title: Treatment of palmar-plantar erythrodysesthesia (PPE) with topical sildenafil: a pilot study.
abstract: OBJECTIVE
  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.
authors.affiliation: Duke Cancer Institute, Seeley G. Mudd Bldg., 10 Bryan Searle Drive, Box 3052, Durham, NC, 27710, USA.
authors.forename: Kellen L
authors.initials: KL
authors.lastname: Meadows
authors.forename: Christel
authors.initials: C
authors.lastname: Rushing
authors.forename: Wanda
authors.initials: W
authors.lastname: Honeycutt
authors.forename: Kenneth
authors.initials: K
authors.lastname: Latta
authors.forename: Leigh
authors.initials: L
authors.lastname: Howard
authors.forename: Christy A
authors.initials: CA
authors.lastname: Arrowood
authors.forename: Donna
authors.initials: D
authors.lastname: Niedzwiecki
authors.forename: Herbert I
authors.initials: HI
authors.lastname: Hurwitz
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000069287:Capecitabine; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D060831:Hand-Foot Syndrome / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D010865:Pilot Projects; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010919:Placebos / Q000008:administration & dosage; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011687:Purines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use; D000068677:Sildenafil Citrate; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077210:Sunitinib; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D010879:Piperazines; D010919:Placebos; D047428:Protein Kinase Inhibitors; D011687:Purines; D011758:Pyrroles; D013449:Sulfonamides; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D003841:Deoxycytidine; D000069287:Capecitabine; D000068677:Sildenafil Citrate; D005472:Fluorouracil; D000077210:Sunitinib