盐酸厄洛替尼和盐酸伊立替康治疗晚期实体瘤患者

Inclusion Criteria:

• Histologically confirmed malignancy that overexpresses epidermal growth factor receptor (EGFR)
• Unresectable disease for which there is no known standard therapy that ispotentially curative or definitely capable of extending life expectancy
• UGT1A1 genotype 6/6, 6/7, or 7/7
• Willing to provide biologic specimens
• Lesions amenable for 2 biopsies from the same tumor site (only patients receiving MTD in groups 2 and 3)
• No known brain metastases
• Performance status - ECOG 0-2
• At least 12 weeks
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9.0 g/dL
• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST ≤ 2.5 times ULN (5 times ULN if liver metastases present)
• Creatinine no greater than 1.5 times ULN
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• No New York Heart Association class III or IV heart disease
• No gastrointestinal tract disease resulting in an inability to take oral or nasogastric medication
• No requirement for IV alimentation
• No active peptic ulcer disease
• No abnormalities of the cornea (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 (e.g., Schirmer test or similar tear production test)
• No other uncontrolled concurrent illness
• No ongoing or active infection
• No significant traumatic injury within the past 21 days
• No seizure disorder
• No psychiatric illness or social situation that would preclude study compliance
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No concurrent grapefruit or grapefruit juice
• No smoking during study
• More than 4 weeks since prior immunotherapy or biologic therapy
• No concurrent immunotherapy
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• No other concurrent chemotherapy
• Not specified
• More than 4 weeks since prior radiotherapy
• No prior radiotherapy to more than 25% of bone marrow
• No concurrent radiotherapy
• More than 3 weeks since prior major surgery
• No prior surgical procedures affecting absorption
• No prior EGFR-targeting therapy (e.g., gefitinib or EKB-569)
• No other concurrent investigational therapy
• No concurrent enzyme-inducing anticonvulsants (e.g., phenytoin, phenobarbital, carbamazepine, or valproic acid)
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent enrollment on another study involving pharmacological agents for symptom control or therapeutic intent