Evaluation of tamoxifen dose in advanced breast cancer: A progress report

The results of an ongoing trial randomizing patients with progressive, metastatic breast carcinoma between tamoxifen (Tam, NSC 180973) and Tam plus fluoxymesterone (Flu) (7 mg/m ² bid) are reported. Each patient received a single dose level of Tam in the range of 2-100 mg/m ² bid. The combination had a higher response rate overall (45% vs 28%) and when only the patient's soft tissue sites were analyzed (54% vs 9%, P = 0.04). The time to treatment failure was longer for the combination among those patients with a response or disease stabilization (P = 0.08). Response rates with Tam doses < 12 mg/m ² bid were also higher than with doses ≥ 12 mg/m ² for all patients in the study (62% vs 30%, P = 0.025) and for those where only soft tissue sites were evaluable (43% vs 29%, P = 0.07). Side effects were mild and consisted primarily of transient hematologic suppression, nausea, masculinization, hepatic enzyme elevations, and edema. The latter three were observed only with the Flu regimen. Leukopenia and thrombocytopenia were more frequent at Tam doses < 12 mg/m ² bid whereas nausea was more common at higher doses. Tam doses as high as 100 mg/m ² bid were well tolerated. Tam may be more effective at low doses, has only mild side effects, and is well tolerated at doses up to 100 mg/m ² bid. Combining Tam with Flu appears to enhance the therapeutic effectiveness.