Add-on high-dose vitamin D3 of little benefit in mCRC

Adding high-dose vitamin D3 to standard chemotherapy does not appear to improve outcomes in patients with previously untreated metastatic colorectal cancer (mCRC), as shown in a phase III trial.

The trial included 455 patients (median age 59 years, 40 percent female). These patients were randomly assigned to receive high-dose vitamin D3 (8,000 IU daily for 14 days as loading dose followed by 4,000 IU daily; n=228) or standard-dose vitamin D3 (400 IU daily; n=227) as an adjunct to mFOLFOX6 (modified FOLFOX6 [5-fluorouracil, leucovorin, oxaliplatin]) or FOLFIRI (5-fluorouracil, leucovorin, irinotecan) plus bevacizumab every 2 weeks. Vitamin D3 was given until disease progression, intolerable toxicity, or withdrawal of consent.

The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), overall survival (OS), and toxicity.

Over a median follow-up 20 months, the median PFS was 11.8 months in the high-dose vitamin D3 group vs 10.3 months in the standard-dose vitamin D3 group (p=0.25). No significant between-group difference was observed for ORR (51 percent vs 44 percent, respectively; p=0.12) or OS (median, 25.6 vs 27 months; p=0.66).

The incidence of common grade ≥3 adverse events was similar between the high- and standard-dose vitamin D3 groups, including neutropenia (32 percent vs 30 percent) and hypertension (20 percent vs 23 percent).