Randomized Clinical Chemoprevention Trial of Lyophilized Strawberries in Patients with Dysplastic Precancerous Lesions of the Esophagus
Mené sur 75 patients présentant des lésions dysplasiques de l'oesophage, cet essai randomisé chinois évalue les effets chimiopréventifs de fraises lyophilisées et congelées sur la carcinogenèse
Dysplasia is a histologic precursor of esophageal squamous cell carcinoma (SCC). We previously showed that dietary freeze-dried, or lyophilized, strawberry powder inhibits N-nitrosomethylbenzylamine-induced SCCs in the rat esophagus. Based on this observation, we conducted a randomized (noncomparative) phase II trial in China to investigate the effects of two doses of freeze-dried strawberries in patients with esophageal dysplastic lesions in a high-risk area for esophageal cancer. We randomly assigned 75 patients identified by endoscopy to have dysplastic esophageal premalignant lesions to receive freeze-dried strawberry powder at either 30 grams/day (37 patients) or 60 grams/day (38 patients) for six months; the powder was mixed with water and drunk. After six months, we assessed the changes in histological grade of these lesions (primary endpoint) in a blinded fashion. The dose of 30 grams/day, did not significantly affect histology or any other measured parameter. The dose of 60 grams/day, however, reduced the histological grade of dysplastic premalignant lesions in 29 (80.6%) of the 36 patients at this dose who were evaluated for histology (P < 0.0001). The strawberry powder was well tolerated, with no toxic effects or serious adverse events. Strawberries (60 grams/day) also reduced protein expression levels of inducible nitric oxide synthase (iNOS) by 79.5% (P < 0.001), cyclooxygenase-2 (COX-2) by 62.9% (P < 0.001), phosphonuclear factor kappa B (NFκB)-p65 (pNFκB-p65) by 62.6% (P < 0.001), and phospho-S6 (pS6) by 73.2% (P < 0.001). Freeze-dried strawberries (60 grams/day) also significantly inhibited the Ki-67 labeling index by 37.9% (P = 0.023). Our present...