• Objective response rate [ Designated as safety issue: No ]
• Overall survival [ Designated as safety issue: No ]
• Toxicity [ Designated as safety issue: Yes ]

• Objective response rate
• Overall survival
• Toxicity

RATIONALE: Drugs used in chemotherapy, such as cisplatin and etoposide, work in different ways to stop tumor cells from dividing so they stop growing or die. 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 deliver tumor-killing substances to them. Giving chemotherapy with a monoclonal antibody may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving cisplatin and etoposide together with bevacizumab works in treating patients with previously untreated extensive-stage small cell lung cancer.

OBJECTIVES:

Primary

• Determine the 6-month progression-free survival of patients with previously untreated extensive stage small cell lung cancer treated with cisplatin, etoposide, and bevacizumab.
• Determine the 6-month survival and response rate in patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.

Secondary

• Correlate pretreatment plasma levels of vascular endothelial growth factor (VEGF) with response and progression-free and overall survival of patients treated with this regimen.
• Correlate elevated plasma levels of endothelial cell-specific proteins (VCAM, E-selectin) with response in patients treated with this regimen.
• Correlate pre- and post-treatment plasma levels of basic fibroblast growth factor with response and progression-free and overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

• Chemotherapy: Patients receive cisplatin IV over 30-60 minutes on day 1 and etoposide IV over 60 minutes on days 1-3. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
• Bevacizumab therapy: Beginning concurrently with chemotherapy, patients receive bevacizumab IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 17 courses (1 year) in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months for up to 3 years from study entry.

PROJECTED ACCRUAL: A total of 27-66 patients will be accrued for this study within 3-8 months.

• Biological: bevacizumab
• Drug: cisplatin
• Drug: etoposide

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed small cell lung cancer

  • Extensive stage disease

• Measurable disease

  • Previously irradiated lesions must not be the sole site of measurable disease
  • No prior radiotherapy to the site of evaluable disease
• No CNS metastases by CT scan or MRI within the past 4 weeks

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• No history of hemorrhagic disorders

Hepatic

• Bilirubin ≤ 1.5 mg/dL
• PTT ≤ upper limit of normal
• INR ≤ 1.5

Renal

• Creatinine ≤ 1.5 mg/dL

• Proteinuria < 1+

  • For proteinuria ≥ 1+, urine protein must be ≤ 1 g/24 hours

Cardiovascular

• No symptomatic congestive heart failure
• No cardiac arrhythmia
• No history of thrombotic disorders
• No clinically significant peripheral artery disease

• No arterial thromboembolic event within the past 6 months, including any of the following:

  • Transient ischemic attack
  • Cerebrovascular accident
  • Unstable angina
  • Myocardial infarction
• Hypertension must be well-controlled (≤ 150/85) on a stable regimen of antihypertensive therapy

Pulmonary

• No history of gross hemoptysis (i.e., ≥ 1 teaspoon of bright red blood)

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study treatment
• No other malignancy within the past 5 years except cured basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No serious nonhealing wound, ulcer, or bone fracture

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior immunotherapy for lung cancer
• No prior biologic therapy for lung cancer

Chemotherapy

• No prior chemotherapy for lung cancer

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• No concurrent local radiotherapy for pain control or life-threatening situations

Surgery

• More than 28 days since prior major surgery
• More than 7 days since prior minor surgery or needle biopsies

Other

• No concurrent chronic daily aspirin (> 325 mg/day)
• No concurrent nonsteroidal anti-inflammatory agents known to inhibit platelet function

• No concurrent therapeutic anticoagulation

  • Prophylactic anticoagulation of venous access devices is allowed

• No concurrent treatment with any of the following:

  • Dipyridamole
  • Ticlopidine
  • Clopidogrel
  • Cilostazol