RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving a chemotherapy drug before surgery may shrink the tumor so that it can be removed during surgery. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known whether chemotherapy followed by surgery with or without radiation therapy is more effective than chemotherapy followed by radiation therapy alone in treating non-small cell lung cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy followed by surgery with or without radiation therapy to that of chemotherapy followed by radiation therapy alone in treating patients who have stage III non-small cell lung cancer.

Condition	Treatment or Intervention	Phase
Squamous Cell Lung Cancer large cell lung cancer stage IIIA non-small cell lung cancer Adenocarcinoma of the Lung Adenosquamous Cell Lung Cancer Bronchoalveolar Cell Lung Cancer	Drug: carboplatin  Drug: cisplatin  Procedure: chemotherapy  Procedure: conventional surgery  Procedure: radiation therapy  Procedure: surgery	Phase III

Further Study Details: 

OBJECTIVES:

• Compare the overall survival of patients with stage IIIA non-small cell lung cancer treated with surgery with or without radiotherapy versus radiotherapy alone after achieving a response to a neoadjuvant chemotherapy regimen containing cisplatin or carboplatin.
• Compare the progression-free survival of patients treated with these regimens.
• Compare the toxic effects of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, response to induction chemotherapy (complete vs partial vs minor), and histological subtype (squamous vs nonsquamous).

All patients receive 3 courses of induction combination chemotherapy comprising cisplatin or carboplatin in the absence of disease progression or unacceptable toxicity. Patients with complete or partial response (or minor response if disease has become resectable) are randomized to 1 of 2 treatment arms.

• Within 6 weeks of randomization, patients undergo radical lobectomy or pneumonectomy plus dissection of the hilar and mediastinal lymph nodes. Patients with positive resection margins of at least 1 cm and/or positive mediastinal nodes undergo radiotherapy 5 days a week for 5.5 weeks.

Patients with postresection subclinical/microscopic disease with negative tumor margins undergo radiotherapy 5 days a week for 4-4.5 weeks.

• Within 6 weeks of randomization, patients undergo primary radiotherapy. Patients with subclinical/microscopic disease with negative tumor margins undergo radiotherapy 5 days a week for 4-4.5 weeks.

Patients with gross tumor volume and tumor margins at least 1 cm undergo radiotherapy 5 days a week for 6 weeks.

Patients are followed every 3 months for 2 years and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 640 patients will be accrued for this study within 8 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically proven primary unresectable non-small cell lung cancer (NSCLC) by mediastinoscopy, mediastinotomy, thoracotomy, video-assisted thoracic surgery, or needle biopsy
• Stage IIIA (N2) disease by chest CT scan
• Any histologic subtype allowed
• At least 1 unidimensionally or bidimensionally measurable target lesion on chest CT scan
• No N3 or metastatic disease by physical exam, CT scan of thorax, bone scan, and CT scan or ultrasound of liver and adrenals
• No pre-existing pleural or pericardial effusion
• No symptomatic CNS involvement

PATIENT CHARACTERISTICS: Age:

• Over 18

Performance status:

• WHO 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Cardiovascular:

• No superior vena cava syndrome

Pulmonary:

• No diffuse interstitial pulmonary fibrosis

Other:

• No prior melanoma, breast cancer, or hypernephroma
• No other primary malignancy within the past 5 years except adequately treated basal cell skin cancer or carcinoma in situ of the cervix
• No grade 2 or greater pre-existing motor or sensory neurotoxicity
• No active uncontrolled infection requiring IV antibiotics
• Must be physically and mentally fit for study therapy
• No psychological, familial, sociological, or geographical condition that would preclude study compliance
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy for NSCLC

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy for NSCLC

Surgery:

• No prior surgery for NSCLC

Other:

• No other prior therapy for NSCLC

Belgium
      A.Z. St. Jan, Brugge,  8000,  Belgium
      Algemeen Ziekenhuis Middelheim, Antwerp,  2020,  Belgium
      CHR - Clinique Saint Joseph - Hopital de Warqueguies, Mons,  B-7000,  Belgium
      Clinique Universitaire De Mont-Godinne, Mont-Godinne Yvoir,  5530,  Belgium
      Hopital de Jolimont, Haine-Saint-Paul,  7100,  Belgium
      Stedelijk Ziekenhuis, Roesclare,  8800,  Belgium
      U.Z. Gasthuisberg, Leuven,  B-3000,  Belgium
      Universitair Ziekenhuis Antwerpen, Edegem,  B-2650,  Belgium
France
      Academisch Ziekenhuis Utrecht, Vandoeuvre-les-Nancy,  54511,  France
Italy
      Istituto Nazionale per la Ricerca sul Cancro, Genoa (Genova),  16132,  Italy
Netherlands
      Antoni van Leeuwenhoekhuis, Amsterdam,  1066 CX,  Netherlands
      Arnhems Radiotherapeutisch Instituut, ARNHEM,  6815 AD,  Netherlands
      Atrium Medical Centre, HEERLEN,  6419 PC,  Netherlands
      Canisius-Wilhelmina Ziekenhuis, Nijmegen,  6532 SZ,  Netherlands
      Diakonessenhuis Utrecht, Utrecht,  3508 TG,  Netherlands
      Elkerliek Ziekenhuis, Helmond,  5707-HA,  Netherlands
      Erasmus Medical Center, Rotterdam,  3075 EA,  Netherlands
      Groot Ziekengasthuis 's-Hertogenbosch, 's-Hertogenbosch,  5211 NL,  Netherlands
      Leiden University Medical Center, Leiden,  2300 CA,  Netherlands
      Saint Franciscus Ziekenhuis, Roosendaal,  4708 AE,  Netherlands
      Sint Antonius Ziekenhuis, Nieuwegein,  3435 CM,  Netherlands
      Sophia Ziekehuis, Zwolle,  8000 GK,  Netherlands
      Twee Steden Ziekenhuis Vestiging Tilburg, Tilburg,  5042 AD,  Netherlands
      University Hospital - Rotterdam Dijkzigt, Rotterdam,  3000 CA,  Netherlands
      University Medical Center Nijmegen, Nijmegen,  NL-6500 HB,  Netherlands
      Vrije Universiteit Medisch Centrum, Amsterdam,  1001HV,  Netherlands
      Ziekenhuis St Jansdal, Harderwijk,  3840 AC,  Netherlands
United Kingdom, England
      Leicester Royal Infirmary, Leicester,  England,  LE1 5WW,  United Kingdom
      Royal Marsden Hospital, Sutton,  England,  SM2 5PT,  United Kingdom
United Kingdom, Northern Ireland
      Royal Victoria Hospital, Belfast,  Northern Ireland,  BT12 6BA,  United Kingdom

Study chairs or principal investigators

Ted A.W. Splinter, MD,  Study Chair,  University Hospital - Rotterdam Dijkzigt   

Study ID Numbers:  CDR0000063983; EORTC-08941
Record last reviewed:  April 2003
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002623
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08