Formelli F, Carsana R, Costa A, Buranelli F, Campa T, Dossena G, Magni A, Pizzichetta M
Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Cancer Res. 1989 Nov 1;49(21):6149-52.
Fenretinide (HPR) is a synthetic retinoid which has been shown to cause a reduction in the incidence of carcinogen-induced epithelial tumors in experimental animals, and it has been chosen to be tested as a chemopreventive agent in humans. A study on plasma concentrations of HPR, of its metabolite N-(4-methoxyphenyl)retinamide (MPR), and on its effects on endogenous retinol was performed in groups of 14 to 18 breast cancer patients who received p.o. daily doses of placebo or 100, 200, and 300 mg of HPR for 6 mo and subsequently 200 mg for an additional 6 mo. After the first 5 mo of treatment, there was a linear relationship between doses of HPR administered and HPR, MPR, and retinol levels. HPR and MPR levels increased with the increase in dose, whereas retinol levels decreased, and the reduction was statistically significant compared with the placebo group after all the doses tested. Plasma retinol binding proteins (RBP) decreased proportionally to retinol (r = 0.96). The effect of HPR on retinol and RBP occurred early, since retinol and RBP levels had already been decreased, compared with the initial levels, by 38% and 26%, respectively, 24 h after a 200-mg HPR dose. After 12 mo of treatment, in patients treated with 200 mg daily, the dose chosen for a chemopreventive trial, HPR and retinol levels were similar to those found at 5 mo, suggesting no drug accumulation and no further retinol reduction, whereas MPR levels were higher. Following interruption of treatment, as HPR decreased, retinol increased with a linear relationship between log levels (r = 0.78); after about 50 days, HPR was present in trace amounts, and retinol levels were in the range of those of the placebo group. These data show that HPR treatment lowers retinol and RBP plasma concentrations. This effect is related to HPR levels and is reversible on cessation of HPR administration.
芬维A胺（HPR）是一种合成类视黄醇，已证明它能降低实验动物中致癌物诱发的上皮肿瘤的发生率，并且已被选作人类化学预防剂进行试验。对14至18名乳腺癌患者进行了一项研究，这些患者口服安慰剂或每日剂量为100、200和300毫克的HPR，为期6个月，随后再以200毫克的剂量服用6个月。研究测定了他们血浆中HPR、其代谢产物N-（4-甲氧基苯基）视黄酰胺（MPR）的浓度，以及HPR对内源性视黄醇的影响。在治疗的前5个月后，所给予的HPR剂量与HPR、MPR和视黄醇水平之间存在线性关系。HPR和MPR水平随剂量增加而升高，而视黄醇水平降低，与所有测试剂量的安慰剂组相比，这种降低具有统计学意义。血浆视黄醇结合蛋白（RBP）与视黄醇成比例下降（r = 0.96）。HPR对视黄醇和RBP的影响出现得较早，因为在给予200毫克HPR剂量24小时后，与初始水平相比，视黄醇和RBP水平分别已经下降了38%和26%。治疗12个月后，在接受每日200毫克治疗（这是化学预防试验所选用的剂量）的患者中，HPR和视黄醇水平与5个月时相似，表明没有药物蓄积且视黄醇没有进一步降低，而MPR水平较高。治疗中断后，随着HPR下降，视黄醇升高，对数水平之间呈线性关系（r = 0.78）；大约50天后，HPR含量微量，视黄醇水平处于安慰剂组的范围内。这些数据表明，HPR治疗可降低视黄醇和RBP的血浆浓度。这种作用与HPR水平有关，并且在停止给予HPR后是可逆的。
