S0635: Erlotinib and Bevacizumab in Stage IIIB and IV Bronchioloalveolar Carcinoma

Inclusion Criteria

• •DISEASE CHARACTERISTICS:
• •Biopsy-proven\* bronchioloalveolar carcinoma (BAC) or BAC variants (e.g., adenocarcinoma with BAC features, BAC with invasive adenocarcinoma) meeting the following criteria:
• •* Incompletely resected or unresectable disease
• •* No component of squamous cell carcinoma
• •* Disease staged as 1 of the following:
• •* Stage IIIB disease (T4 \[cytologically confirmed malignant pleural effusion OR pleural tumor foci that are separate from direct pleural invasion by the primary tumor\], any N, M0)
• •* Stage IV disease (any T, any N, M1 \[distant metastases present\])
• •* Recurrent disease in a separate lobe after prior resection within the past 5 years; multifocal lesions in \> 1 lobe; or any disease that is recurrent after surgery or radiotherapy is considered stage IV disease
• •* Tumor may be multifocal or diffuse NOTE: \*Cytology specimens, including bronchial brushing, washings, or fine needle aspiration specimens, alone are not acceptable for diagnosis
• •Measurable or nonmeasurable disease by chest CT scan
• •* Pleural effusions, ascites, and laboratory parameters are not acceptable as only evidence of disease
• •* Disease must be present outside field of prior radiotherapy OR a new lesion must be inside port
• •Treated brain metastases allowed provided the patient is asymptomatic and do not require steroids
• •PATIENT CHARACTERISTICS:
• •Zubrod performance status 0-2
• •Absolute neutrophil count ≥ 1,500/mm³
• •Platelet count ≥ 100,000/mm³
• •Total bilirubin normal
• •AST or AST ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
• •Alkaline phosphatase ≤ 2.5 times ULN (5 times ULN if bone metastases are present)
• •Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 50 mL/min
• •Urine protein:creatinine ratio ≤ 0.5 OR urine protein \< 1 g by 24-hour urine collection
• •Willing to provide prior smoking history
• •No hemoptysis ≥ ½ teaspoon within the past 28 days
• •No clinical history of pulmonary or upper respiratory hemorrhage \> grade 2 within the past 6 months or \> grade 1 within the past 28 days
• •No history of thromboses or hemorrhage, including hemorrhagic or thrombotic stroke, or other CNS bleeding
• •No uncontrolled hypertension
• •No serious nonhealing wound, ulcer, or bone fracture
• •No other prior malignancy except for any of the following:
• •* Adequately treated basal cell or squamous cell skin cancer
• •* In situ cervical cancer
• •* Adequately treated stage I or II cancer that is currently in complete remission
• •* Any other cancer from which the patient has been disease free for 5 years
• •Not pregnant or nursing
• •Fertile patients must use effective contraception
• •PRIOR CONCURRENT THERAPY:
• •See Disease Characteristics
• •Recovered from prior therapy
• •At least 28 days since prior radiotherapy (14 days for palliative radiotherapy)
• •At least 28 days since prior surgery (thoracic or other major surgeries)
• •More than 7 days since prior fine-needle aspiration or core biopsy
• •At least 28 days since prior systemic chemotherapy or biologic therapy
• •No prior gefitinib hydrochloride, erlotinib hydrochloride, or bevacizumab
• •No other prior anti-epidermal growth factor receptor or anti-vascular endothelial growth factor therapies
• •Concurrent stable, therapeutic anticoagulation therapy allowed (i.e., warfarin or low molecular weight heparin), provided the patient has no history of bleeding complications on anticoagulation or an inability to establish a stable therapeutic regimen for anticoagulation
• •No other concurrent anticancer therapy, including surgery, chemotherapy, hormone therapy, biologic therapy, or radiotherapy