A Phase I/II Trial of Docetaxel Followed by Infusional Flavopiridol Over 72 Hours in Patients With Previously Treated Locally Advanced or Metastatic Breast Cancer
A Phase I/II Trial of Docetaxel Followed by Infusional Flavopiridol Over 72 Hours in Patients With Previously Treated Locally Advanced or Metastatic Breast Cancer
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.
PURPOSE: Phase I/II trial to study the effectiveness of combination chemotherapy in treating patients who have locally advanced or metastatic breast cancer.
OBJECTIVES:
OUTLINE: This is a dose-escalation study.
Patients receive docetaxel IV over 1 hour on day 1 followed by flavopiridol IV over 1 hour or IV continuously on days 2-4. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Sequential dose escalation of docetaxel is preceded or followed by sequential dose escalation of flavopiridol. Cohorts of 3-6 patients receive escalating doses of docetaxel preceded or followed by escalating doses of flavopiridol until the maximum tolerated dose (MTD) of the combination is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 22 additional patients are accrued to receive flavopiridol and docetaxel at the recommended phase II dose.
Quality of life is assessed at baseline, every 3 courses during study, and then at completion of study.
PROJECTED ACCRUAL: A total of 49 patients (27 for phase I and 22 for phase II) will be accrued for this study within 2 years.
DISEASE CHARACTERISTICS:
Histologically confirmed stage III or IV adenocarcinoma of the breast
Phase I:
Phase II:
No bone metastasis as only site of disease
No carcinomatous meningitis or brain metastases
Hormone receptor status:
PATIENT CHARACTERISTICS:
Age:
Sex:
Menopausal status:
Performance status:
Life expectancy:
Hematopoietic:
Hepatic:
Renal:
Cardiovascular:
Other:
PRIOR CONCURRENT THERAPY:
Biologic therapy:
Chemotherapy:
No prior flavopiridol
Prior adjuvant chemotherapy for advanced disease allowed if within 6 months of diagnosis of metastatic disease
At least 4 weeks since prior chemotherapy (6 weeks for nitrosourea or 8 weeks for UCN-01) and recovered
Phase I:
Phase II:
Endocrine therapy:
Radiotherapy:
Surgery:
Other: