Weekly docetaxel in pretreated metastatic breast cancer patients: a phase I-II study.
OBJECTIVE
We conducted a phase I-II study to determine the maximum tolerated dose (MTD), toxicity and activity of weekly docetaxel administration in pretreated metastatic breast cancer patients.


METHODS
In phase I, cohorts of 3 women with pretreated metastatic breast cancer were treated with a 1-hour infusion of docetaxelat 30, 35, 40 mg/m2/week after premedication with two doses of dexamethazone 8 mg 12 h apart. Subsequently, a cohort of 28 women was treated at the MTD for 24 consecutive weeks in a phase II setting and was assessed for toxicity and activity.


RESULTS
Three patients were treated at each of the first two dose levels; 9 patients were treated at the 3rd level (40 mg/m2/week). Dose-limiting toxicities (DLTs) were experienced at that level by 2/6 patients of the first two accrued groups and in 2/3 patients of the 3rd (confirmation) group, thus establishing the subsequent phase II dose at 35 mg/m2/week. Two out of 28 evaluable patients (7.1%, 95% CI 0-16.7) showed complete responses, whereas 8 (28.6%, 95% CI 11.8-45.3) showed partial responses, and an objective response rate of 35.7% (95% confidence interval, CI 18-53.5%). In addition, 8 patients (28.6%) had stable disease. The median time to progression and overall survival were 5 (range 1-15) and 15 months (95% CI 7-23), respectively. One patient experienced 1 episode of grade 3 neutropenia. Severe asthenia was the main reason for interruption of chemotherapy (10 patients, 35.5%).


CONCLUSIONS
In pretreated metastatic breast cancer patients, the sustained weekly administration of docetaxel, even though it demonstrated an activity similar to a 3-weekly schedule could not be maintained for the planned 24 weeks due to the progressive emergence of nonhematological side effects that approached DLTs.
Nisticò
Cecilia
C
Department of Medical Oncology, Regina Elena National Cancer Institute, Roma, Italy. cnistico@ifo.it
Cognetti
Francesco
F
Frontini
Luciano
L
Barni
Sandro
S
Ferretti
Gianluigi
G
Bria
Emilio
E
Milella
Michele
M
Garufi
Carlo
C
Cuppone
Federica
F
Vanni
Barbara
B
Carlini
Paolo
P
Terzoli
Edmondo
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000556:secondary; D000077143:Docetaxel; D005260:Female; D006801:Humans; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D015996:Survival Rate; D043823:Taxoids / Q000627:therapeutic use*; D016896:Treatment Outcome
D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel