Stage IV NSCLC Treatment
Radiation therapy may be effective in palliating symptomatic patients with local involvement of NSCLC with any of the following:
- Tracheal, esophageal, or bronchial compression.
- Vocal cord paralysis.
- Superior vena cava syndrome.
In some cases, endobronchial laser therapy and/or brachytherapy have been used to alleviate proximal obstructing lesions.
Although EBRT is frequently prescribed for symptom palliation, there is no consensus on which fractionation scheme should be used. Although different multifraction regimens appear to provide similar symptom relief,[42,43,44,45,46,47] single-fraction radiation may be insufficient for symptom relief compared with hypofractionated or standard regimens, as evidenced in the NCT00003685 trial.[Level of evidence: 1iiC] Evidence of a modest increase in survival in patients with a better PS given high-dose radiation therapy is available.[3,48][Level of evidence: 1iiA] In closely observed asymptomatic patients, treatment may often be appropriately deferred until symptoms or signs of a progressive tumor develop.
- A systematic review identified six randomized trials of high-dose rate brachytherapy (HDREB) alone or with EBRT or laser therapy.
- Better overall symptom palliation and fewer retreatments were required in previously untreated patients using EBRT alone.[Level of evidence: 1iiC]
- HDREB provided palliation of symptomatic patients with recurrent endobronchial obstruction previously treated by EBRT, when it was technically feasible.
Treatment Options Under Clinical Evaluation
Treatment options under clinical evaluation for stage IV NSCLC include the following:
- New chemotherapy regimens.
- Other systemic agents.
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IV non-small cell lung cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
- Bezjak A, Dixon P, Brundage M, et al.: Randomized phase III trial of single versus fractionated thoracic radiation in the palliation of patients with lung cancer (NCIC CTG SC.15). Int J Radiat Oncol Biol Phys 54 (3): 719-28, 2002.
- Macbeth F, Toy E, Coles B, et al.: Palliative radiotherapy regimens for non-small cell lung cancer. Cochrane Database Syst Rev (3): CD002143, 2001.
- Sundstr�m S, Bremnes R, Aaseb� U, et al.: Hypofractionated palliative radiotherapy (17 Gy per two fractions) in advanced non-small-cell lung carcinoma is comparable to standard fractionation for symptom control and survival: a national phase III trial. J Clin Oncol 22 (5): 801-10, 2004.
- Miller JI Jr, Phillips TW: Neodymium:YAG laser and brachytherapy in the management of inoperable bronchogenic carcinoma. Ann Thorac Surg 50 (2): 190-5; discussion 195-6, 1990.
- Weick JK, Crowley J, Natale RB, et al.: A randomized trial of five cisplatin-containing treatments in patients with metastatic non-small-cell lung cancer: a Southwest Oncology Group study. J Clin Oncol 9 (7): 1157-62, 1991.
- Delbaldo C, Michiels S, Rolland E, et al.: Second or third additional chemotherapy drug for non-small cell lung cancer in patients with advanced disease. Cochrane Database Syst Rev (4): CD004569, 2007.
- Ardizzoni A, Boni L, Tiseo M, et al.: Cisplatin- versus carboplatin-based chemotherapy in first-line treatment of advanced non-small-cell lung cancer: an individual patient data meta-analysis. J Natl Cancer Inst 99 (11): 847-57, 2007.
- Jiang J, Liang X, Zhou X, et al.: A meta-analysis of randomized controlled trials comparing carboplatin-based to cisplatin-based chemotherapy in advanced non-small cell lung cancer. Lung Cancer 57 (3): 348-58, 2007.
- Hotta K, Matsuo K, Ueoka H, et al.: Meta-analysis of randomized clinical trials comparing Cisplatin to Carboplatin in patients with advanced non-small-cell lung cancer. J Clin Oncol 22 (19): 3852-9, 2004.
- D'Addario G, Pintilie M, Leighl NB, et al.: Platinum-based versus non-platinum-based chemotherapy in advanced non-small-cell lung cancer: a meta-analysis of the published literature. J Clin Oncol 23 (13): 2926-36, 2005.
- Rajeswaran A, Trojan A, Burnand B, et al.: Efficacy and side effects of cisplatin- and carboplatin-based doublet chemotherapeutic regimens versus non-platinum-based doublet chemotherapeutic regimens as first line treatment of metastatic non-small cell lung carcinoma: a systematic review of randomized controlled trials. Lung Cancer 59 (1): 1-11, 2008.
- Pujol JL, Barlesi F, Daur�s JP: Should chemotherapy combinations for advanced non-small cell lung cancer be platinum-based? A meta-analysis of phase III randomized trials. Lung Cancer 51 (3): 335-45, 2006.
