High-dose vitamin D supplementation does not improve outcome in a cutaneous melanoma population: results of a randomized double-blind placebo-controlled study (ViDMe trial).
De Smedt, Julie; Van Kelst, Sofie; Janssen, Laudineet al.
2024 • In British Journal of Dermatology, 191 (6), p. 886 - 896
High-dose vitamin D supplementation does not improve outcome in a cutaneous melanoma population results of a randomized double-blind placebo-controlled study (ViDMe trial).pdf
[en] [en] BACKGROUND: Observational studies in cutaneous melanoma (CM) have indicated an inverse relationship between levels of 25-hydroxyvitamin D and Breslow thickness, in addition to a protective effect of high 25-hydroxyvitamin D levels on clinical outcome.
OBJECTIVES: To evaluate whether high-dose vitamin D supplementation in curatively resected CM reduces melanoma relapse.
METHODS: In a prospective randomized double-blind placebo-controlled trial, 436 patients with resected CM stage IA to III (8th American Joint Committee on Cancer staging) were randomized. Among them, 218 received a placebo while 218 received monthly 100 000 IU cholecalciferol for a minimum of 6 months and a maximum of 42 months (treatment arm). Following randomization, patients were followed for a median of 52 months, with a maximum follow-up of 116 months. The primary endpoint was relapse-free survival. Secondary endpoints were melanoma-related mortality, overall survival, and the evolution of 25-hydroxyvitamin D serum levels over time.
RESULTS: In our population (mean age 55 years, 54% female sex) vitamin D supplementation increased 25-hydroxyvitamin D serum levels after 6 months of supplementation in the treatment arm by a median 17 ng mL-1 [95% confidence interval (CI) 9-26] compared with 0 ng mL-1 (95% CI 6-8) in the placebo arm (P < 0.001, Wilcoxon test) and remained at a steady state during the whole treatment period. The estimated event rate for relapse-free survival at 72 months after inclusion was 26.51% in the vitamin D supplemented arm (95% CI 19.37-35.64) vs. 20.70% (95% CI 14.26-29.52) in the placebo arm (hazard ratio 1.27, 95% CI 0.79-2.03; P = 0.32). After adjusting for confounding factors (including baseline stage, body mass index, age, sex and baseline season), the hazard ratio was 1.20 (95% CI 0.74-1.94, P = 0.46). The number of deaths from progression of CM and nonmelanoma-related deaths was similar in both the vitamin D supplemented and placebo groups (deaths from progression of CM, n = 10 and n = 11, respectively; nonmelanoma-related deaths, n = 3 and n = 2, respectively). No major adverse events were observed during the study.
CONCLUSIONS: In patients with CM, monthly high-dose vitamin D supplementation was safe, resulted in a sustained increase in 25-hydroxyvitamin D levels during the treatment period, but did not improve relapse-free survival, melanoma-related death or overall survival. [en] Cutaneous melanoma (CM) is the most lethal form of skin cancer. Previous studies have shown that low vitamin D (VD) levels in the blood at the time of CM diagnosis are associated with thicker tumours, and a worse outcome. The aim of this study was to examine whether monthly high-dose VD supplementation after diagnosis and surgical treatment of a primary melanoma could improve outcomes. We carried out a clinical trial that included 436 patients with CM who were randomly allocated into two groups. One group of 218 patients received a placebo (an inactive treatment) and another group of 218 patients received a monthly oral oil solution containing VD (known as the treatment group). We looked at relapse-free survival, levels of melanoma-related mortality, overall survival, and the evolution of VD levels over time, and compared the results for both groups. We found that monthly high-dose VD supplementation was safe, but did not protect against recurrence of CM or risk of death. Therefore, based on our study findings, we do not recommend high-dose VD supplementation for people with CM to improve melanoma outcomes.
Disciplines :
Dermatology
Author, co-author :
De Smedt, Julie; Laboratory of Dermatology, Department of Oncology, KU Leuven, UZ Leuven, Leuven, Belgium
Van Kelst, Sofie; Laboratory of Dermatology, Department of Oncology, KU Leuven, UZ Leuven, Leuven, Belgium
Janssen, Laudine; Laboratory of Dermatology, Department of Oncology, KU Leuven, UZ Leuven, Leuven, Belgium
Marasigan, Vivien; Department of Surgery, South Infirmary Victoria University Hospital, Cork, Ireland
Boecxstaens, Veerle; Oncological Surgery, Department of Oncology, KU Leuven, UZ Leuven, Leuven, Belgium
Bogaerts, Kris ; Leuven Biostatistics and Statistical Bioinformatics Centre (L-BioStat), KU Leuven, Leuven, Belgium
Belmans, Ann; Leuven Biostatistics and Statistical Bioinformatics Centre (L-BioStat), KU Leuven, Leuven, Belgium
Vanderschueren, Dirk; Clinical and Experimental Endocrinology, Department of Chronical Illness and Metabolism, KU Leuven, UZ Leuven, Leuven, Belgium
Vandenberghe, Katleen; Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium
Bechter, Oliver; Laboratory of Experimental Oncology (LEO), Department of Oncology, KU Leuven, UZ Leuven, Leuven, Belgium
Aura, Claudia; Conway Institute of Biomolecular and Biomedical Research, Pathology, University College Dublin, Ireland
Lambrechts, Diether; Laboratory for Translational Genetics, Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium
Strobbe, Tinne; Department of Dermatology, Imeldaziekenhuis, Bonheiden, Belgium
Emri, Gabriella; Department of Dermatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
Nikkels, Arjen ; Université de Liège - ULiège > Département des sciences cliniques > Dermatologie
Garmyn, Marjan; Laboratory of Dermatology, Department of Oncology, KU Leuven, UZ Leuven, Leuven, Belgium
High-dose vitamin D supplementation does not improve outcome in a cutaneous melanoma population: results of a randomized double-blind placebo-controlled study (ViDMe trial).
Kom op tegen Kanker VLAIO - Agentschap Innoveren & Ondernemen
Funding text :
This work was supported by Stand Up Against Cancer (Kom op tegen Kanker), Anticancer fund, grant number aA67 (Antikankerfonds), and FWO TBM (Applied Biomedical Reseach with a Primary Social Finality). Laboratoires SMB supplied the ampoules of D-cure and placebo.The authors wish to thank the study participants, Tine Vanhoutvin, Dorien Hunin and Julie Terrasson of the Department of Dermatology, KU Leuven, Joost Van den Oord, Sabrina D\u2019Haese and Kathleen Van den Eynde of the Department of Translational Cell and Tissue Research, KU Leuven and the Team of Precision Oncology Ireland for their contribution to the ViDMe study. This work was supported by Stand Up Against Cancer (Kom op tegen Kanker), Anticancer fund, grant number aA67 (Antikankerfonds), and FWO TBM (Applied Biomedical Reseach with a Primary Social Finality). Laboratoires SMB supplied the ampoules of D-cure and placebo.
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