Effects of steroid ointment application on chemotherapy-induced phlebitis: A randomized, double-blind, placebo-controlled clinical trial

Abstract

Background: Phlebitis is a very common side effect of continuous intravenous infusion of 5-fluorouracil via the peripheral veins. We evaluated the preventive effects of topical steroid application on fluorouracil-induced phlebitis in a randomized, double-blind, placebo-controlled trial. Methods: Patients were randomly selected to receive either petroleum jelly plus steroid ointment (steroid group) or petroleum jelly ointment only (placebo group) at the Kyoto University Hospital. The main eligibility criteria were as follows: planned to undergo at least 1 course of cisplatin and 5-fluorouracil (CF) therapy; planned to receive anticancer drugs via the peripheral veins; not requiring steroid ointment on the arm (e.g., dermatitis treatment); and provided signed informed consent. Patients applied the ointments twice daily (morning and evening) during CF therapy. We assessed pigmentation and induration 24 hours and 1 month after CF therapy. To assess the effectiveness of petroleum jelly itself, the effects of the placebo and historical control (n =14, no ointment) were also compared. The Fisher's exact test (incidence) and log-rank test (time to events) were used for statistical analysis. Results: We randomly assigned 46 patients to the steroid and placebo groups (n = 23 each). All patients applied their respective ointments. Forty-five subjects were included in the analysis, excluding 1 patient in the placebo group who applied the steroid ointment due to extravasation. The incidence of clinically significant phlebitis was lower in the steroid than in the placebo group (pigmentation: 24 hours, 0% vs. 22%, P = 0.05; 1 month, 18% vs. 48%, P=0.06; induration: 24hours, 0% vs. 0%, P=1.00; 1month, 5% vs. 39%, P = 0.01). Pigmentation occurred earlier in the placebo group (placebo, median 6 days; steroid, median 13.5 days; P = 0.363). The incidence rates of phlebitis were significantly lower in the placebo group than in the historical control (52% vs. 86%; P=0.04). Conclusions: Patients receiving petroleum jelly plus steroid topical ointment clinically showed alleviation of CF-therapy-induced phlebitis, indicating the effectiveness of these agents in preventing phlebitis.