- Douillard JY, Laporte S, Fossella F, et al.: Comparison of docetaxel- and vinca alkaloid-based chemotherapy in the first-line treatment of advanced non-small cell lung cancer: a meta-analysis of seven randomized clinical trials. J Thorac Oncol 2 (10): 939-46, 2007.
- Belani CP, Ramalingam S, Perry MC, et al.: Randomized, phase III study of weekly paclitaxel in combination with carboplatin versus standard every-3-weeks administration of carboplatin and paclitaxel for patients with previously untreated advanced non-small-cell lung cancer. J Clin Oncol 26 (3): 468-73, 2008.
- Schuette W, Blankenburg T, Guschall W, et al.: Multicenter randomized trial for stage IIIB/IV non-small-cell lung cancer using every-3-week versus weekly paclitaxel/carboplatin. Clin Lung Cancer 7 (5): 338-43, 2006.
- Scagliotti GV, Parikh P, von Pawel J, et al.: Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol 26 (21): 3543-51, 2008.
- Langer CJ, Vangel M, Schiller J, et al.: Age-specific subanalysis of ECOG 1594: fit elderly patients (70-80 YRS) with NSCLC do as well as younger pts (<70). [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-2571, 2003.
- Langer CJ, Manola J, Bernardo P, et al.: Cisplatin-based therapy for elderly patients with advanced non-small-cell lung cancer: implications of Eastern Cooperative Oncology Group 5592, a randomized trial. J Natl Cancer Inst 94 (3): 173-81, 2002.
- Ries LA: Influence of extent of disease, histology, and demographic factors on lung cancer survival in the SEER population-based data. Semin Surg Oncol 10 (1): 21-30, 1994 Jan-Feb.
- Ramsey SD, Howlader N, Etzioni RD, et al.: Chemotherapy use, outcomes, and costs for older persons with advanced non-small-cell lung cancer: evidence from surveillance, epidemiology and end results-Medicare. J Clin Oncol 22 (24): 4971-8, 2004.
- Effects of vinorelbine on quality of life and survival of elderly patients with advanced non-small-cell lung cancer. The Elderly Lung Cancer Vinorelbine Italian Study Group. J Natl Cancer Inst 91 (1): 66-72, 1999.
- Takeda K, Kudoh S, Nakagawa K, et al.: Randomized phase III study of docetaxel (D) versus vinorelbine (V) for elderly patients (pts) with advanced non-small cell lung cancer (NSCLC): Results of a West Japan Thoracic Oncology Group trial (WJTOG9904). [Abstract] J Clin Oncol 23 (Suppl 16): A-7009, 2005.
- Schiller JH, Harrington D, Belani CP, et al.: Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 346 (2): 92-8, 2002.
- Belani CP, Fossella F: Elderly subgroup analysis of a randomized phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for first-line treatment of advanced nonsmall cell lung carcinoma (TAX 326). Cancer 104 (12): 2766-74, 2005.
- Lilenbaum RC, Herndon JE 2nd, List MA, et al.: Single-agent versus combination chemotherapy in advanced non-small-cell lung cancer: the cancer and leukemia group B (study 9730). J Clin Oncol 23 (1): 190-6, 2005.
- Hensing TA, Peterman AH, Schell MJ, et al.: The impact of age on toxicity, response rate, quality of life, and survival in patients with advanced, Stage IIIB or IV nonsmall cell lung carcinoma treated with carboplatin and paclitaxel. Cancer 98 (4): 779-88, 2003.
- Sweeney CJ, Zhu J, Sandler AB, et al.: Outcome of patients with a performance status of 2 in Eastern Cooperative Oncology Group Study E1594: a Phase II trial in patients with metastatic nonsmall cell lung carcinoma . Cancer 92 (10): 2639-47, 2001.
- Tester WJ, Stephenson P, Langer CJ, et al.: ECOG 1599: randomized phase II study of paclitaxel/carboplatin or gemcitabine/cisplatin in performance status (PS) 2 patients with advanced non-small cell lung cancer (NSCLC). [Abstract] J Clin Oncol 22 (Suppl 14): A-7055, 630s, 2004.
- Vansteenkiste JF, Vandebroek JE, Nackaerts KL, et al.: Clinical-benefit response in advanced non-small-cell lung cancer: A multicentre prospective randomised phase III study of single agent gemcitabine versus cisplatin-vindesine. Ann Oncol 12 (9): 1221-30, 2001.
