title: A phase I/II investigation of trioxifene mesylate in advanced breast cancer. Clinical and endocrinologic effects.
abstract: 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.
authors.forename: R S
authors.initials: RS
authors.lastname: Witte
authors.forename: B
authors.initials: B
authors.lastname: Pruitt
authors.forename: D C
authors.initials: DC
authors.lastname: Tormey
authors.forename: S
authors.initials: S
authors.lastname: Moss
authors.forename: D P
authors.initials: DP
authors.lastname: Rose
authors.forename: G
authors.initials: G
authors.lastname: Falkson
authors.forename: P P
authors.initials: PP
authors.lastname: Carbone
authors.forename: G
authors.initials: G
authors.lastname: Ramirez
authors.forename: H
authors.initials: H
authors.lastname: Falkson
authors.forename: F J
authors.initials: FJ
authors.lastname: Pretorius
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D004702:Endocrine Glands / Q000187:drug effects*; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D005260:Female; D013006:Growth Hormone / Q000378:metabolism; D006801:Humans; D011388:Prolactin / Q000378:metabolism; D011759:Pyrrolidines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004965:Estrogen Antagonists; D011759:Pyrrolidines; D012738:Sex Hormone-Binding Globulin; D013973:Thyrotropin-Releasing Hormone; D011388:Prolactin; D013006:Growth Hormone; C014934:trioxifene