High-dose (480 mg/day) tamoxifen with etoposide: a study of a potential multi-drug resistance modulator.
Tamoxifen and its principle metabolite N-desmethyltamoxifen can modulate multi-drug resistance in vitro. Tamoxifen 480 mg/day was given for 6 days with oral etoposide on days 4-6 to 17 patients with advanced solid tumours. Venous thrombosis (2 patients), reversible neurological toxicity (1 patient), and WHO grade III nausea/vomiting (3 patients) related to tamoxifen were observed but overall toxicity was manageable. One partial response occurred in 15 assessable patients. Mean plasma concentrations of tamoxifen and N-desmethyltamoxifen increased to 4.3 mumol/l and 2.7 mumol/l, respectively, by day 6. Plasma concentrations corresponding to active in vitro levels were attained by most patients.
Millward
M J
MJ
University Department of Clinical Oncology, Newcastle General Hospital, Newcastle Upon Tyne, England.
Lien
E A
EA
Robinson
A
A
Cantwell
B M
BM
D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D004334:Drug Administration Schedule; D004351:Drug Resistance; D005047:Etoposide / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D012509:Sarcoma / Q000188:drug therapy; D013629:Tamoxifen / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000627:therapeutic use*; D013997:Time Factors
D013629:Tamoxifen; D005047:Etoposide; C028787:N-desmethyltamoxifen