Résumé
Purpose: Only a minority of patients with early breast cancer (EBC) treated with adjuvant or neoadjuvant chemotherapy have sufficient baseline vitamin D. The current recommendations regarding daily vitamin D supplementation appears too low to correct this deficiency in this population. Optimal vitamin D dosing has yet to be determined in this setting. The current randomized phase III study address the issue of the effectiveness and safety of a tailored high dose oral vitamin D supplementation as a means for restoring normal 25-hydroxy vitamin D (25OHD) levels in a large population of chemotherapy-treated EBC patients.
Methods: Chemotherapy-treated EBC patients were stratified according to the degree of Vitamin D deficiency, time between chemotherapy initiation and inclusion (0 to 6 months versus 6 to 12 months), hormone receptors status and menopausal status. Participants were randomly assigned to receive a 6-months conventional (C) vitamin D and calcium supplementation or a 6-months high dose oral vitamin D regimen tailored on the degree of deficiency (T) associated with a conventional calcium supplementation. Primary endpoint was the efficacy (6-months percentage of 25OHD serum levels normalization) in the T arm compared with the C arm. Patients without vitamin D normalization from the C arm were allowed to switch to the T arm after 6 months. Statistical analyses were performed on an intent to treat basis.
Results: The trial accrued 215 patients, among which 197 patients presented with vitamin D deficiency, and randomized 195 patients (T, 100; C, 95) from July 2011 to January 2013. The groups were well balanced in regard to the stratification characteristics, as well as in regard of median weight and neoadjuvant or adjuvant chemotherapy status. Compliance to the daily oral supplementation was low in both arms, 64% of the patients in both arms taking less than 80% of the planned oral supplementation dose. Compliance to the tailored high dose vitamin D schedule appeared better (78%). After 6 months of treatment, at the primary endpoint analysis time, significantly more patients in the T arm presented with normalized serum vitamin D levels compared to the C arm (30% vs. 12.6%; p=0.003). Vitamino-calcic supplementation was well tolerated, with no difference in the treatment-related toxicity between the 2 arms. 52 patients without vitamin D normalization from the C arm switched to the T arm after 6 months. At the 12 months endpoint, 44% of these patients achieved vitamin D normalization.
Conclusion: In this randomized phase III study, a tailored high dose oral vitamin D supplementation allowed a statistically higher percentage of serum 25OHD levels normalization compared to a conventional regimen, without any increase in side effects, in a large population of chemotherapy-treated EBC patients. Observance of a daily oral supplementation remains poor in this setting, advocating for an adaptation of the schedule and dosage of this supplementation in a population of patients subject to chemotherapy-induced emesis.
Clinical trial number NCT01480869.
Citation Format: William Jacot, Nelly Firmin, Lise Roca, Delphine Topart, Sophie Gallet, Anna Durigova, Simone Mirr, Stéphane Pouderoux, Jean-Pierre Bleuse, Pierre-Jean Lamy, Gilles Romieu. Final results of the VitaCal randomized phase III study evaluating the impact of a tailored oral vitamin D supplementation regimen on serum 25-hydroxyvitamin D levels in early breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-21-02.