A Phase II Study of Neoadjuvant Therapy With Docetaxel, Carboplatin, and Bevacizumab in Patients With Resectable Early Stage Non-Small Cell Lung Cancer
A Phase II Study of Neoadjuvant Therapy With Docetaxel, Carboplatin, and Bevacizumab in Patients With Resectable Early Stage Non-Small Cell Lung Cancer
RATIONALE: Drugs used in chemotherapy, such as docetaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving docetaxel and carboplatin together with bevacizumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
PURPOSE: This phase II trial is studying how well giving docetaxel and carboplatin together with bevacizumab works in treating patients with stage I, stage II, or stage III non-small cell lung cancer that can be removed by surgery.
OBJECTIVES:
Primary
Secondary
OUTLINE: Patients receive docetaxel IV over 15-60 minutes, carboplatin IV over 30-60 minutes, and bevacizumab* IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Approximately 4-6 weeks after completion of chemotherapy, eligible patients with no distant or mediastinal disease progression undergo lobectomy, pneumonectomy, or segmentectomy with standard radical mediastinal lymph node dissection.
NOTE: *Bevacizumab is only administered during courses 1 and 2.
After completion of study treatment, patients are followed periodically for 8 years.
PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.
DISEASE CHARACTERISTICS:
Histologically confirmed non-small cell lung cancer
Resectable stage IB-IIIA disease
No CNS or brain metastases
PATIENT CHARACTERISTICS:
ECOG performance status 0-1
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Hemoglobin ≥ 8.0 g/dL
Bilirubin normal
Creatinine ≤ 1.5 mg/dL
Urine protein:creatinine < 1.0
Alkaline phosphatase (AP), AST, and ALT must meet 1 of the following criteria:
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for at least 3 months after completion of study treatment
Adequate pulmonary and cardiovascular function to tolerate surgical resection
No cavitation or history of hemoptysis (i.e., bright red blood ≥ ½ teaspoon)
No existing peripheral neuropathy ≥ grade 1
No known history of severe hypersensitivity reaction to drugs formulated with polysorbate 80
No history of serious systemic disease, including any of the following:
Myocardial infarction within the past 6 months
Uncontrolled hypertension (i.e., blood pressure > 150/110 mm Hg on medication)
Unstable angina
New York Heart Association class II-IV congestive heart failure
Unstable symptomatic arrhythmia requiring medication
Clinically significant peripheral vascular disease (i.e., grade II or higher)
No history of significant neurological or psychiatric condition
No known active infection within the past 14 days
No serious, nonhealing wound, ulcer, or bone fracture
No evidence of bleeding diathesis or coagulopathy
No stroke within the past 6 months
No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
No other serious illness or medical condition
No active infection
No other currently active malignancy except nonmelanoma skin cancer
PRIOR CONCURRENT THERAPY: