Gemcitabine and R115777 (Tipifarnib) Combination Therapy for Metastatic Breast Cancer

Inclusion Criteria

Criteria:

- No more than 2 prior chemotherapy regimens for metastatic breast cancer

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No other concurrent investigational agents

- No other concurrent anticancer therapy

- Concurrent bisphosphonates allowed for bone metastases

- Histologically confirmed breast cancer:

- Clinical evidence of metastatic disease

- Measurable disease:

- At least 1 unidimensionally measurable lesion > 20 mm by conventional techniques
OR > 10 mm by spiral CT scan

- No known brain metastases and/or leptomeningeal disease

- No symptomatic lymphangitic pulmonary metastases

- Hormone receptor status:

- Not specified

- Menopausal status:

- Not specified

- Performance status:

- ECOG 0-2 OR Karnofsky 70-100%

- Hematopoietic:

- WBC >= 3,000/mm3

- Absolute neutrophil count >= 1,500/mm3

- Platelet count >= 100,000/mm3

- Hepatic:

- Bilirubin normal

- AST or ALT =< 2.5 times upper limit of normal

- Renal:

- Creatinine normal OR creatinine clearance >= 60 mL/min

- Cardiovascular:

- No symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No history of allergic reaction attributed to compounds of similar chemical or
biologic composition to tipifarnib or imidazole derivatives (e.g., clotrimazole,
ketoconazole, miconazole, or econazole)

- No peripheral neuropathy >= grade 2

- No ongoing or active infection

- No psychiatric illness or social situation that would preclude study compliance

- Prior trastuzumab (Herceptin) allowed

- No prior gemcitabine for metastatic breast cancer

- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
and recovered

- Prior hormonal therapy for stage IV disease and/or as adjuvant therapy allowed

- No prior localized radiotherapy to a single evaluable lesion

- No prior farnesyltransferase inhibitors for metastatic breast cancer

- No other uncontrolled illness

- No other malignancy within the past 5 years except curatively treated nonmelanoma
skin cancer or carcinoma in situ of the cervix

- More than 4 weeks since prior radiotherapy and recovered

Exclusion Criteria:

- central nervous system metastases

- congestive heart failure

- performance status 3

- performance status 4