Safety and Efficacy of Bis-Glyceryl Ascorbate as Prophylaxis for Hand-Foot Skin Reaction: A Single-Arm, Open-Label Phase I/II Study (DGA Study)

Abstract

Background Hand-foot skin reaction (HFSR) induced by multiple tyrosine kinase inhibitors (TKIs) is a serious side effect that can cause treatment interruption or decreased dosing. This study was conducted to evaluate the safety and efficacy of bis-glyceryl ascorbate (Amitose bis(di)-glyceryl ascorbate [DGA])-containing cream (DGA cream) for the prevention of sunitinib-induced HFSR. Methods A single-arm, open-label phase I/II study was conducted, targeting patients with metastatic renal cell carcinoma (mRCC) who were receiving sunitinib therapy with a schedule of 2 weeks on/1 week off. The participants applied DGA cream to both palmar and plantar surfaces in combination with a moisturizing agent as standard-of-care prophylaxis during two sunitinib treatment cycles (6 weeks). The primary endpoint in phase I was safety defined as dermatological abnormalities and it was determined in the first five participants. The primary endpoint in phase II was efficacy defined as development of grade 1 or higher HFSR defined by Common Terminology Criteria for Adverse Events within 6 weeks and it was determined on a full analysis set (FAS) defined as the population including all participants who used DGA cream once in the study duration. Efficacy in the per protocol set (PPS) defined as the population excluding seven patients whose study treatment was interrupted was evaluated as a secondary endpoint. Results Twenty-four patients were enrolled as a FAS. No dermatological abnormalities occurred in the first 5 patients enrolled in the phase I study. Three patients developed HFSR (grade 1: n = 2, grade 2: n = 1) in the observation period. The HFSR incidence rate was 12.5% (3/24; 95% confidence interval [CI]: 2.7%-32.4%) in the FAS, which was significantly lower than the incidence rate predefined as a threshold of 33.3% by a previous report from our hospital (P = .030). The incidence rate in the 17 patients of the PPS was 17.6% (3/17; 95%CI: 3.8%-43.4%). Conclusion DGA cream may be safe and effective in the prophylaxis of HFSR in mRCC patients who receive sunitinib therapy (Trial ID: jRCTs051180051).

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

“…Some studies did not mention the scale used (n = 5) ( 14 , 30 , 38 , 44 , 46 ) . Only 4 studies specified the Degree ≤2 of the HFS as inclusion criteria ( 27 , 34 , 37 , 52 ) in their methodology.…”

“…Other topical interventions were mapped, such as hydrocolloid dressing containing ceramide ( 3 . 45 ) ; topical neurotropin ( 14 ) ; bis-glyceryl ascorbate ( 27 ) ; topical heparin ( 32 . 50 ) ; 1% topical pyridoxine (vitamin B6) ( 11 ) ; hyaluronic acid ( 49 ) ; topical lanolin ( 49 ) ; isolated topical ( 49 , 57 ) uridine, or uridine associated with 10% thymine ( 49 ) ; hydrocolloid dressing ( 52 ) ; topical DMSO (dimethyl sulfoxide) ( 49 , 55 , 63 ) ; vaseline ( 56 ) ; topical eniluracil ( 57 ) ; as well as the use of UV A and B sunscreen (Blue Lizard ® ) ( 60 ) .…”

“…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) .…”

“…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,…”

The Efficacy and Safety of the Shouzu Ning Decoction Treatment Versus Halometasone Plus Celecoxib Treatment in Patients With Grade 2 HFSR: A Randomized Clinical Trial

“…Furthermore, SIRT1 inhibitor nicotinamide was found to be effective in treating sorafenib-induced HFSR, 27 but with low case numbers, which needed to be further investigated. In addition, a number of randomized controlled studies evaluated that prophylactic strategies using 1% bis-glyceryl ascorbate cream, 28 urea-based cream, 8 , 29 or hydrocolloid dressing containing ceramide could decrease the incidence of HFSR. 30 Despite advances in prophylactic management, a significant number of patients progressed to grade 2 HFSR, leading to modification of MKIs dosage.…”