A phase I/II investigation of trioxifene mesylate in advanced breast cancer. Clinical and endocrinologic effects

✍ Scribed by Robert S. Witte; Brian Pruitt; Douglass C. Tormey; Scot Moss; David P. Rose; Paul P. Carbone; Guillermo Ramirez; Geoffrey Falkson; Hendre Falkson; Florence J. Pretorius

• Publisher: John Wiley and Sons
• Year: 1986
• Tongue: English
• Weight: 586 KB
• Volume: 57
• Category: Article
• ISSN: 0008-543X
• DOI: 10.1002/1097-0142(19860101)57:1<34::aid-cncr2820570109>3.0.co;2-w

✦ Synopsis

Tamoxifen and trioxifene are antiestrogens that appear to have different endocrine effects when tested in rats. Whereas tamoxifen has considerable clinical activity, trioxifene is a new antiestrogen with undefined clinical activity. Thirty-six patients were treated with graded doses of trioxifene. The low-dose group (0.5 to 12 mg/m2 twice daily) had a 21% response rate in 24 subjects, and the high-dose group (40 to 100 mg/ m2 twice daily) had a 33% response rate in 12 patients (P = 0.13). The time to treatment failure was 67 days and 178 days for the low-and high-dose groups, respectively. Toxicities were non-dose dependent; those of moderate frequency included leukopenia (41%) and nausea (31%). Tamoxifen reduced both prolactin and inducible growth hormone (GH). Trioxifene, although reducing prolactin, differed from tamoxifen in that an increase in inducible GH occurred. Furthermore, a striking dose-dependent decrease in luteinizing hormone and lesser decrease in follicle-stimulating hormone occurred only in the trioxifene-treated patients. This implies an intrinsic estrogenic action of trioxifene in man. Trioxifene is no more efficacious than tamoxifen and has more toxicity.