The primary aim of this study was to evaluate the effect of folic acid on mucositis. A secondary aim was to characterize patient outcome with the current standard of care in patients with mRCC. The study cohort comprised data of 77 mRCC patients, who experienced CTCAE Grade ≥2 mucositis (nasal, oral, pharyngeal, anal, or genital) from systemic therapy, and were treated with folic acid in order to reduce the mucosal toxicity.
Patients reported an effect of folic acid within days to a few weeks. Patients reached full effect of the folic acid supplementation in 31 days (median). Daily folic acid significantly reduced mucositis, mean CTCAE grade 0.88 (95% confidence interval [CI], 0.74-1.03) versus 2.38 (95% CI, 2.26-2.54; P < .0001).
Patient outcomes were not deteriorated with the use of folic acid. Median PFS for all patients was 14 months (95% CI, 1-76 months). Median OS for all patients was 31 months (95% CI, 1-114 months), which is equal to or even better than expected for the studied patient cohort.
The present study represents, to our knowledge, the first documentation of specific therapy to reduce mucositis in mRCC patients receiving continuous therapy. To date, only supportive care to alleviate mucosal irritation has been reported, such as saltwater or sodium bicarbonate oral rinses, sucking ice, use of a soft toothbrush, steroids, and smoking cessation. Moreover, avoidance of hot, sour, salty, acidic, hard, and crunchy food, as well as avoidance of alcohol and agents that contain hydrogen peroxide are encouraged. However, these restrictions are linked with poor daily quality of life for many patients and their families.
If mucosal adverse events can be reduced, the patient daily quality of life will improve. Moreover, if overall treatment can be given without dose reduction, discontinuation, or shift in treatment, this might potentially improve treatment outcome.
Prospective validation of folic acid is ongoing: FASTERCC (Folic Acid Supplement vs. placebo for Treating mucositis adverse Events in metastatic Renal Cell Carcinoma patients receiving targeted therapy). A randomized, placebo-controlled, double-blind trial from the Danish Renal Cancer Group (DARENCA study-4; NCT03581773).
Written by: Niels Fristrup, MD, PhD and Frede Donskov, MD, DMSc, Department of Oncology, Aarhus University Hospital, Århus, Denmark
Read the Abstract