Tamoxifen and meglumine antimoniate combined therapy in cutaneous leishmaniasis patients: a randomised trial.

OBJECTIVES: There is a clear need for new strategies of leishmaniasis treatment. This work was conducted to evaluate the efficacy of the co-administration of tamoxifen and meglumine antimoniate (SbV ) in a phase II pilot clinical trial in localised cutaneous leishmaniasis patients. METHODS: A randomised controlled pilot clinical trial was conducted to evaluate the efficacy and safety of oral (40 mg/day for 20 days) or topical tamoxifen (0.1% tamoxifen citrate for 20 days) combined with meglumine antimoniate (20 mg SbV /kg/day for 20 days) vs. a standard SbV protocol (20 mg/kg/day for 20 days) for the treatment of cutaneous leishmaniasis. Primary outcome was complete epithelisation of the lesion 6 months after the end of treatment. Secondary outcomes were lesion healing 2 months after the end of treatment and frequency and severity of adverse events. RESULTS: A total of 38 subjects were included in the trial, 15 were treated with standard SbV and 23 with the combination of tamoxifen and SbV . Of the patients treated with the co-administration scheme, 12 received tamoxifen orally and 11 were treated with topical tamoxifen. Tamoxifen administered by the oral or topical routes was well tolerated. Cure rates 6 months after the end of treatment per intention to treat were 40% in the group treated with the standard SbV scheme, and 36.4% and 58%, respectively, for groups treated with SbV plus topical or oral tamoxifen. CONCLUSIONS: In the doses and schemes used in this study, co-administration of oral tamoxifen and SbV resulted in higher cure rates in comparison with the standard scheme of treatment, although not to statistically significant levels.

Fluconazole in the Treatment of Cutaneous Leishmaniasis Caused by Leishmania braziliensis: A Randomized Controlled Trial.

BACKGROUND: The treatment of cutaneous leishmaniasis (CL) caused by Leishmania braziliensis in Brazil with pentavalent antimony (Sbv) is associated with a high rate of failure, up to 45% of cases. In addition, Sbv can only administered parenterally and has important toxic effect. An effective, safe, and oral treatment for CL is required. METHODS: A randomized controlled clinical trial was conducted to compare the efficacy and safety of high-dosage oral fluconazole (6.5-8.0 mg/kg/d for 28 days) versus a standard Sbv protocol (20 mg/kg/d for 20 days) for the treatment of CL in Bahia, Brazil. RESULTS: A total of 53 subjects were included in the trial; 26 were treated with Sbv, and 27 with fluconazole. Intention-to-treat analysis showed initial cure rates (2 months after treatment) of 22.2% (6 of 27) in the fluconazole and 53.8% (14 of 26) in the Sbv group (P = .04). Six months after treatment, the final cure rate remained the same in both groups, without any relapses. The frequencies of adverse effects in the Sbv and fluconazole groups were similar, 34.6% versus 37% respectively. One patient treated with fluconazole discontinued treatment owing to malaise, headache, and moderate dizziness (Common Terminology Criteria for Adverse Events grade 2). CONCLUSIONS: Oral fluconazole at a dosage of 6.5-8 mg/kg/d for 28 days should not be considered an effective treatment for CL caused by L. braziliensisClinical Trials Registration. NCT01953744.