RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known if combination chemotherapy is more effective than no further treatment for non-small cell lung cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of vinorelbine plus cisplatin with that of no further therapy in treating patients who have stage I or stage II non-small cell lung cancer that has been completely removed during surgery.

OBJECTIVES: I. Compare the duration of overall and disease-free survival in patients with completely resected non-small cell lung cancer (NSCLC) randomized to adjuvant chemotherapy with vinorelbine and cisplatin versus observation only. II. Confirm the prognostic significance of ras mutations when present in the primary tumor. III. Provide a comprehensive tumor bank linked to a clinical database for the further study of molecular markers in resected NSCLC. IV. Measure and compare the health-related quality of life of patients on both treatment arms. V. Evaluate any toxicity related to this treatment regimen.

OUTLINE: This is a randomized study. Patients are stratified according to participating institution, nodal status (N0 vs N1), and ras mutation status of primary tumor (absent vs present vs unknown). Patients are randomized to one of two treatment arms. Arm I: Patients are evaluated at 3 and 6 months after randomization. Arm II: Patients receive vinorelbine IV over 6-10 minutes weekly for 16 weeks. Patients also receive cisplatin IV on days 1 and 8 every 4 weeks for a total of 4 courses. Treatment continues in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at Canadian centers. Quality of life assessments are optional for ECOG and SWOG centers. Patients are followed every 3 months for 2 years and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 450 patients will be accrued for this study within 6.75 years.

• Drug: cisplatin
• Drug: vinorelbine ditartrate

• Bezjak A, Lee CW, Ding K, Brundage M, Winton T, Graham B, Whitehead M, Johnson DH, Livingston RB, Seymour L, Shepherd FA. Quality-of-life outcomes for adjuvant chemotherapy in early-stage non-small-cell lung cancer: results from a randomized trial, JBR.10. J Clin Oncol. 2008 Nov 1;26(31):5052-9. Epub 2008 Sep 22.
• Gauthier I, Ding K, Winton T, Shepherd FA, Livingston R, Johnson DH, Rigas JR, Whitehead M, Graham B, Seymour L. Impact of hemoglobin levels on outcomes of adjuvant chemotherapy in resected non-small cell lung cancer: The JBR.10 trial experience. Lung Cancer. 2007 Mar;55(3):357-363. Epub 2006 Dec 1.
• Pepe C, Hasan B, Winton TL, Seymour L, Graham B, Livingston RB, Johnson DH, Rigas JR, Ding K, Shepherd FA; National Cancer Institute of Canada and Intergroup Study JBR.10. Adjuvant vinorelbine and cisplatin in elderly patients: National Cancer Institute of Canada and Intergroup Study JBR.10. J Clin Oncol. 2007 Apr 20;25(12):1553-61.
• Seve P, Lai R, Ding K, Winton T, Butts C, Mackey J, Dumontet C, Dabbagh L, Aviel-Ronen S, Seymour L, Whitehead M, Tsao MS, Shepherd FA, Reiman T. Class III beta-tubulin expression and benefit from adjuvant cisplatin/vinorelbine chemotherapy in operable non-small cell lung cancer: analysis of NCIC JBR.10. Clin Cancer Res. 2007 Feb 1;13(3):994-9.
• Alam N, Shepherd FA, Winton T, Graham B, Johnson D, Livingston R, Rigas J, Whitehead M, Ding K, Seymour L. Compliance with post-operative adjuvant chemotherapy in non-small cell lung cancer. An analysis of National Cancer Institute of Canada and intergroup trial JBR.10 and a review of the literature. Lung Cancer. 2005 Mar;47(3):385-94. Review. Erratum in: Lung Cancer. 2005 Nov;50(2):283-4.
• Winton T, Livingston R, Johnson D, Rigas J, Johnston M, Butts C, Cormier Y, Goss G, Inculet R, Vallieres E, Fry W, Bethune D, Ayoub J, Ding K, Seymour L, Graham B, Tsao MS, Gandara D, Kesler K, Demmy T, Shepherd F; National Cancer Institute of Canada Clinical Trials Group; National Cancer Institute of the United States Intergroup JBR.10 Trial Investigators. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med. 2005 Jun 23;352(25):2589-97.
• Asmis TR, Ding K, Seymour L, Shepherd FA, Leighl NB, Winton TL, Whitehead M, Spaans JN, Graham BC, Goss GD; National Cancer Institute of Canada Clinical Trials Group. Age and comorbidity as independent prognostic factors in the treatment of non small-cell lung cancer: a review of National Cancer Institute of Canada Clinical Trials Group trials. J Clin Oncol. 2008 Jan 1;26(1):54-9.
• Kassam F, Shepherd FA, Johnston M, Visbal A, Feld R, Darling G, Keshavjee S, Pierre A, Waddell T, Leighl NB. Referral patterns for adjuvant chemotherapy in patients with completely resected non-small cell lung cancer. J Thorac Oncol. 2007 Jan;2(1):39-43.
• Ng R, Hasan B, Mittmann N, Florescu M, Shepherd FA, Ding K, Butts CA, Cormier Y, Darling G, Goss GD, Inculet R, Seymour L, Winton TL, Evans WK, Leighl NB; Working Group on Economic Analysis; Lung Disease Site Group; National Cancer Institute of Canada Clinical Trials Group. Economic analysis of NCIC CTG JBR.10: a randomized trial of adjuvant vinorelbine plus cisplatin compared with observation in early stage non-small-cell lung cancer--a report of the Working Group on Economic Analysis, and the Lung Disease Site Group, National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007 Jun 1;25(16):2256-61.
• Hotta K, Matsuo K, Kiura K, Ueoka H, Tanimoto M. Advances in our understanding of postoperative adjuvant chemotherapy in resectable non-small-cell lung cancer. Curr Opin Oncol. 2006 Mar;18(2):144-50. Review.
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• Visbal AL, Leighl NB, Feld R, Shepherd FA. Adjuvant Chemotherapy for Early-Stage Non-small Cell Lung Cancer. Chest. 2005 Oct;128(4):2933-43. Review.

