1.
Relative efficacy of 5-fluorouracil compared with other treatments among patients with actinic keratosis: A network meta-analysis.
Wu, Y, Tang, N, Cai, L, Li, Q
Dermatologic therapy. 2019;(3):e12822
Abstract
OBJECTIVE The purpose of this study was to compare the efficacy of 5-fluorouracil (5-FU) with that of other treatments of actinic keratosis (AK). METHODS A systematic literature review of five databases (including Medline and EMBASE) was first performed to identify randomized controlled trials (RCTs). A network meta-analysis (NMA) based on a random-effects Bayesian model was then performed on the outcomes for patients with total clearance and lesions reduced from baseline. Five treatments (viz., 0.5% 5-FU with 10% salicylic acid [5-FU/SA], 5% 5-FU cream, 3% diclofenac sodium, cryosurgery, and vehicle) were evaluated. RESULTS A total of 11 studies involving 2,256 patients with AK were included in this NMA. The overall risk of bias among the included studies was low. All treatments were significantly better than the vehicle both for patients with total clearance and for lesions reduced from baseline. Among patients with total clearance, 5% 5-FU cream (56.8%) and 5-FU/SA (35.7%) were likely to be more effective than the other treatments, whereas 5% 5-FU cream (98.6%) was likely the most effective in the group of lesions reduced from baseline. CONCLUSION 5-FU, diclofenac sodium, and cryosurgery are all useful for AK treatment, with 5-FU being the most effective.
2.
Irinotecan- and 5-fluorouracil-induced intestinal mucositis: insights into pathogenesis and therapeutic perspectives.
Ribeiro, RA, Wanderley, CW, Wong, DV, Mota, JM, Leite, CA, Souza, MH, Cunha, FQ, Lima-Júnior, RC
Cancer chemotherapy and pharmacology. 2016;(5):881-893
Abstract
PURPOSE Intestinal mucositis and diarrhea are common manifestations of anticancer regimens that include irinotecan, 5-fluorouracil (5-FU), and other cytotoxic drugs. These side effects negatively impact therapeutic outcomes and delay subsequent cycles of chemotherapy, resulting in dose reductions and treatment discontinuation. Here, we aimed to review the experimental evidence regarding possible new targets for the management of irinotecan- and 5-FU-related intestinal mucositis. METHODS A literature search was performed using the PubMed and MEDLINE databases. No publication time limit was set for article inclusion. RESULTS Here, we found that clinical management of intestinal mucositis and diarrhea is somewhat ineffective at reducing symptoms, possibly due to a lack of specific targets for modulation. We observed that IL-1β contributes to the apoptosis of enterocytes in mucositis induced by 5-FU. However, 5-FU-related mucositis is far less thoroughly investigated with regard to specific molecular targets when compared to irinotecan-related disease. Several studies have proposed that a correlation exists between the intestinal microbiota, the enterohepatic recirculation of active metabolites of irinotecan, and the establishment of mucositis. However, as reviewed here, this association seems to be controversial. In addition, the pathogenesis of irinotecan-induced mucositis appears to be orchestrated by interleukin-1/Toll-like receptor family members, leading to epithelial cell apoptosis. CONCLUSIONS IL-1β, IL-18, and IL-33 and the receptors IL-1R, IL-18R, ST2, and TLR-2 are potential therapeutic targets that can be modulated to minimize anticancer agent-associated toxicity, optimize cancer treatment dosing, and improve clinical outcomes. In this context, the pathogenesis of mucositis caused by other anticancer agents should be further investigated.