Phase I study of toremifene in patients with advanced cancer.
A phase I multicenter evaluation of a novel antiestrogen, toremifene, was undertaken in postmenopausal women with various advanced difficult-to-treat malignancies. One hundred and seven women were treated at one of six dosage levels (10, 20, 40, 60, 200, or 400 mg/d orally) for at least 8 weeks. Weekly evaluations for toxicity were conducted. The most common side effects were nausea (31%), vomiting (12%), and hot flashes (29%). Five patients were removed from the study for possible adverse reactions: three patients experienced hypercalcemia; one experienced tremulousness, fatigue, and inability to think clearly; and one had vaginal bleeding. Twelve patients died while on study, 11 with disease progression and one with a pulmonary embolus. Sex hormone-binding globulin (SHBG) levels increased and there was a modest decline in serum antithrombin III levels. Four of 48 assessable patients had partial responses: three with breast cancer and one with endometrial cancer. Toremifene was generally well tolerated at the doses tested.
Hamm
J T
JT
Department of Medicine, University of Louisville, KY 40292.
Tormey
D C
DC
Kohler
P C
PC
Haller
D
D
Green
M
M
Shemano
I
I
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000990:Antithrombin III / Q000187:drug effects; D004341:Drug Evaluation; D004965:Estrogen Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006062:Gonadotropins / Q000097:blood; D006801:Humans; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D012738:Sex Hormone-Binding Globulin / Q000187:drug effects; D013629:Tamoxifen / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017312:Toremifene
D000970:Antineoplastic Agents; D004965:Estrogen Antagonists; D006062:Gonadotropins; D012738:Sex Hormone-Binding Globulin; D013629:Tamoxifen; D017312:Toremifene; D000990:Antithrombin III