OBJECTIVES:

• Determine the maximum tolerated dose of erlotinib in patients with solid tumors and hepatic or renal dysfunction.
• Determine the pharmacokinetics of this drug in these patients.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to hepatic or renal dysfunction (albumin less than 2.5 g/dL, direct bilirubin less than 1.0 mg/dL, any AST, and creatinine normal vs direct bilirubin 1.0-7.0 mg/dL, any AST, and creatinine normal vs creatinine 2.5-5.0 mg/dL, albumin 2.5 g/dL or greater, AST less than 3 times upper limit of normal, and direct bilirubin less than 1.0 mg/dL).

Patients receive oral erlotinib once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, at least 6 evaluable patients are treated at that dose.

PROJECTED ACCRUAL: A maximum of 75 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed solid tumor, including gliomas and the following epithelial malignancies:

  • Non-small cell lung
  • Mesothelioma
  • Breast
  • Head and neck
  • Esophageal
  • Pancreatic
  • Bladder
  • Prostate
  • Ovarian
  • Anal
  • Colorectal carcinoma
  • Cervical carcinoma
  • Hepatocellular carcinoma
• Metastatic or unresectable disease
• Standard curative or palliative therapy does not exist or is no longer effective
• Epidermal growth factor receptor (EGFR) positive

• Hepatic or renal dysfunction defined as one of the following:

  • Direct bilirubin 1.0-7.0 mg/dL with any AST
  • Albumin less than 2.5 g/dL
  • Creatinine 2.5-5.0 mg/dL
• Brain metastases allowed provided patient is asymptomatic, previously treated, has stable disease for at least 2 months, and is not currently receiving steroid therapy

• 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:

• Not specified

Hematopoietic:

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

Hepatic:

• See Disease Characteristics
• No evidence of biliary obstruction

Renal:

• See Disease Characteristics
• No evidence of renal obstruction

Cardiovascular:

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Gastrointestinal:

• No gastrointestinal tract disease that would preclude ability to take oral medications
• No requirement for IV alimentation
• No active peptic ulcer disease

Ophthalmic:

• No prior corneal abnormalities (e.g., dry eye syndrome or Sjogren's syndrome)
• No prior congenital abnormality (e.g., Fuch's dystrophy)
• No prior abnormal slit-lamp exam using a vital dye (e.g., fluorescein or Bengal-Rose)
• No prior abnormal corneal sensitivity test (e.g., Schirmer test or similar tear production test)

Other:

• No other concurrent uncontrolled illness
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF)

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for melphalan or mitomycin)
• No prior nitrosoureas

Endocrine therapy:

• See Disease Characteristics
• No concurrent steroids

Radiotherapy:

• At least 4 weeks since prior radiotherapy

Surgery:

• At least 4 weeks since prior major surgery
• No prior surgical procedures affecting absorption

Other:

• No prior EGFR-targeting therapies, including gefitinib or Imclone C-225
• At least 3 months since prior suramin
• More than 7 days since prior grapefruit juice
• More than 7 days since other prior CYP3A4 inhibitors
• No concurrent grapefruit juice
• No concurrent CYP3A4 inducers, substrates, or other inhibitors
• No concurrent medications known to affect hepatic or renal function, including antiseizure medication or nonsteroidal anti-inflammatory agents
• No concurrent combination anti-retroviral therapy for HIV-positive patients