Cisplatin, Vinorelbine, and Radiation Therapy in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery

OBJECTIVES:

Primary

• Compare the overall survival of patients with stage III non-small cell cancer treated with chemotherapy comprising cisplatin and vinorelbine ditartrate (CV) followed by radical radiotherapy versus concurrent CV chemoradiotherapy followed by CV chemotherapy.

Secondary

• Compare the progression-free survival of patients treated with these regimens.
• Compare the local progression-free survival (local control).
• Compare the hematological, pulmonary, esophageal, and neurological toxicities.
• Compare the response.
• Compare the quality of life.
• Compare the cost-effectiveness.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to clinically important factors. Patients are randomized to 1 of 2 treatment arms.

• Arm I (sequential treatment): Patients receive cisplatin IV over 2 hours on day 1 and vinorelbine ditartrate IV over 5-10 minutes on days 1 and 8. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Beginning in week 15, patients undergo radiotherapy 5 days a week for 4 weeks.
• Arm II (concurrent treatment): Patients undergo radiotherapy as in arm I beginning in week 1. Patients receive cisplatin IV over 2 hours on days 1-4 and vinorelbine ditartrate IV over 5-10 minutes on days 1 and 8. Chemotherapy repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, monthly for 6 months, and then at each follow-up visit.

After completion of study treatment, patients are followed periodically.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 508 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed stage III non-small cell lung cancer (NSCLC)

• Patients with stage IIIB disease must not have a pleural effusion that is cytologically proven to be malignant
• Inoperable disease
• Disease must be able to be encompassed within a radical radiotherapy treatment volume

PATIENT CHARACTERISTICS:

• ECOG performance status 0 or 1
• Life expectancy > 3 months
• Patient considered able to tolerate platinum-based chemotherapy and radical radiotherapy
• Glomerular filtration rate ≥ 60 mL/min
• WBC > 3,000/mm³
• Absolute neutrophil count > 1,500/mm³
• Hemoglobin > 10.0 g/dL

• Patients with hemoglobin between 10 and 12 g/dL at randomization require a blood transfusion to ensure hemoglobin > 12 g/dL before starting radiotherapy
• Platelet count > 100,000/mm³
• FEV_1 ≥ 1.0 L or DLCO (transfer factor) ≥ 50% of predicted
• Alkaline phosphatase ≤ 1.5 times upper limit of normal (ULN)
• Gamma-glutamyl-transferase < 1.5 times ULN
• Transaminases ≤ 1.5 times ULN
• Bilirubin ≤ 1.5 times ULN
• No medically unstable conditions (e.g., unstable diabetes, uncontrolled arterial hypertension, infection, hypercalcemia, or ischemic heart disease)
• Not pregnant or nursing
• Fertile patients must agree to use effective contraception
• Negative pregnancy test
• No other previous or current malignant disease likely to interfere with protocol treatment or comparisons

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy, radiotherapy, or investigational agents