Lapatinib Ditosylate and Capecitabine in Treating Patients With Stage IV Breast Cancer and Brain Metastases

Inclusion Criteria

• •DISEASE CHARACTERISTICS:
• •Histologically confirmed invasive breast cancer
• •* Stage IV disease
• •At least 1 measurable CNS lesion ≥ 10 mm on T1-weighted gadolinium-enhanced MRI
• •* No single brain metastasis that could be treated by surgery
• •HER-2 positive primary tumor as defined as IHC3+ or IHC2+ and FISH-positive
• •Hormone receptor status: not specified
• •PATIENT CHARACTERISTICS:
• •Menopausal status not specified
• •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• •Life expectancy ≥ 3 months
• •Absolute Neutrophil Count (ANC) ≥ 1,000/mm\^3
• •Platelet count ≥ 100,000/mm\^3
• •Hemoglobin ≥ 10g/dL
• •Creatinine ≥ 1.5 times upper limit of normal (ULN)
• •Albumin ≥ 2.5 g/dL
• •Serum bilirubin ≤ 1.5 times ULN (unless due to Gilbert's syndrome)
• •ASAT and ALAT ≤ 3 times ULN (≤ 5 times ULN with documented liver metastasis)
• •Not pregnant or nursing
• •Negative pregnancy test
• •Fertile patients must use effective contraception 2 weeks before, during, and for 28 days after completion of study treatment (female) or for 1 week after completion of treatment (male)
• •Able to swallow and retain oral medication
• •Affiliated to a Social Security System
• •No known contraindication to MRI
• •No prior or active malignancy, unless disease free for ≥ 10 years
• •No other concurrent severe and/or uncontrolled medical disease which could compromise study participation, including any of the following:
• •* Infection
• •* Cardiac disease (e.g., uncontrolled hypertension, congestive cardiac failure, ventricular arrhythmias, active ischemic heart disease, myocardial infarction within the past year, Left Ventricular EJection Fraction (LVEF) \> grade 2)
• •* Current active hepatic or biliary disease (except for Gilbert syndrome, asymptomatic gallstones, liver metastasis or stable chronic liver disease per investigator assessment)
• •* Renal disease
• •* Active gastrointestinal (GI) tract ulceration, malabsorption syndrome, active uncontrolled ulcerative colitis, or disease significantly affecting GI function
• •* Severely impaired lung function (e.g., spirometry and diffusion capacity of lung for carbon monoxide (DLCO) ≤ 50% of normal, and O\_2 saturation ≤ 88% at rest on room air)
• •No known dihydropyrimidine dehydrogenase deficiency
• •No significantly altered mental status prohibiting the understanding of the study, or with psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
• •Not deprived of liberty or placed under the authority of a tutor
• •PRIOR CONCURRENT THERAPY:
• •At least 2 weeks since prior breast cancer treatment (e.g., trastuzumab, chemotherapy, immunotherapy or biological response modifiers, endocrine therapy, or radiotherapy)
• •More than 30 days since prior investigational drugs
• •More than 14 days since prior and no concurrent strong inhibitors or inducers of the cytochrome P450 isoenzyme 3A4 (CYP3A4) (i.e., clarithromycin, ketoconazole, itraconazole, voriconazole, ritonavir)
• •No prior whole brain radiotherapy (WBRT) or brain stereotactic radiotherapy
• •No prior treatment with capecitabine and/or lapatinib ditosylate
• •No prior resection of the stomach or small bowel
• •No concurrent systemic treatment or radiation therapy for breast cancer (except corticosteroid, bisphosphonates, or mannitol)