Matthew R. Smith, P. Kantoff, W. Oh, Grace A. Elson, J. Manola, M. McMullin, J. Jacobsen, A. Brufsky, D. Kaufman
{"title":"Phase II Trial of the Antiestrogen Toremifene for Androgen‐Independent Prostate Cancer","authors":"Matthew R. Smith, P. Kantoff, W. Oh, Grace A. Elson, J. Manola, M. McMullin, J. Jacobsen, A. Brufsky, D. Kaufman","doi":"10.1046/J.1525-1411.1999.14003.X","DOIUrl":null,"url":null,"abstract":"Objectives: Estrogen receptors are expressed in healthy and malignant prostate epithelium. Previous studies of the antiestrogen tamoxifen (20–100 mg po qd) for recurrent or metastatic prostate cancer (CaP) reported response rates of 0–23%. These studies may have underestimated the activity of antiestrogens, however, because of their reliance on insensitive clinical and radiographic response criteria. In addition, treatment-related increases in androgen levels among men who initiated treatment with noncastrate testosterone levels may have confounded the results. The aims are to evaluate the activity of the antiestrogen toremifene, a triphenylethylene derivative antiestrogen related chemically and pharmacologically to tamoxifen, in men with androgen-independent CaP using prostate specific antigen (PSA) response criteria and to determine the effect of toremifene treatment on serum testosterone levels in castrated men. \n \n \n \nMaterials and Methods: Fifteen men (median age 71 years; median PSA 58.5 ng/ml) with castrate testosterone levels, no disease-related symptoms, and rising PSA after androgen deprivation and antiandrogen withdrawal were treated with toremifene, 60 mg po qd, until it was determined that the patient was not responding to treatment. Nonresponse to treatment was defined as symptomatic disease progression or a PSA level 150% study nadir on two determinations at least 4 weeks apart. Response was defined as >50% PSA decrease on two determinations at least 4 weeks apart. \n \n \n \nResults: Twelve men were evaluable for response. Median time to determination of nonresponse to treatment was 16 weeks (range 8 to 19 weeks). There were no responses to treatment (response rate 0%; 95% confidence interval 0–22%). Treatment did not significantly change serum testosterone levels. \n \n \n \nConclusions: These results indicate that toremifene is inactive for the treatment of androgen-independent CaP and suggest that antiestrogens should not be used routinely as secondary hormonal therapy. The treatment of castrated men with toremifene does not significantly change serum testosterone levels.","PeriodicalId":22947,"journal":{"name":"The open prostate cancer journal","volume":"121 1","pages":"185-189"},"PeriodicalIF":0.0000,"publicationDate":"1999-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"The open prostate cancer journal","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1046/J.1525-1411.1999.14003.X","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 1
Abstract
Objectives: Estrogen receptors are expressed in healthy and malignant prostate epithelium. Previous studies of the antiestrogen tamoxifen (20–100 mg po qd) for recurrent or metastatic prostate cancer (CaP) reported response rates of 0–23%. These studies may have underestimated the activity of antiestrogens, however, because of their reliance on insensitive clinical and radiographic response criteria. In addition, treatment-related increases in androgen levels among men who initiated treatment with noncastrate testosterone levels may have confounded the results. The aims are to evaluate the activity of the antiestrogen toremifene, a triphenylethylene derivative antiestrogen related chemically and pharmacologically to tamoxifen, in men with androgen-independent CaP using prostate specific antigen (PSA) response criteria and to determine the effect of toremifene treatment on serum testosterone levels in castrated men.
Materials and Methods: Fifteen men (median age 71 years; median PSA 58.5 ng/ml) with castrate testosterone levels, no disease-related symptoms, and rising PSA after androgen deprivation and antiandrogen withdrawal were treated with toremifene, 60 mg po qd, until it was determined that the patient was not responding to treatment. Nonresponse to treatment was defined as symptomatic disease progression or a PSA level 150% study nadir on two determinations at least 4 weeks apart. Response was defined as >50% PSA decrease on two determinations at least 4 weeks apart.
Results: Twelve men were evaluable for response. Median time to determination of nonresponse to treatment was 16 weeks (range 8 to 19 weeks). There were no responses to treatment (response rate 0%; 95% confidence interval 0–22%). Treatment did not significantly change serum testosterone levels.
Conclusions: These results indicate that toremifene is inactive for the treatment of androgen-independent CaP and suggest that antiestrogens should not be used routinely as secondary hormonal therapy. The treatment of castrated men with toremifene does not significantly change serum testosterone levels.