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Twenty-six patients with relapsed or drug-resistant cancer were treated with a combination of oral etoposide (300 mg day-' for 3 days) and high-dose oral tamoxifen as a potential modulator of drug resistance (480 or 720mgday-' for 6 days beginning 3 days before etoposide). One patient with relapsed high-grade lymphoma and one with adenocarcinoma of unknown primary site has a partial response. Toxicity consisting of nausea, vomiting and subjective dizziness, unsteadiness of gait and malaise occurred during tamoxifen treatment. Serum levels of tamoxifen averaged 3-3.5 gM on day 4 of all courses of treatment at both 480 and 720 mg day-'. N-desmethyltamoxifen levels were lower than tamoxifen during the first course (2 JM) but increased to equal tamoxifen levels during the second course. Didesmethyltamoxifen levels remained below