Vinorelbine Plus Fluorouracil in Treating Women With Metastatic Breast Cancer

OBJECTIVES:

• Determine the least toxic time of vinorelbine administration when combined with chronomodulated fluorouracil in women with previously treated metastatic breast cancer.
• Determine the toxic effects and dose intensities of each drug in these women.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior chemotherapy (second line vs third line) and participating center. Patients are randomized to 1 of 8 vinorelbine dosing times (0000, 0300, 0600, 0900, 1200, 1500, 1800, or 2100).

Patients receive vinorelbine IV over 20 minutes on days 1 and 6 and fluorouracil IV over 12 hours according to a chronomodulated delivery rate (2200 to 1000 with a maximum dose at 0400) on days 1-4. Treatment repeats every 3 weeks for at least 3 courses in the absence of unacceptable toxicity.

Patients are followed for 30 days.

PROJECTED ACCRUAL: A minimum of 80 patients (10 per dosing time) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic breast cancer
• At least 1 line of prior chemotherapy for metastatic disease (adjuvant or neoadjuvant chemotherapy is considered first line if completed less than one year prior to palliative chemotherapy)
• No cerebral metastases
• Hormonal receptor status:

• Not specified

PATIENT CHARACTERISTICS:

Age:

• Not specified

Sex:

• Female

Menopausal status:

• Not specified

Performance status:

• WHO 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm ^3

Hepatic:

• Bilirubin no greater than 2.5 times upper limit of normal (ULN)
• AST/ALT no greater than 2.5 times ULN

Renal:

• Creatinine no greater than 1.58 mg/dL

Cardiovascular:

• No clinically significant cardiac insufficiency or ischemic disease

Pulmonary:

• No bronchoconstriction other than pulmonary lymphangitis

Other:

• No serious chronic disease
• No bowel obstruction
• Not pregnant or nursing

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent immunotherapy
• No concurrent prophylactic growth factor

Chemotherapy:

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy
• No prior high-dose chemotherapy
• No other concurrent chemotherapy

Endocrine therapy:

• No concurrent hormonal therapy
• No concurrent steroid therapy except in an emergency

Radiotherapy:

• At least 4 weeks since prior radiotherapy (for primary tumor or axillary or mammary chain treatment only)
• No concurrent radiotherapy

Surgery:

• Not specified

Other:

• No other concurrent antitumor therapy