Bevacizumab, Cisplatin, Etoposide, and Radiation Therapy in Treating Patients With Limited-Stage Small Cell Lung Cancer

OBJECTIVES:

Primary

• Determine the 1-year progression-free survival of patients with limited-stage small cell lung cancer treated with bevacizumab, cisplatin, etoposide, and radiotherapy.

Secondary

• Determine the toxicity of this regimen in these patients.
• Determine the response rate in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive cisplatin IV over 30-60 minutes and bevacizumab IV over 30-90 minutes on day 1 and etoposide IV over 60 minutes on days 1-3. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. During course 1, patients also undergo thoracic radiotherapy twice daily on days 1-5, 8-12, and 15-19.

Patients achieving a complete or partial response or stable disease after the first 4 courses of chemotherapy continue to receive bevacizumab IV over 30-90 minutes on day 1. Treatment with bevacizumab repeats every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

Within 4-6 weeks after blood counts recover from the first 4 courses of chemotherapy, patients achieving a complete or partial response also undergo prophylactic cranial irradiation (PCI) in 10 fractions over 3 weeks.*

NOTE: *Bevacizumab should not be given for 3 weeks prior to or during PCI, but resumed 1 week after completion of PCI.

After completion of study treatment, patients are followed periodically for 10 years.

PROJECTED ACCRUAL: A total of 79 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed small cell lung cancer (SCLC)

• Limited-stage disease, defined as SCLC confined to ≥ 1 of the following:

• One hemithorax
• Ipsilateral supraclavicular fossa
• Measurable disease
• No malignant pleural effusion, contralateral hilar disease, or contralateral supraclavicular disease

• Minimal pleural effusion visible on CT scan of the chest, but not evident on chest x-ray, allowed
• No completely surgically resected disease
• No CNS disease, including primary brain tumor or brain metastasis

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Absolute granulocyte count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 1.5 mg/dL
• Creatinine ≤ 1.5 mg/dL
• Urine protein:creatinine ratio ≤ 0.5 OR 24-hour urine protein < 1,000 mg
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment
• INR ≤ 1.5 (unless on full-dose anticoagulants)
• No active serious infection
• No serious or nonhealing wound
• No ulcer or bone fracture
• No evidence of bleeding diatheses or coagulopathy
• No hemoptysis
• No known hypersensitivity to Chinese hamster ovary cell products and/or other recombinant human antibodies
• No clinically significant cardiovascular disease, including any of the following:

• Uncontrolled hypertension
• New York Heart Association class II-IV congestive heart failure
• Serious cardiac arrhythmia requiring medication
• Unstable angina pectoris
• Symptomatic peripheral vascular disease
• Cerebrovascular accident within the past 6 months
• Symptomatic heart disease within the past 6 months
• Myocardial infarction within the past 6 months
• Unstable angina within the past 6 months
• No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 4 weeks
• No significant traumatic injury within the past 4 weeks

PRIOR CONCURRENT THERAPY:

• At least 4 weeks since prior major surgery or open biopsy
• At least 1 week since prior core biopsy
• No prior chemotherapy or radiotherapy for small cell lung cancer
• No concurrent major surgery
• No concurrent palliative local radiotherapy
• No concurrent intensity-modulated radiotherapy
• Concurrent full-dose anticoagulants (e.g., warfarin) allowed provided all of the following criteria are met:

• INR ≤ 3
• In-range INR (2-3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin
• No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)