Phase I/II trial of all-trans retinoic acid and tamoxifen in patients with advanced breast cancer.

摘要: Because tamoxifen and all-trans-retinoic acid (ATRA) have additive antitumor effects in preclinical systems, we performed a Phase I/II clinical trial of this combination patients with advanced breast cancer. Patients potentially hormone-responsive cancer were enrolled. All received 20 mg by mouth daily. Consecutive cohorts 3-6 treated on odd-numbered weeks ATRA at doses 70, 110, 150, 190, or 230 mg/m2/day. Twenty-six entered trial; 25 evaluable. A dose mg/m2 produced unacceptable headache dermatological toxicity, but < = 190 tolerable. Two 7 measurable disease responded. Seven 18 evaluable, nonmeasurable achieved stability for more than 6 months. Plasma AUCs day 1 successive treatment stable over time. nonsignificant decrease serum insulin-like growth factor I levels was noted during treatment, trend similar to that observed three "control" alone. When given daily tamoxifen, the maximum tolerated could be alternate This schedule resulted repeated periods exposure therapeutic concentrations ATRA. Declines those Objective responses observed, some who had previously progressed while receiving suggesting further studies would interest.