A Randomized, double-blind, placebo-controlled trial evaluating the effect of topical urea for secondary prophylaxis of hand foot skin reaction in renal cell cancer patients on sunitinib therapy

Abstract

Introduction

Hand foot skin reaction (HFSR) is a common dose-limiting adverse effect of multi kinase inhibitors (MKI) whose mechanism is not fully understood, and the prophylaxis is inadequate.

Objective

In this pilot study, a double-blind, randomized placebo-controlled trial was conducted to evaluate the effect of topical urea in secondary prevention of sunitinib-induced HFSR in renal cell cancer patients.

Methods

Out of 55 screened patients, 14 were randomized to receive topical urea or placebo for four weeks. The association of HFSR with drug levels of sunitinib and its metabolite (n-desethyl sunitinib), genetic polymorphism of VEGFR2 gene, quality of life (QOL) and biochemical markers was also assessed.

Results

The results showed that urea-based cream was not superior to placebo (p = 0.075). There was no change in the QOL in both the groups. Single nucleotide polymorphism was checked for two nucleotides rs1870377 and rs2305948 located in VEGFR2 gene on chromosome 4. SNP (variant T>A) at rs1870377 was associated with appearance of new HFSR as compared to the wild type, although the association was not statistically significant (OR 0.714). There was no statistically significant difference between mean plasma levels of sunitinib and N-desethyl sunitinib in urea arm as comparted to placebo arm as compared to placebo. The best fit population pharmacokinetic model for sunitinib was one compartment model with first order absorption and linear elimination. The median (IQR) of population parameters calculated from the population pharmacokinetics model for Ka, V and Cl was 0.22 (0.21-0.24) h-1, 4.4 (4.09-4.47) L, 0.049 (0.042-0.12) L/hr, respectively.

Conclusion

The study suggested that the urea-based cream was not superior to placebo in decreasing the appearance of new HFSR in renal cancer patients receiving 4:2 regimen of sunitinib.