Preemptive Versus Reactive Topical Clobetasol for Regorafenib-Induced Hand-Foot Reactions: A Preplanned Analysis of the ReDOS Trial

Abstract

Background Hand‐foot skin reaction (HFSR) is the most common regorafenib‐induced adverse event and is in need of effective prevention and palliation. Materials and Methods The Regorafenib Dose Optimization Study (ReDOS), a four‐arm, previously published trial with a 1:1:1:1 randomization scheme, was analyzed in a manner in keeping with the original protocol to assess whether clobetasol 0.05% cream (a corticosteroid) applied to the palms and soles twice per day for 8 weeks was more effective when prescribed preemptively (before the development of HFSR) versus reactively (after the development of HFSR). Patients were assessed during the first two cycles of regorafenib. Results Sixty‐one patients received preemptive clobetasol, and 55 received reactive clobetasol. Groups were balanced on demographics. Over the first two cycles, no evidence of HFSR occurred in 30% with preemptive clobetasol versus 13% with reactive clobetasol (p = .03). During the first cycle, 54% and 45% of patients had no HFSR with preemptive and reactive clobetasol, respectively (p = .35). During the second cycle, 33% and 15% had no HFSR with preemptive and reactive clobetasol, respectively (p = .02). During the second cycle, rates of grade 1, 2, and 3 HFSR were 30%, 8%, and 3%, respectively, with preemptive clobetasol and 43%, 18%, and 7%, respectively, with reactive clobetasol (p = .12). Patient‐reported outcomes showed HFSR compromised nearly all activities of daily living with worse quality of life in patients who received reactive versus preemptive clobetasol. No clobetasol‐induced adverse events were reported. Conclusion Preemptive clobetasol might lessen regorafenib‐induced hand‐foot reactions compared with reactive therapy. Further confirmatory studies are needed in a larger patient cohort. Implications for Practice Regorafenib causes hand‐foot skin reactions. Preemptive clobetasol, a high‐potency topical corticosteroid, appears to lessen the severity of this adverse event. Although further study is needed, the favorable adverse event profile of this intervention might prompt clinicians to discuss this option with their patients.

Topical interventions for preventing hand-foot syndrome resulting from antineoplastic therapy: A scoping review

“…The results brought by another study ( 33 ) included in this review demonstrated that preventive therapy with clobetasol, a high-potency topical corticosteroid, is associated with lower rates of regorafenib-induced HFS. During the second cycle of regorafenib, the frequency of HFS was 30% for grade 1, 8% for grade 2, and 3% for grade 3, with the use of preventive clobetasol.…”

“…The use of topical corticosteroids was mapped in seven studies ( 3 , 33 , 40 , 44 , 51 , 57 , 61 ) . Among them, the use of clobetasol cream at 0.05% ( 33 ) and topical steroids associated with dexpanthenol ( 57 ) was observed.…”

“…The use of topical corticosteroids was mapped in seven studies ( 3 , 33 , 40 , 44 , 51 , 57 , 61 ) . Among them, the use of clobetasol cream at 0.05% ( 33 ) and topical steroids associated with dexpanthenol ( 57 ) was observed. The other studies did not inform the type of topical corticosteroid or its concentration ( 3 , 40 , 44 , 51 , 62 ) .…”

“…The publication period of the studies ranged from 2004 to 2023, being more concentrated in 2022 (n = 7) (12,(27)(28)(29)(30)(31)(32) . Ten studies were carried out in the United States of America (n = 10) (3,33,47,50,(58)(59)(60)(61)(62)(63) . Regarding the design, twenty studies were randomized clinical trials (RCT) (n = 20) (27,28,(31)(32)(33)(34)(35)(36)(37)(38)(42)(43)(44)46,48,(52)(53)(54)58) .…”

“…Ten studies were carried out in the United States of America (n = 10) (3,33,47,50,(58)(59)(60)(61)(62)(63) . Regarding the design, twenty studies were randomized clinical trials (RCT) (n = 20) (27,28,(31)(32)(33)(34)(35)(36)(37)(38)(42)(43)(44)46,48,(52)(53)(54)58) . The scales used by the RCT to classify HFS were the Common Terminology Criteria for Adverse Events (CTCAE) (n = 17) (3,12,13,15,27,(32)(33)(34)36,37,41,43,(52)(53)(54)58) ; World Health Organization Hand-Foot Syndrome Rating Scale (WHO HFS) (n = 6) (28,29,31,35,…”