pharmacogenomic analysis. D.K. provided nutrition information and counseled patients.

Corresponding author

Correspondence to Melissa A. Reimers.

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Ethical approval

Informed consent was obtained from all individual participants included in the study. 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. This article does not contain any studies with animals performed by any of the authors.

Conflict of interest

The authors declare no potential conflicts of interest.

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Reimers, M.A., Shango, M.M., Daignault-Newton, S. et al. Pazopanib with low fat meal (PALM) in advanced renal cell carcinoma. Invest New Drugs 37, 323–330 (2019). https://doi.org/10.1007/s10637-018-0692-8

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  • DOI: https://doi.org/10.1007/s10637-018-0692-8

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