DISEASE CHARACTERISTICS: Histologically confirmed primary non-small cell lung cancer that is completely resected No mixed small and non-small cell histologies Pathologic T2 N0 or T1-2 N1 T1 N1 and T2 N1 only for CALGB institutions Removal of all gross disease with negative resection margins by lobectomy, sleeve resection, bilobectomy, or pneumonectomy (based on intraoperative findings) No segmentectomy or wedge resection Complete mediastinal lymph node resection or sampling required at primary tumor resection, with minimum levels of nodal sampling as follows: Primary in right upper lobe - levels 4, 7, 10 Primary in right middle lobe - levels 4, 7, 10 Primary in right lower lobe - levels 4, 7, 9, 10 Primary in left upper lobe - levels 5, 6, 7, 10 Primary in left lower lobe - levels 7, 9, 10 If complete mediastinal lymph node resection has not been undertaken, any mediastinal lymph node which measured 1.5 cm or more on presurgical CT scan must have been biopsied and found to be free of metastatic involvement Disease at nodal station 10 (tracheobronchial angle) is considered N2 disease for this trial and is not eligible No more than one discrete primary tumor No bronchoalveolar carcinoma with lobar or multilobar involvement Discrete solitary radiological mass or nodule eligible Snap frozen fresh primary tumor tissue must be submitted to Lung Cancer Tumor Bank within 14 days after surgery by selected Canadian centers Others to submit representative paraffin block within 2 months of surgery

PATIENT CHARACTERISTICS: Age: 18 and over (lower age limit determined by individual center) Performance status: ECOG 0 or 1 Life expectancy: Not specified Hematopoietic: Absolute granulocyte count greater than 2,000/mm3 Platelet count greater than 100,000/mm3 Hemoglobin greater than 10.0 g/dL Hepatic: Bilirubin no greater than 1.25 times normal AST/ALT no greater than 1.25 times normal Alkaline phosphatase no greater than 1.25 times normal Renal: Creatinine no greater than 1.7 mg/dL Cardiovascular: No history of congestive heart failure or other cardiac abnormality that may preclude hydration necessary for cisplatin administration Other: No active pathologic condition that would preclude study No active uncontrolled infection No history of psychiatric or neurologic disorder that would preclude study No prior breast cancer, melanoma, or hypernephroma No other malignancy within the past 5 years except adequately treated nonmelanomatous skin cancer or carcinoma in situ of the cervix Not pregnant or nursing Fertile patients must use effective contraception Ability to tolerate treatment (based on consultation between the thoracic surgeon and a medical oncologist or hematologist) and available for follow-up

PRIOR CONCURRENT THERAPY: Complete resection required Randomization between 28 and 40 days after surgery required

• National Cancer Institute (NCI)
• Southwest Oncology Group
• Eastern Cooperative Oncology Group
• Cancer and Leukemia Group B