PHASE-II TRIAL OF TAMOXIFEN, ETOPOSIDE, MITOXANTRONE, AND CISPLATIN IN PATIENTS WITH METASTATIC BREAST-CARCINOMA

BACKGROUND. Based on previous data demonstrating a potentially synergi stic interaction between tamoxifen and cisplatin in metastatic melanom a therapy, a Phase II study was performed to assess the activity of ta moxifen, etoposide, mitoxantrone, and cisplatin (TEMP) in patients wit h metastatic breast carcinoma. METHODS. Forty-six patients with metast atic breast carcinoma were treated with tamoxifen, 10 mg orally, twice a day for 28 days; etoposide, 100 mg/m(2), on Days 1-3; mitoxantrone, 10 mg/m(2), on Day 1; and cisplatin, 30 mg/m(2), on Days 1 and 2. For ty-four patients (7 with bone-only disease) were evaluable for respons e and toxicity after at least 1 cycle of therapy. All patients had pre viously received doxorubicin-containing regimens in either the adjuvan t 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 wo men 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 bane-only di sease had subjective improvement of bone pain without worsening of bon e 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 r elated to estrogen receptor (ER) status or to the presence of visceral metastases. CONCLUSIONS. TEMP appears to be an active regimen for pat ients with either ER positive (tamoxifen-resistant) or ER negative met astatic breast carcinoma that progresses after adjuvant doxorubicin th erapy. Moreover, among patients who developed metastatic disease eithe r during or < 12 months after adjuvant doxorubicin therapy, TEMP had a higher response rate than would have been predicted from previous stu dies. Although the mechanism remains to be elucidated, these results s uggest a potentially synergistic role for tamoxifen in etoposide/cispl atin-based chemotherapy of breast carcinoma. (C) 1996 American Cancer Society.