Phase II trial of tamoxifen, etoposide, mitoxantrone, and cisplatin in patients with metastatic breast carcinoma

BACKGROUND. Based on previous data demonstrating a potentially synergistic interaction between tamoxifen and cisplatin in metastatic melanoma therapy, a Phase II study was performed to assess the activity of tamoxifen, etoposide, mitoxantrone, and cisplatin (TEMP) in patients with metastatic breast carcinoma. METHODS. Forty-six patients with metastatic breast carcinoma were treated with tamoxifen, 10 mg orally, twice a day for 28 days; etoposide, 100 mg/m², on Days 1-3; mitoxantrone, 10 mg/m² on Day 1; and cisplatin, 30 mg/m², on Days 1 and 2. Forty-four patients (7 with bone-only disease) were evaluable for response and toxicity after at least 1 cycle of therapy. All patients had previously received doxorubicin- containing in either the adjuvant or metastatic setting. RESULTS. The overall objective response rate for the 37 patients with visceral and/or soft tissue disease was 41% (95% confidence interval, 25-58%). The objective response rate among women previously treated with doxorubicin in the adjuvant setting was 58% (14 of 24). Only 1 of 13 patients with metastatic carcinoma who had failed doxorubicin responded. Five of seven patients with bone-only disease had subjective improvement of bone pain without worsening of bone scans. Approximately 59% of patients had Grade 3 or 4 neutropenia at some time in their therapy and 1 patient died of neutropenic sepsis. Logistic regression analysis (n = 37) revealed that response was not related to estrogen receptor (ER) status or to the presence of visceral metastases CONCLUSIONS. TEMP appears to be an active regimen for patients with either ER positive (tamoxifen-resistant) or ER negative metastatic breast carcinoma that progresses after adjuvant doxorubicin therapy. Moreover, among patients who developed metastatic disease either during or <12 months after adjuvant doxorubicin therapy, TEMP had a higher response rate than would have been predicted from previous studies. Although the mechanism remains to be elucidated, these results suggest a potentially synergistic role for tamoxifen in etoposide/cisplatin-based chemotherapy of breast carcinoma.