Ng K, et al. - Among 139 patients with advanced or metastatic colorectal cancer (CRC), researchers determined whether high-dose vitamin D₃ added to standard chemotherapy improves outcomes. According to this double-blind phase 2 randomized clinical trial, among patients with metastatic CRC, the addition of high-dose vitamin D₃ vs standard-dose vitamin D₃ to standard chemotherapy resulted in a difference in median progression-free survival (PFS) which was not statistically significant but with a significantly improved supportive hazard ratio.

Methods

• This trial of 139 subjects with advanced or metastatic CRC conducted at 11 US academic and community cancer centers from March 2012 through November 2016 (database lock: September 2018).
• Interventions included mFOLFOX6 plus bevacizumab chemotherapy every 2 weeks and either high-dose vitamin D₃(n = 69) or standard-dose vitamin D₃ (n = 70) daily until disease progression, intolerable toxicity, or withdrawal of consent.
• PFS evaluated by the log-rank test and a supportive Cox proportional hazards model was the primary end point.
• Testing has been 1-sided.
• Tumor objective response rate (ORR), overall survival (OS), and change in plasma 25(OH)D level were included secondary end points.

Results

• Of the 139 subjects (mean age, 56 years; 60 [43%] women) who completed or discontinued chemotherapy and vitamin D₃ (median follow-up, 22.9 months), the median PFS for high-dose vitamin D₃ was 13.0 months (95% CI, 10.1 to 14.7; 49 PFS events) vs 11.0 months (95% CI, 9.5 to 14.0; 62 PFS events) for standard-dose vitamin D₃ (log-rank P=.07); multivariable hazard ratio for PFS or death was 0.64 (1-sided 95% CI, 0 to 0.90; P=.02).
• No significant differences were found between high-dose and standard-dose vitamin D₃ for tumor ORR (58% vs 63%, respectively; difference, −5% [95% CI, −20% to 100%], P=.27) or OS (median, 24.3 months vs 24.3 months; log-rank P=.43).
• Investigators found that the median 25(OH)D level at baseline for high-dose vitamin D₃ was 16.1 ng/mL vs 18.7 ng/mL for standard-dose vitamin D₃ (difference, −2.6 ng/mL [95% CI, −6.6 to 1.4], P=.30); at first restaging, 32.0 ng/mL vs 18.7 ng/mL (difference, 12.8 ng/mL [95% CI, 9.0 to 16.6], P < .001); at second restaging, 35.2 ng/mL vs 18.5 ng/mL (difference, 16.7 ng/mL [95% CI, 10.9 to 22.5], P < .001); and at treatment discontinuation, 34.8 ng/mL vs 18.7 ng/mL (difference, 16.2 ng/mL [95% CI, 9.9 to 22.4], P < .001).
• Neutropenia (n = 24 [35%] vs n = 21 [31%], respectively) and hypertension (n = 9 [13%] vs n = 11 [16%]) were the most common grade 3 and higher adverse events for chemotherapy plus high-dose vs standard-dose vitamin D₃.