Abstract P3-14-01: High-dose vitamin D supplementation for the correction of vitamin D insufficiency in patients undergoing adjuvant chemotherapy for breast cancer, a phase II multicenter study
Authors: Jacot W , D'Hondt V , Touraine C , Chapelle A , Legouffe E , Metge M , Rifai L , Roca L , Pouderoux S , Romieu G 
Published: May 2019

Abstract
Background:Vitamin D (VitD) insufficiency affects most of patients with early breast cancer (EBC). Breast cancer treatment may lead to bone loss, due to premature ovarian failure or direct chemotherapy (CT) cytotoxic effects. These increase the risk of skeletal morbidity as compared to women without breast cancer history. We previously published the persistence of VitD insufficiency at the end of adjuvant CT despite an adapted dose supplementation. We report here the safety and efficacy analysis of a phase II trial evaluating a high-dose oral VitD supplementation regimen for correction of VitD insufficiency in insufficient EBC patients treated with adjuvant CT.
Material and methods: EBC patients with VitD insufficiency for whom adjuvant CT was planned were eligible for this study. They received one dose of 100,000 IU 25OH-vitamin D every 3 weeks from day 1 of cycle 1 to day 1 of cycle 5, except in case of clinical or biological adverse event related to vitamin D and calcium metabolism, leading to early discontinuation. The primary endpoint was the percentage of serum 25OH-vitamin D level normalization at day 1 of cycle 6 (D1C6). Secondary endpoints were the safety, the Vitamin D and calcium parameters (blood calcium, phosphorus and parathormone [PTH] levels, urinary calcium excretion) at baseline and the description of their evolution during adjuvant CT, as well as the evaluation of the predictive value of these biomarkers and baseline clinical factors on the percentage of VitD normalization at D1C6.
Results: Among 45 eligible patients, 44 were evaluable for the primary endpoint. Among them, 21 (47.7%; 95%CI: 33.0-62.8) achieved a 25OH-Vitamin D correction at D1C6. No clinical toxicity linked to the VitD treatment was reported. However, 13 patients (29.5%) presented an asymptomatic grade 1 hypercalciuria, possibly linked to the VitD treatment, without concomitant change in the kidney function, but which lead to the interruption of the high dose oral VitD supplementation in 10 of the 13 patients. VitD normalization rates at 6, 12, 18 and 24 months were 50, 28.9, 80 and 60.9%, respectively. No clinical or biological marker was found to significantly predict the 6-month 25OH vitamin D normalization.
Conclusions: A high-dose 25OH-vitamin D regimen allowed a high percentage of serum 25OHD level normalization at D1C6 in EBC patients undergoing adjuvant CT. An asymptomatic increase in urinary calcium excretion was observed in one third of the patients, without clinical consequences. The physiopathology of this urinary calcium increase warrants further evaluation, since it is a classical reason for VitD treatment interruption, leading to a lower rate of correction in this highly requiring clinical setting.
Citation Format: Jacot W, D'Hondt V, Touraine C, Chapelle A, Legouffe E, Metge M, Rifai L, Roca L, Pouderoux S, Romieu G. High-dose vitamin D supplementation for the correction of vitamin D insufficiency in patients undergoing adjuvant chemotherapy for breast cancer, a phase II multicenter study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-14-01.