Vinorelbine, Gemcitabine, and Docetaxel Compared With Paclitaxel and Carboplatin in Treating Patients With Advanced Non-Small Cell Lung Cancer

OBJECTIVES:

Primary

• Compare the therapeutic effect of vinorelbine, gemcitabine, and docetaxel vs paclitaxel and carboplatin in patients with advanced non-small cell lung cancer.
• Compare the overall survival of patients treated with these regimens.

Secondary

• Compare the response rate in patients treated with these regimens.
• Compare the toxicity of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive vinorelbine IV and gemcitabine IV on days 1 and 8. Treatment repeats every 21 days for 3 courses. Patients then receive docetaxel IV on day 1. Treatment repeats every 21 days for 3 courses.
• Arm II: Patients receive carboplatin IV and paclitaxel IV on day 1. Treatment repeats every 21 days for 6 courses.

Patients are followed for 1 year.

PROJECTED ACCRUAL: A total of 400 patients (200 per treatment arm) will be accrued for this study within 2 years.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed primary non-small cell lung cancer (NSCLC) meeting criteria for 1 of the following:

• Newly diagnosed selected stage IIIB (T4 lesion due to malignant pleural effusion) disease
• Newly diagnosed stage IV disease
• Recurrent disease after prior surgery and/or radiotherapy
• The following cellular subtypes are allowed:

• Adenocarcinoma
• Large cell carcinoma
• Squamous cell carcinoma
• Unspecified carcinoma
• Measurable or nonmeasurable disease by CT scan, MRI, x-ray, physical examination, or bone scintigraphy

• Pleural effusions, ascites, and laboratory parameters are not allowed as the only evidence of disease
• Disease must be present outside area of prior surgical resection
• Disease must be present outside area of prior radiotherapy OR new lesion documented
• No known brain metastases by CT scan or MRI within the past 6 weeks
• No pleural or pericardial effusions requiring treatment

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9 g/dL

Hepatic

• Bilirubin ≤ 2 times upper limit of normal (ULN)
• SGOT or SGPT ≤ 2 times ULN
• Alkaline phosphatase ≤ 2 times ULN

Renal

• Creatinine ≤ ULN
• Creatinine clearance ≥ 50 mL/min

Cardiovascular

• No uncontrolled hypertension
• No unstable angina
• No congestive heart failure
• No myocardial infarction within the past year
• No ventricular arrhythmia requiring medical intervention

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No prior allergic drug reaction attributed to Cremophor or polysorbate 80
• No disorder associated with lung cancer with life-threatening consequences
• No motor or sensory neuropathy ≥ grade 2
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission
• No uncontrolled diabetes

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior biologic therapy for NSCLC

Chemotherapy

• No prior systemic chemotherapy for NSCLC

Endocrine therapy

• No prior or concurrent steroid-type hormonal therapy (e.g., ethinyl estradiol)

Radiotherapy

• See Disease Characteristics
• At least 3 weeks since prior radiotherapy and recovered

Surgery

• See Disease Characteristics
• At least 2 weeks since prior thoracic or other major surgery and recovered

Other

• No prior or concurrent azole antifungal therapy (e.g., ketoconazole, miconazole, or itraconazole)
• No prior or concurrent macrolides (e.g., erythromycin or clarithromycin)
• No prior or concurrent cyclosporine, terfenadine, benzodiazepines (e.g., diazepam, triazolam, or midazolam), or retinoids
• No prior or concurrent calcium antagonists (e.g., diltiazem, nifedipine, or verapamil)