Intermittent high-dose tamoxifen as a potential modifier of multidrug resistance.
In vitro tamoxifen reverses multidrug resistance (MDR). To evaluate the clinical potential of using tamoxifen in this way, intermittent high-dose tamoxifen was combined with oral etoposide in 86 patients. At 320 mg/day tamoxifen for 6 days, mean plasma levels of tamoxifen in 11 patients increased from 453 ng/ml (range 269-664) on day 2 to 984 ng/ml (578-1336) on day 6. Of 31 patients who had plasma tamoxifen measured during the time of etoposide administration (days 4-6), 13(43%) were over 1111 ng/ml (3 mumol/l), an active in vitro level. Potentially active levels of the principal metabolite, N-desmethyl tamoxifen, were also obtained but accumulation was slower. Emesis and thromboembolism were toxicities. Tamoxifen is a modifier of MDR, a role that warrants further clinical studies.
Millward
M J
MJ
University Department of Clinical Oncology, Newcastle General Hospital, Newcastle Upon Tyne, U.K.
Cantwell
B M
BM
Lien
E A
EA
Carmichael
J
J
Harris
A L
AL
D000284:Administration, Oral; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000494:pharmacology*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004351:Drug Resistance; D004357:Drug Synergism; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000188:drug therapy*; D013629:Tamoxifen / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
D013629:Tamoxifen; D005047:Etoposide