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New insights into renal toxicity of the B-RAF inhibitor, vemurafenib, in patients with metastatic melanoma

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Abstract

Purpose

Vemurafenib (VMF) is a B-RAF inhibitor used in the treatment of B-RAF-V600-mutant metastatic melanomas. Reports of acute kidney injury (AKI) in patients treated with VMF are scarce.

Methods

To investigate the incidence and severity of AKI, we conducted a retrospective, observational, monocentric study in the Lyon Sud Hospital University, France, which included 74 patients with metastatic B-RAF-mutated melanomas treated with VMF, between June 2011 and August 2014. According to the Kidney Disease Improving Global Outcomes Guidelines, AKI is defined as an increase in serum creatinine concentration exceeding the baseline concentration by 1.5 fold. Serum creatinine was thus determined before treatment, on a monthly basis during treatment, and 3 months after treatment discontinuation. Patients were divided into two main groups: AKI-positive (AKI+) and AKI-negative (AKI−) and further subdivided into three groups according to AKI severity (stage 1, 2 or 3). To visualize the tissue damage caused by VMF, kidney biopsies were performed for two stage 1 AKI+ patients.

Results

Of the 74 patients, 30 (40.5 %) were AKI−, and of the 44 AKI+ patients (59.5 %), 29 (66 %) were diagnosed within the first three months of treatment. There were significantly more men in the AKI+ group: n = 33 (75 %) versus n = 12 (40 %) women, p = 0.004 with an odds ratio for developing AKI of 4.6 (95 % CI 1.48–14.23). Most AKI + cases were considered as stage 1 (n = 40; 91 %) and the remaining four (9 %) as stage 2 AKI. Kidney biopsies revealed interstitial fibrosis and acute focal tubular damage. However, renal failure was reversible in 80 % of patients within 3 months of VMF discontinuation.

Conclusions

We observed frequent, reversible, moderately severe AKI with some histological evidence of tubular and interstitial damage in VMF-treated patients, suggesting that renal function should be carefully monitored in male patients, especially during the first 3 months.

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Acknowledgments

The authors would like to thank the members of Dermatology Department of the CHU Lyon Sud, and Pierre Trolliet MD, Anne-Cécile Rouveure MD, Abbas Deeb MD from the Nephrology Department of CHU Lyon Sud, Lyon, France, for the help with patient recruitment. They would also like to acknowledge editorial assistance by Margaret Haugh (MediCom Consult, Villeurbanne, France) funded by ADEPHAR and Brigitte Manship (Cancer Research Center of Lyon).

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Authors and Affiliations

  1. Department of Nephrology, Centre Hospitalier Lyon Sud, 165, Chemin du Grand Revoyet, 69495, Pierre Bénite, France

    Cécile Teuma, Solenne Pelletier, Mathilde Nouvier, Frédérique Dijoud, Denis Fouque & Maurice Laville

  2. Department of Dermatology, Centre Hospitalier Lyon Sud, 69495, Pierre Bénite, France

    Marie Perier-Muzet, Mona Amini-Adl, Gérard Duru, Luc Thomas & Stéphane Dalle

  3. UCBL, INSERM, Université de Lyon, Lyon, France

    Cécile Teuma, Solenne Pelletier, Mathilde Nouvier, Denis Fouque & Maurice Laville

  4. Centre de Recherche en Cancérologie de Lyon, Lyon, France

    Marie Perier-Muzet, Mona Amini-Adl, Gérard Duru, Luc Thomas & Stéphane Dalle

Authors
  1. Cécile Teuma
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  2. Marie Perier-Muzet
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  3. Solenne Pelletier
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  4. Mathilde Nouvier
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  6. Frédérique Dijoud
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  7. Gérard Duru
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  8. Luc Thomas
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  9. Denis Fouque
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  10. Maurice Laville
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  11. Stéphane Dalle
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Correspondence to Cécile Teuma.

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Teuma, C., Perier-Muzet, M., Pelletier, S. et al. New insights into renal toxicity of the B-RAF inhibitor, vemurafenib, in patients with metastatic melanoma. Cancer Chemother Pharmacol 78, 419–426 (2016). https://doi.org/10.1007/s00280-016-3086-7

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  • DOI: https://doi.org/10.1007/s00280-016-3086-7

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