A phase II trial of docetaxel and estramustine in patients with refractory metastatic breast carcinoma.
BACKGROUND
The similarity between the mechanism of action between docetaxel and estramustine generated the hypothesis of synergistic antimicrotubule effects and cytotoxicity when the two agents are combined. In addition, it has been demonstrated that estramustine binds P-glycoprotein in vitro and, thus, may prevent the efflux of taxanes in tumors that over-express P-glycoprotein. To further evaluate the combinations clinical efficacy and safety, a trial was performed in heavily pretreated patients with metastatic breast carcinoma (MBC).


METHODS
Thirty-six patients with MBC were treated with estramustine 900 mg/m(2) per day divided into 3 doses given on Days 1-3 and docetaxel 70 mg/m(2) given by intravenous administration over 1 hour on Day 3 after the first dose of estramustine, every 21 days. Patients may have received any number of prior chemotherapy regimens for MBC.


RESULTS
Nine partial responses were observed in 31 assessable patients, for an objective response rate of 29% (95% confidence interval, 14-48%). The median progression free survival was 4 months (range, 1-41 months), and the median overall survival was 17 months (range, 2-45 months). Severe toxicities (Grade 3 or 4) were neutropenia, hypophosphatemia, and thrombosis. Seventy-five percent of patients experienced either an improvement or no change in quality of life.


CONCLUSIONS
The combination of docetaxel and estramustine produced responses in heavily pretreated women with MBC while maintaining quality of life.
Tiersten
Amy D
AD
Department of Medicine, Division of Medical Oncology, Herbert Irving Comprehensive Cancer Center, Columbia University/New York Presbyterian Hospital, New York, New York, USA. tiersten@cancercenter.columbia.edu
Nelsen
Caron
C
Talbot
Susan
S
Vahdat
Linda
L
Fine
Robert
R
Troxel
Andrea
A
Brafman
Lois
L
Shriberg
Laureen
L
Antman
Karen
K
Petrylak
Daniel P
DP
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077143:Docetaxel; D004961:Estramustine / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D011788:Quality of Life; D012074:Remission Induction; D016019:Survival Analysis; D043823:Taxoids
D043823:Taxoids; D000077143:Docetaxel; D004961:Estramustine; D017239:Paclitaxel