Prevention and palliation of hand-foot skin reaction (HSFR) due to the multikinase inhibitors (MKIs): An evidence-based assessment of the published peer-reviewed literature

Abstract

20588 Background: Significant advances in cancer outcomes with MKIs have resulted in cutaneous side effects such as HFSR. While HFSR symptoms are usually mild, affecting up to 30% of pts treated newer oral agents, HFSR may impair QoL and limit cancer treatment duration or intensity. Understanding the existing evidence for prevention and palliation of HFSR to generate appropriate clinical trial design and develop evidence-based prevention and palliation guidelines is important. Methods: Sixteen separate searches of the NLM PubMed database were conducted using search terms and combination of terms relevant to anticancer therapies and HFSR. Supplemental searches were performed on the Cochrane Reviews, BIOSIS, CancerLit and ASCO website. Articles were categorized as 1: (MKI + HFSR), 2: (MKI + other skin toxicity), 3: (other antineoplastic agents + HFSR) and 4: (other). The primary focus was on Category 1 articles reporting on HFSR treatment efficacy and patient outcome. Two reviewers independently reviewed and coded all titles and/or abstracts. Results: The searches yielded 2057 articles of which 338 (16%) met inclusion criteria for codes 1–4. 44 (13%) of these were Category 1 pertaining to MKIs with details of HFSR histology, pathogenesis, clinical outcome, QoL impact, and/or prevention and treatment approaches; 270 (80%) were Category 3 pertaining to other antineoplastic agents with details of those above. No Category 1 or 3 articles on prevention/palliation approaches to HFSR were randomized controlled trials. Approaches were classified as anecdotal or case reports, and included measures such as dose reductions, pedicures and sandals during anticancer therapy. Systemic/local strategies were presented, including pyridoxine, urea-based creams and corticosteroids. 1 article presented a meta analysis of 4 phase I sorafenib dose-escalation trials and showed a preliminary correlation of ≥ grade 2 skin toxicity/diarrhea with a significantly longer TTP. Conclusions: The literature does not include empirical evidence for optimal prevention or palliation of HFSR to MKIs. Evidence-based palliative approaches to skin toxicities from MKIs are clearly needed. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer Bayer Bayer Bayer Bayer