- Hickish TF, Smith IE, O'Brien ME, et al.: Clinical benefit from palliative chemotherapy in non-small-cell lung cancer extends to the elderly and those with poor prognostic factors. Br J Cancer 78 (1): 28-33, 1998.
- Sandler A, Gray R, Perry MC, et al.: Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355 (24): 2542-50, 2006.
- Reck M, von Pawel J, Zatloukal P, et al.: Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. J Clin Oncol 27 (8): 1227-34, 2009.
- Lynch TJ, Patel T, Dreisbach L, et al.: Cetuximab and first-line taxane/carboplatin chemotherapy in advanced non-small-cell lung cancer: results of the randomized multicenter phase III trial BMS099. J Clin Oncol 28 (6): 911-7, 2010.
- Pirker R, Pereira JR, Szczesna A, et al.: Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet 373 (9674): 1525-31, 2009.
- Khambata-Ford S, Harbison CT, Hart LL, et al.: Analysis of potential predictive markers of cetuximab benefit in BMS099, a phase III study of cetuximab and first-line taxane/carboplatin in advanced non-small-cell lung cancer. J Clin Oncol 28 (6): 918-27, 2010.
- Mok TS, Wu YL, Thongprasert S, et al.: Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 361 (10): 947-57, 2009.
- Brodowicz T, Krzakowski M, Zwitter M, et al.: Cisplatin and gemcitabine first-line chemotherapy followed by maintenance gemcitabine or best supportive care in advanced non-small cell lung cancer: a phase III trial. Lung Cancer 52 (2): 155-63, 2006.
- Park JO, Kim SW, Ahn JS, et al.: Phase III trial of two versus four additional cycles in patients who are nonprogressive after two cycles of platinum-based chemotherapy in non small-cell lung cancer. J Clin Oncol 25 (33): 5233-9, 2007.
- Socinski MA, Schell MJ, Peterman A, et al.: Phase III trial comparing a defined duration of therapy versus continuous therapy followed by second-line therapy in advanced-stage IIIB/IV non-small-cell lung cancer. J Clin Oncol 20 (5): 1335-43, 2002.
- von Plessen C, Bergman B, Andresen O, et al.: Palliative chemotherapy beyond three courses conveys no survival or consistent quality-of-life benefits in advanced non-small-cell lung cancer. Br J Cancer 95 (8): 966-73, 2006.
- Ciuleanu T, Brodowicz T, Zielinski C, et al.: Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study. Lancet 374 (9699): 1432-40, 2009.
- Danson S, Middleton MR, O'Byrne KJ, et al.: Phase III trial of gemcitabine and carboplatin versus mitomycin, ifosfamide, and cisplatin or mitomycin, vinblastine, and cisplatin in patients with advanced nonsmall cell lung carcinoma. Cancer 98 (3): 542-53, 2003.
- Pfister DG, Johnson DH, Azzoli CG, et al.: American Society of Clinical Oncology treatment of unresectable non-small-cell lung cancer guideline: update 2003. J Clin Oncol 22 (2): 330-53, 2004.
- Smit EF, van Meerbeeck JP, Lianes P, et al.: Three-arm randomized study of two cisplatin-based regimens and paclitaxel plus gemcitabine in advanced non-small-cell lung cancer: a phase III trial of the European Organization for Research and Treatment of Cancer Lung Cancer Group--EORTC 08975. J Clin Oncol 21 (21): 3909-17, 2003.
- Kubota K, Watanabe K, Kunitoh H, et al.: Phase III randomized trial of docetaxel plus cisplatin versus vindesine plus cisplatin in patients with stage IV non-small-cell lung cancer: the Japanese Taxotere Lung Cancer Study Group. J Clin Oncol 22 (2): 254-61, 2004.
- Georgoulias V, Ardavanis A, Agelidou A, et al.: Docetaxel versus docetaxel plus cisplatin as front-line treatment of patients with advanced non-small-cell lung cancer: a randomized, multicenter phase III trial. J Clin Oncol 22 (13): 2602-9, 2004.
- Sandler AB, Nemunaitis J, Denham C, et al.: Phase III trial of gemcitabine plus cisplatin versus cisplatin alone in patients with locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol 18 (1): 122-30, 2000.
- Lester JF, Macbeth FR, Toy E, et al.: Palliative radiotherapy regimens for non-small cell lung cancer. Cochrane Database Syst Rev (4): CD002143, 2006.
- Ung YC, Yu E, Falkson C, et al.: The role of high-dose-rate brachytherapy in the palliation of symptoms in patients with non-small-cell lung cancer: a systematic review. Brachytherapy 5 (3): 189-202, 2006 Jul-Sep.