Cisplatin and Docetaxel With or Without Radiation Therapy in Treating Patients Who Are Undergoing Surgery for Newly Diagnosed Stage III Non-Small Cell Lung Cancer
Condition: Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: filgrastim; pegfilgrastim; cisplatin; docetaxel; adjuvant therapy; conventional surgery; neoadjuvant therapy; radiation therapy
Intervention description: Consolidation chemotherapy; Consolidation chemotherapy
Intervention MeSH terms: Docetaxel
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage IIIA non-small cell lung cancer; adenocarcinoma of the lung; large cell lung cancer; squamous cell lung cancer; bronchoalveolar cell lung cancer

Summary:

      RATIONALE: Drugs used in chemotherapy, such as cisplatin and docetaxel, work in different
      ways to stop the growth of tumor cells, either by killing the cells or by stopping them from
      dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Cisplatin and
      docetaxel may make tumor cells more sensitive to radiation therapy. Giving more than one drug
      (combination chemotherapy) together with radiation therapy before surgery may shrink the
      tumor so it can be removed. Giving chemotherapy after surgery may kill any tumor cells that
      remain after surgery. It is not yet known whether giving cisplatin and docetaxel together
      with radiation therapy is more effective than giving cisplatin together with docetaxel in
      treating non-small cell lung cancer.

      PURPOSE: This randomized phase III trial is studying cisplatin, docetaxel, and radiation
      therapy to see how well they work compared to cisplatin and docetaxel in treating patients
      who are undergoing surgery for newly diagnosed stage III non-small cell lung cancer.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically or cytologically confirmed primary non-small cell lung cancer (NSCLC)*,
             including any of the following cellular types:

               -  Adenocarcinoma

               -  Squamous cell carcinoma

               -  Large cell carcinoma

               -  Non-lobar and non-diffuse bronchoalveolar cell carcinoma

               -  NSCLC not otherwise specified NOTE: *Diagnosed within the past 3 months;
                  diagnosis by mediastinal nodal biopsy or needle aspiration allowed provided a
                  distinct lung primary (separate from the nodes) is clearly evident on CT scan

          -  Stage IIIA disease

               -  T1-T3 disease

                    -  If pleural effusion is present, must meet ≥ 1 of the following criteria to
                       exclude T4 disease:

                         -  Pleural effusion cytologically negative by thoracentesis

                         -  Documented absence of pleural metastases and pleural effusion
                            cytologically negative by thoracoscopy (for patients with pleural
                            effusion on CT scan [but not on chest x-ray] that is deemed too small
                            to tap safely under either CT scan or ultrasound guidance)

               -  Confirmed positive ipsilateral mediastinal lymph node(s) (N2 disease)**, with or
                  without positive ipsilateral hilar nodes, by mediastinoscopy, mediastinotomy,
                  endoscopic ultrasound-guided transesophageal biopsy, thoracotomy, video-assisted
                  thoracoscopy, Wang needles, or fine needle aspiration under bronchoscopic or CT
                  guidance

                    -  N2 nodes must be separate from primary tumor by CT scan or surgical
                       exploration AND maximum diameter ≤ 3.0 cm

                    -  Mediastinoscopy OR other means of mediastinal lymph node biopsy required
                       (regardless of the primary tumor site) for patients with subcarinal
                       lymphadenopathy by size criteria or by positron emission tomography (PET)
                       scan

                    -  If the lymph nodes in the contralateral mediastinum and neck are visible by
                       contrast CT scan of the chest AND are ≥ 1.0 cm OR if contralateral
                       involvement is suggested by PET scan, lymph nodes must be confirmed negative
                       by one of the above diagnostic procedures AND N3 status must be confirmed
                       negative by histology or cytology

                    -  No palpable lymph nodes in the supraclavicular areas or higher in the neck
                       unless proven benign by excisional biopsy

                    -  A nodal biopsy or needle aspiration may be omitted provided all of the
                       following criteria are true:

                         -  Paralyzed left true vocal cord by bronchoscopy or indirect laryngoscopy

                         -  Nodes visible in the aortopulmonary window (level 5) region on CT scan

                         -  Distinct primary tumor (separate from the nodes) is visible by CT scan

                         -  No evidence of subcarinal nodal involvement by CT scan NOTE: **PET scan
                            positivity is not sufficient to establish N2 nodal status

          -  Measurable disease by chest x-ray and/or contrast-enhanced CT scan

          -  Candidate for surgery

               -  Resectable disease

          -  No distant metastases, including other ipsilateral or contralateral parenchymal
             lesions or liver or adrenal metastases, by history or physical examination,
             fludeoxyglucose F 18 PET scan, MRI or CT scan of the brain, chest x-ray and/or CT scan
             of the lungs and upper abdomen

        PATIENT CHARACTERISTICS:

        Age

          -  18 and over

        Performance status

          -  Zubrod 0-1

        Life expectancy

          -  Not specified

        Hematopoietic

          -  Absolute neutrophil count ≥ 1,800/mm^3

          -  Platelet count ≥ 100,000/mm^3

          -  Hemoglobin ≥ 10.0 g/dL (transfusion or other intervention allowed)

        Hepatic

          -  ALT and AST ≤ 2.5 times upper limit of normal (ULN)

          -  Alkaline phosphatase ≤ 2.5 times ULN

          -  Bilirubin ≤ 1.5 times ULN

          -  No hepatic insufficiency resulting in clinical jaundice or coagulation defects

        Renal

          -  Creatinine clearance ≥ 60 mL/min

        Cardiovascular

          -  No unstable angina or congestive heart failure requiring hospitalization within the
             past 6 months

          -  No transmural myocardial infarction within the past 6 months

        Pulmonary

          -  FEV_1 ≥ 2.0 L OR

          -  Predicted post-resection FEV_1 ≥ 0.8 L

          -  DLCO ≥ 50% of predicted

          -  No chronic obstructive pulmonary disease exacerbation

          -  No other respiratory illness requiring hospitalization or that would preclude study
             therapy

        Immunologic

          -  No AIDS

          -  No prior allergic reaction to the study drugs

          -  No history of severe hypersensitivity to other drugs formulated with polysorbate 80

          -  No acute bacterial or fungal infection requiring IV antibiotics

        Other

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  No unintentional weight loss > 5% of body weight within the past 6 months

          -  No pre-existing peripheral neuropathy ≥ grade 2

          -  No other invasive malignancy within the past 3 years except nonmelanoma skin cancer or
             carcinoma in situ of the breast, oral cavity, or cervix

          -  No other severe active comorbidity

        PRIOR CONCURRENT THERAPY:

        Biologic therapy

          -  No prior biological agent for this cancer

          -  No concurrent filgrastim (G-CSF), sargramostim (GM-CSF), or pegfilgrastim during study
             induction therapy (for patients randomized to the chemoradiotherapy arm)

        Chemotherapy

          -  No prior systemic chemotherapy for this cancer

               -  Prior chemotherapy for a different cancer allowed

        Endocrine therapy

          -  Not specified

        Radiotherapy

          -  No prior radiotherapy to the region of this cancer that would result in overlap of
             radiotherapy fields

          -  No routine post-operative radiotherapy

          -  No concurrent intensity modulated radiotherapy

        Surgery

          -  See Disease Characteristics

        Other

          -  No prior gefitinib for this cancer

          -  No concurrent amifostine