SUMMARY: The American Cancer Society estimates that approximately 133,000 new cases of colorectal cancer will be diagnosed in the United States in 2015 and close to 50,000 are expected to die of the disease. There is a growing body of evidence suggesting that Vitamin D has colon cancer preventing properties and may induce antitumor immunity. A recent study by Song and colleagues (Gut. 2015;64:260-271) showed that high plasma level 25-Hydroxy Vitamin D [25(OH)D] was associated with lower risk of colorectal cancer with intense immune reaction, supporting that vitamin D through tumor-host interaction may play a role in cancer immunoprevention. There appears to be a strong association between plasma 25(OH)D level and colorectal cancer (CRC) specific mortality, with better outcomes in patients with Stage I-III CRC, who had higher plasma levels of 25(OH)D (Zgaga L, et al. J Clin Oncol 2014;32:2430-2439). The researchers in this present study conducted a prospective analysis of data from CALGB 80405 trial and evaluated the relationship between plasma 25(OH)D level and patient outcomes, which included Overall Survival and Progression Free Survival (PFS). CALGB 80405 is a phase III trial in which patients with newly diagnosed, advanced colorectal cancer were initially randomized to three groups- 1) Chemotherapy (FOLFIRI or mFOLFOX6) with ERBITUX® (Cetuximab) 2) Chemotherapy with AVASTIN® (Bevacizumab) 3) Chemotherapy with ERBITUX® and AVASTIN®. The protocol was later amended to only include patients with KRAS Wild Type tumors and the chemotherapy with ERBITUX® and AVASTIN® group was deleted. This trial was not designed to compare chemotherapy regimens. The Overall Survival (OS) in both the treatment groups were similar at 29+ months.
In the present study, plasma 25(OH)D level were measured at baseline in 1,043 patients at the time of their enrollment in CALGB 80405, and dietary and lifestyle behaviors were collected from self-administered questionnaires. The median plasma 25(OH)D level was 17.2 ng/mL, with the range varying from 2.2 to 72.7 ng/mL (recommended range is 20-30 ng/mL). Factors associated with lower 25(OH)D level included older age, black race, lower dietary and supplemental vitamin D intake, higher Body Mass Index (BMI), ECOG performance status of 1 versus 0 and lower physical activity. Additionally, patients whose blood specimens were drawn in the winter and spring months had significantly lower 25(OH)D level, as did patients who were from the Northern and Northeastern parts of the United States. Vitamin D supplement use was uncommon in this patient population. After adjusting for pathologic and clinical prognostic factors, patients in the group with the highest level of 25(OH)D had significantly improved median OS compared to those in the group with the lowest level (32.6 vs 24.5 months; HR=0.67, P trend 0.002). Higher level of 25(OH)D was also associated with improved PFS (median 12.2 vs 10.1 months; HR 0.80, P trend = 0.02). These results were consistent across all subgroups of patients. The authors concluded that higher plasma level of 25(OH)D was associated with significantly improved survival in metastatic CRC patients treated with a combination of chemotherapy and biologic agents. With 30-35% of the malignancies attributed to dietary habits, the onus is therefore on the treating physicians to provide nutrition counseling during and after cancer treatment. Recommending vitamin D supplements for those patients with colon cancer with low vitamin D levels, may therefore not be unreasonable. Vitamin D status and survival of metastatic colorectal cancer patients: Results from CALGB/SWOG 80405 (Alliance). Ng K, Venook AP, Sato K, et al. J Clin Oncol 33, 2015 (suppl 3; abstr 507)