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Treatment of palmar-plantar erythrodysesthesia (PPE) with topical sildenafil: a pilot study

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Abstract

Purpose

Palmar-plantar erythrodysesthesia (PPE) is a common chemotherapy and anti-VEGF multi-kinase inhibitor class-related toxicity that often results in debilitating skin changes and often limits the use of active anti-cancer regimens. Mechanistic and anecdotal clinical evidence suggested that topical application of sildenafil cream may help reduce the severity of PPE. Therefore, we conducted a randomized, double-blind, placebo-controlled pilot study to evaluate the feasibility, safety and efficacy of topical sildenafil cream for the treatment of PPE.

Methods

Eligible subjects were required to have grade 1–3 PPE associated with either capecitabine or sunitinib. Subjects were randomized to receive 1 % topical sildenafil cream to the left extremities or right extremities and placebo cream on the opposite extremity. Two times per day, 0.5 mL of cream was applied to each affected hand/foot. The primary endpoint was improvement in PPE grading at any point on study. Clinical assessments were evaluated by NCI-CTC 4.0 grading and patient self-reported pain.

Results

Ten subjects were enrolled, nine were evaluable for safety and efficacy. Five of nine subjects reported some improvement in foot pain and three of eight subjects for hand pain improvement. One of these subjects noted specific improvement in tactile function. No treatment-related toxicities were observed.

Conclusions

In this limited, single-center study, topical cream containing 1 % sildenafil is feasible to administer, is well-tolerated, and may mitigate PPE-related symptoms due to anti-cancer therapeutic agents. Further validation is necessary.

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Acknowledgments

We gratefully acknowledge the invaluable contributions of the patients and their families. We specifically acknowledge the contribution of Neal Kaplan and Drs. Bruce Burnett and Erin O’Reilly of Duke Translational Medicine Institute regulatory who provided guidance and support with the preparation of the IND application and the fund in part by the Duke University’s CTSA Grant 1 UL1 RR024128 from NCRR/NIH. This research was supported by the National Institute of Health Grant 5K24-CA113755-05 (H Hurwitz).

Conflict of interest

The authors have no financial conflicts of interest to disclose and have full control of all primary data. The authors agree to allow the journal to review the data if requested.

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Authors and Affiliations

  1. Duke Cancer Institute, Seeley G. Mudd Bldg., 10 Bryan Searle Drive, Box 3052, Durham, NC, 27710, USA

    Kellen L. Meadows, Wanda Honeycutt, Leigh Howard, Christy A. Arrowood & Herbert I. Hurwitz

  2. Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC, 27705, USA

    Christel Rushing & Donna Niedzwiecki

  3. Duke Compounding Facility, Duke University Hospital, Durham, NC, 27710, USA

    Kenneth Latta

  4. Duke Cancer Network, Durham, NC, 27707, USA

    Christy A. Arrowood

  5. Gates Healthcare Associates Inc, Middleton, MA, 01949, USA

    Kenneth Latta

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  1. Kellen L. Meadows
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Correspondence to Herbert I. Hurwitz.

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Meadows, K.L., Rushing, C., Honeycutt, W. et al. Treatment of palmar-plantar erythrodysesthesia (PPE) with topical sildenafil: a pilot study. Support Care Cancer 23, 1311–1319 (2015). https://doi.org/10.1007/s00520-014-2465-z

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  • DOI: https://doi.org/10.1007/s00520-014-2465-z

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