Erlotinib and Gemcitabine in Treating Patients With Metastatic Breast Cancer Previously Treated With An Anthracycline and/or a Taxane

OBJECTIVES:

- Determine the anti-tumor activity of erlotinib and gemcitabine in patients with
metastatic breast cancer previously treated with anthracycline and/or taxane.

- Determine the adverse event profile of this regimen in these patients.

- Determine whether epidermal growth factor receptor and HER-2 receptor intensity and
serum concentrations have an impact on clinical response in patients treated with this
regimen.

- Determine the impact of genetic differences in proteins involved in drug response
(transport, metabolism, and mechanism of action) on clinical response and adverse
events associated with gemcitabine in these patients.

OUTLINE: This is a multicenter study.

Patients receive gemcitabine IV on days 1 and 8 and oral erlotinib on days 1-21. Courses
repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients achieving a complete response are followed every 6 weeks for up to 5 years or until
disease progression (PD). Patients discontinuing study therapy for any other reason are
followed every 3 months until PD and then every 6 months for up to 5 years.

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed breast cancer

- Clinical evidence of metastatic disease

- Candidate for first- or second-line chemotherapy for metastatic disease

- Must have received prior anthracycline or taxane therapy (may have had both in the
neoadjuvant, adjuvant, or metastatic setting)

- At least 1 measurable lesion at least 20 mm by CT scan or MRI OR at least 10 mm by
spiral CT scan

- The following are not considered measurable disease:

- Small lesions less than 20 mm by CT scan or MRI

- Bone lesions

- Ascites

- Pleural/pericardial effusion

- Inflammatory breast disease

- Lymphangitis cutis/pulmonis

- Abdominal masses not confirmed and followed by imaging techniques

- Cystic lesions

- No active CNS metastases (treated CNS metastases stable for more than 8 weeks are
allowed)

- Hormone receptor status:

- Not specified

PATIENT CHARACTERISTICS:

Age

- 18 and over

Sex

- Male or female

Menopausal status

- Not specified

Performance status

- ECOG 0-2

Life expectancy

- At least 3 months

Hematopoietic

- Absolute neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- Hemoglobin at least 8.5 g/dL

Hepatic

- Bilirubin no greater than 1.5 times upper limit of normal (ULN)

- AST no greater than 3 times ULN

- Alkaline phosphatase no greater than 3 times ULN

Renal

- Creatinine no greater than 1.5 times ULN

Cardiovascular

- No symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia

Gastrointestinal

- No inability to take oral or nasogastric medication

- No requirement for IV alimentation

- No active peptic ulcer disease

Ophthalmic

- No abnormalities of the cornea based on history (e.g., dry eye syndrome or Sjögren's
syndrome)

- No congenital abnormality (e.g., Fuch's dystrophy)

- No abnormal slit-lamp examination using a vital dye (e.g., fluorescein or
Bengal-Rose)

- No abnormal corneal sensitivity test (Schirmer test or similar tear production test)

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Sub-dermal implants and condoms are not considered acceptable forms of
contraception

- No other invasive non-breast malignancy within the past 5 years except adequately
treated basal cell or squamous cell skin cancer

- No ongoing or active infection

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

- No other concurrent uncontrolled illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

- At least 2 weeks since prior immunotherapy

- No prior cetuximab

Chemotherapy

- At least 2 weeks since prior chemotherapy and recovered

- No more than 1 prior chemotherapy regimen for metastatic disease

- No more than 2 prior chemotherapy regimens total, including adjuvant therapy

Endocrine therapy

- Prior hormonal therapy allowed in metastatic and/or adjuvant setting

Radiotherapy

- At least 2 weeks since prior radiotherapy

- No prior radiotherapy to more than 25% of bone marrow

- No prior strontium chloride Sr 89

Surgery

- More than 4 weeks since prior major surgery

- No prior surgical procedures affecting absorption

Other

- No prior epidermal growth factor receptor-targeting therapies (e.g., gefitinib or
EKB-569)

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No other concurrent antitumor therapy