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 regimens 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 56% (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 neuropenic 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.
Department of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire 03756, USA.
S D
SD
Conzen
P A
PA
Kaufman
C
C
Arvizu
P
P
LeMarbre
L H
LH
Maurer
L A
LA
Mott
L E
LE
Mills
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D013629:Tamoxifen / Q000008:administration & dosage
D013629:Tamoxifen; D005047:Etoposide; D008942:Mitoxantrone; D002945:Cisplatin