An open-label randomized phase II trial of oral vitamin D3 supplementation in combination with standard chemotherapy or best supportive care compared with standard chemotherapy and best supportive care in patients with advanced solid tumors.

Abstract

e19566 Background: The majority of patients with newly diagnosed stage IV cancer are vitamin D deficient at the time of diagnosis. We conducted a phase II trial to evaluate the efficacy and safety of oral supplementation with 25-hydroxyvitamin D3 [25(OH)D] in chemotherapy-naive patients. Methods: Eligibility critera included ECOG PS 0-3, low serum 25-hydroxyvitamin D3 [25(OH)D] at the time of diagnosis (using cutoff value of 32 nmol/L) and normal serum calcium level. Patients were randomized to receive oral supplementation with 2,000 IU of Vitamin D3 daily for 6 months with standard therapy or to continue standard treatment without vit D supplementation. Results: Sixty-seven patients were accrued, 42 were males and 25 females. The most common primary cancer sites were lung (36, 54%), colorectum (14, 21%), pancreas (7, 10%), breast (7, 10%) and kidney (3, 5%). The median 25 (OH) D level for all patients was 20,69 nmol/L. Response is evaluated by RECIST criteria at 8 weeks and toxicity was graded by the NCI CTCAE. No patient had a complete response, but ORR were significantly better in experimental arm (18% versus 6%, p=0.036). Vit D was well tolerated; the most common toxicities were neutropenia, diarrhoea, fatigue, nausea and constipation. Four patients had grade 1-2 of hypercalcemia (Table). Conclusions: The safety profile of vitamin D in combination with chemotherapy or BSC was acceptable and ORR was significantly greater for patients receiving oral vit D supplementation. However, there was no significant difference between the two arms in terms of 6 months survival rates. These data suggest that adding vit D to an already-effective treatment may result in clinical benefit beyond that associated with combination chemotherapy or BSC alone. Experimental arm (n=33) Control arm (n=34) P Vitamin D median nmol/L 19.64 21.72 0.40 Age median years 66 65 0.62 Male gender 22 20 0.15 Date of diagnosis 0.49 Winter-Spring 15 16 Summer-Autumn 17 17 Treatment 0.86 Chemotherapy 22 22 BSC 11 12 ORR 6 (18%) 2 (6%) 0.036 AE gr 3 or 4 8 8 0.95 Hypercalcemia 1 3 0.32