• Maximum-tolerated dose (phase I) [ Designated as safety issue: No ]
• Response rate at the end of study treatment (phase II) [ Designated as safety issue: No ]
• Toxicity at the end of study treatment (phase II) [ Designated as safety issue: Yes ]

• Maximum-tolerated dose (phase I)
• Response rate at the end of study treatment (phase II)
• Toxicity at the end of study treatment (phase II)

• Time to treatment failure at end of study treatment (phase II) [ Designated as safety issue: No ]
• Quality of life by Linear Analogue Self-Assessment indicators with 6 assessments until the end of the course 4 (phase II) [ Designated as safety issue: No ]

• Time to treatment failure at end of study treatment (phase II)
• Quality of life by Linear Analogue Self-Assessment indicators with 6 assessments until the end of the course 4 (phase II)

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: This phase I/II trial is studying the side effects and best dose of capecitabine and vinorelbine and to see how well they work in treating older women with metastatic breast cancer with or without bone involvement.

OBJECTIVES:

• Determine the maximum tolerated dose of capecitabine and vinorelbine in elderly women (65 and older) with metastatic breast cancer.
• Evaluate the efficacy and tolerability of this regimen in these patients.
• Assess the time to treatment failure for this regimen as a first line chemotherapy in these patients.

OUTLINE: This is a dose-escalation study of capecitabine and vinorelbine. Patients are stratified according to bone involvement (yes [closed to accrual as of 12/7/04] vs no).

• Phase I: Patients receive oral capecitabine twice daily on days 1-14 and vinorelbine IV over 6-10 minutes on days 1 and 8. Treatment repeats every 21 days for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of capecitabine and vinorelbine until the maximum tolerated dose (MTD) of each drug is determined. The MTD is defined as the dose at which 2 of 6 patients experience dose limiting toxicity.

• Phase II: Patients receive capecitabine and vinorelbine administered as in phase I, at the dose preceding the MTD.

Quality of life is assessed during phase II on days 1, 8, and 15 of course 1 and on day 1 of courses 2-4.

Patients are followed every 3 months until disease progression or start of any subsequent antitumor treatment.

PROJECTED ACCRUAL: A total of 98-110 patients will be accrued for this study.

• Drug: capecitabine
• Drug: vinorelbine ditartrate

• Hess D, Koberle D, Thurlimann B, Pagani O, Schonenberger A, Mattmann S, Rochlitz C, Rauch D, Schuller JC, Ballabeni P, Ribi K. Capecitabine and Vinorelbine as First-Line Treatment in Elderly Patients (>/=65 Years) with Metastatic Breast Cancer. A Phase II Trial (SAKK 25/99). Oncology. 2008 Apr 17;73(3-4):228-237 [Epub ahead of print]
• Hess D, Thurlimann B, Pagani O, Aebi S, Rauch D, Ballabeni P, Rufener B, Castiglione-Gertsch M, Goldhirsch A; Swiss Group of Clinical Cancer Research (SAKK). Capecitabine and vinorelbine in elderly patients (> or =65 years) with metastatic breast cancer: a phase I trial (SAKK 25/99). Ann Oncol. 2004 Dec;15(12):1760-5.

DISEASE CHARACTERISTICS:

• Histologically or cytologically proven adenocarcinoma of the breast
• Phase I: Measurable or evaluable disease
• Phase II: Bidimensionally measurable disease
• No CNS metastases

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age:

• 65 and over

Sex:

• Female

Menopausal status:

• Postmenopausal

Performance status:

• ECOG/SAKK 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Normal peripheral blood counts

Hepatic:

• AST no greater than 2 times upper limit of normal (ULN) (no greater than 3 times ULN if liver metastases present)

Renal:

• Creatinine no greater than 1.5 times ULN

Other:

• No other prior or concurrent malignancy except adequately treated basal or squamous cell skin cancer or carcinoma in situ of the cervix
• No peripheral neuropathy grade 2 or higher
• No cognitive impairment or severe psychiatric disorder

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• More than 6 months since prior adjuvant chemotherapy
• No prior chemotherapy for metastatic or locally advanced disease
• No other concurrent chemotherapy

Endocrine therapy:

• Prior hormonal therapy for metastatic disease allowed
• No continuous concurrent steroids
• No concurrent systemic endocrine therapy for breast cancer
• No other concurrent endocrine therapy

Radiotherapy:

• No concurrent radiotherapy involving greater than 30% of bone marrow or mucosa
• Radiotherapy to nonindicator lesion allowed

Surgery:

• Not specified

Other:

• Bisphosphonates allowed if indicator lesion in nonbone site