A phase I/II investigation of trioxifene mesylate in advanced breast cancer. Clinical and endocrinologic effects.
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.
Witte
R S
RS
Pruitt
B
B
Tormey
D C
DC
Moss
S
S
Rose
D P
DP
Falkson
G
G
Carbone
P P
PP
Ramirez
G
G
Falkson
H
H
Pretorius
F J
FJ
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
D000970:Antineoplastic Agents; D004965:Estrogen Antagonists; D011759:Pyrrolidines; D012738:Sex Hormone-Binding Globulin; D013973:Thyrotropin-Releasing Hormone; D011388:Prolactin; D013006:Growth Hormone; C014934:trioxifene