Sorafenib for Advanced and Refractory Desmoid Tumors.

BACKGROUND: Desmoid tumors (also referred to as aggressive fibromatosis) are connective tissue neoplasms that can arise in any anatomical location and infiltrate the mesentery, neurovascular structures, and visceral organs. There is no standard of care. METHODS: In this double-blind, phase 3 trial, we randomly assigned 87 patients with progressive, symptomatic, or recurrent desmoid tumors to receive either sorafenib (400-mg tablet once daily) or matching placebo. Crossover to the sorafenib group was permitted for patients in the placebo group who had disease progression. The primary end point was investigator-assessed progression-free survival; rates of objective response and adverse events were also evaluated. RESULTS: With a median follow-up of 27.2 months, the 2-year progression-free survival rate was 81% (95% confidence interval [CI], 69 to 96) in the sorafenib group and 36% (95% CI, 22 to 57) in the placebo group (hazard ratio for progression or death, 0.13; 95% CI, 0.05 to 0.31; P<0.001). Before crossover, the objective response rate was 33% (95% CI, 20 to 48) in the sorafenib group and 20% (95% CI, 8 to 38) in the placebo group. The median time to an objective response among patients who had a response was 9.6 months (interquartile range, 6.6 to 16.7) in the sorafenib group and 13.3 months (interquartile range, 11.2 to 31.1) in the placebo group. The objective responses are ongoing. Among patients who received sorafenib, the most frequently reported adverse events were grade 1 or 2 events of rash (73%), fatigue (67%), hypertension (55%), and diarrhea (51%). CONCLUSIONS: Among patients with progressive, refractory, or symptomatic desmoid tumors, sorafenib significantly prolonged progression-free survival and induced durable responses. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT02066181 .).

Novel antioxidant technology for prostate cancer chemoprevention and treatment.

The mechanisms underlying prostate carcinogenesis are not firmly elucidated. An exciting area of research in this regard asks whether prostate cancer results from the consequences of lifelong exposure of prostate tissue to oxidative stress. This article reviews the laboratory-based literature on oxidative stress and its possible role in prostate carcinogenesis. The progression of clinical studies focusing on the relationship between antioxidant supplementation and risk of developing prostate cancer are discussed, along with the patent literature since 2003 involving novel antioxidant technology applicable to prostate cancer prevention and treatment. In particular, recently published in vitro experiments with a novel alpha-tocopherol analogue, 2,2,5,7,8-pentamethyl-6-chromonal, which characterised its unique spectrum of antioxidant and antiandrogen properties in prostate cancer cell lines, is discussed. In addition, recent patent applications and supporting findings from the literature surrounding: i) cisplatin tocopherol compounds; ii) coix seed soft capsules with vitamin E; iii) vitamin E succinate (alpha-tocopheryl succinate); iv) lycopene preparations with other carotenoids; v) compounds of the ginger family; vi) novel aryl-carbaldehyde oxime derivatives; vii) novel phenyl quinoline derivatives; and viii) resveratrol, its derivatives and preparations thereof are discussed as they relate to prostate cancer chemoprevention and treatment.