|
||||||||||||||||||||||
|
|
Phase II Pilot Study of Neoadjuvant Chemotherapy with CDDP/VP-16 plus Concurrent Chest and Optional Brain Irradiation in Patients with Stage III non-Small Cell Lung Carcinoma (Summary Last Modified 11/90)
Basic Trial Information
Objectives I. Determine the feasibility and toxicity of treating patients with Stage III non-small cell lung cancer with cisplatin/etoposide for two cycles, concurrent with a program of continuous, fractionated chest and optional whole-brain irradiation, followed by surgical resection. II. Assess the objective response rate, resectability rate, and proportion of patients free of microscopic residual disease after such an approach. III. Assess whether immunocytochemical analysis and/or DNA analysis (ploidy, proliferative fraction) define subset(s) of patients who benefit from this combined modality approach, and potentially assess the impact of chemoradiotherapy on the ploidy of the tumor. Entry Criteria Disease Characteristics: See General Eligibility Criteria Patient Characteristics: See General Eligibility Criteria General Eligibility Criteria: Patients at least 18 years of age with regionally advanced non-small cell lung cancer (squamous, adeno-, and large cell carcinoma); this includes Stage IIIb and selected Stage IIIa (T1-3N2) tumors. Eligibility for this study may be established by any one or more of the following: positive N2 lymph nodes; positive N3 lymph nodes (those with positive supraclavicular lymph nodes must not have disease extending into the cervical region and must have no evidence of metastatic disease according to the criteria described below); lesions demonstrated to be T4 by virtue of documented recurrent laryngeal nerve involvement, direct extension into the trachea at bronchoscopy, or direct extension into the mediastinum at mediastinoscopy or exploratory thoracotomy (written documentation of direct extension must be provided in the operative report); or T3 lesions by virtue of superior sulcus or direct chest wall involvement, but only if N2 or N3 disease is found by mediastinoscopy. Mediastinal adenopathy or direct mediastinal invasion by the primary must be confirmed by mediastinoscopy or exploratory thoracotomy and not by CT scan findings alone, and there must be histologic proof of non-small cell lung cancer; the only exceptions to these criteria are the case of a T4 lesion as above, for which a cytology specimen from the primary is acceptable, or the case of a patient already having histologic proof of non-small cell lung cancer, for whom cytologic proof of N2 or N3 involvement by fine needle or Wang needle aspiration is acceptable. There must be no evidence of metastatic disease after performance of the following tests: history and physical examination; WBC including differential and platelet count; chemistry battery including alkaline phosphatase, SGOT or SGPT, bilirubin, albumin, and calcium; chest x-ray; CT of brain with contrast or MRI scan of brain; CT of upper abdomen and chest to exclude metastatic disease involving the liver, adrenals, or contralateral chest (biopsy or aspiration cytology is strongly recommended to confirm the diagnosis of CT abnormalities that may represent metastatic disease); and bone scan (abnormalities on bone scan should be further evaluated by appropriate plain radiographs or by aspiration cytology or both in order to rule out metastatic disease; a bone scan abnormality with normal radiograph is considered metastatic disease unless biopsied or otherwise clinically explained). Patients with small cell lung cancer, bronchoalveolar carcinoma with lobar or multilobar involvement, T4 disease by virtue of pleural seeding or pleural effusion, or superior vena caval syndrome are not eligible. Patients must not have received any prior chemotherapy or radiotherapy and must be considered medically to be a candidate for surgery as determined by the attending thoracic surgeon. Measurable or evaluable tumor by chest x-ray or CT scan is required, as is a SWOG performance status of 2 or better and a life expectancy of at least 8 weeks. Patients must have WBC of at least 4,000, platelets at least 100,000, and serum creatinine no more than 1.6 mg/dl or creatinine clearance at least 50 ml/minute; unless there is benign liver disease, serum bilirubin and SGOT must be no greater than 1.2 times institutional normal and alkaline phosphatase must be no greater than 1.5 times institutional normal. If the preregistration FEV1 is not greater than 2.0 liters, the predicted postresection FEV1 must be over 800 cc based on quantitative lung V/Q scan. Prior malignant disease other than inactive cervical carcinoma in situ or inactive nonmelanomatous skin cancer or other cancer if patient has been disease free for at least 5 years excludes, as does the presence of any other medical illnesses that cannot be adequately controlled with appropriate medication (e.g., myocardial infarction within the previous 3 months and refractory congestive heart failure). Expected Enrollment 100 patients will be accrued over an estimated 2 years. Outline Nonrandomized study. All patients are treated on Regimen A; those with stable or responding disease then undergo surgery on Regimen B. Patients with residual disease following surgery are treated on Regimen C. Regimen A: 2-Drug Combination Chemotherapy plus Radiotherapy. Cisplatin, CDDP, NSC-119875; Etoposide, VP-16, NSC-141540; plus chest irradiation using supervoltage equipment of 4 MeV or greater (Co60 is not allowed, and electrons may be used only for supraclavicular treatment) and optional prophylactic cranial irradiation. Regimen B: Surgery. Tumor resection. Regimen C: Radiotherapy plus 2-Drug Combination Chemotherapy. Tumor boost irradiation; plus CDDP; VP-16.Published Results Albain K, Rusch V, Crowley J, et al.: Long-term survival after concurrent cisplatin/etoposide (PE) plus chest radiotherapy (RT) followed by surgery in bulky, stages IIIA(N2) and IIIB non-small cell lung cancer (NSCLC): six-year outcomes from Southwest Oncology Group Study 8805. [Abstract] Proceedings of the American Society of Clinical Oncology 18: A1801, 467a, 1999. Albain KS, Rusch VW, Crowley JJ, et al.: Concurrent cisplatin/etoposide plus chest radiotherapy followed by surgery for stages IIIA (N2) and IIIB non-small-cell lung cancer: mature results of Southwest Oncology Group phase II study 8805. J Clin Oncol 13 (8): 1880-92, 1995.[PUBMED Abstract] Albain K, Rusch V, Crowley J, et al.: Concurrent cisplatin/etoposide (PE) + chest radiation (CRT) followed by surgery for stages 3A(N2) and 3B non-small cell lung cancer: completed analysis of SWOG-8805. [Abstract] Proceedings of the American Society of Clinical Oncology 13: A-1120, 337, 1994. Rusch VW, Albain KS, Crowley JJ, et al.: Neoadjuvant therapy: a novel and effective treatment for stage IIIb non-small cell lung cancer. Southwest Oncology Group. Ann Thorac Surg 58 (2): 290-4; discussion 294-5, 1994.[PUBMED Abstract] Rusch VW, Albain KS, Crowley JJ, et al.: Surgical resection of stage IIIA and stage IIIB non-small-cell lung cancer after concurrent induction chemoradiotherapy. A Southwest Oncology Group trial. J Thorac Cardiovasc Surg 105 (1): 97-104; discussion 104-6, 1993.[PUBMED Abstract] Trial Lead Organizations Southwest Oncology Group
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. |
NCI Home |
Images Version |
Contact Us |
Policies |
Accessibility |
Viewing Files |
FOIA |
Site Help |
Site Map
|
A Service of the National Cancer Institute |