Treatment of Locally Advanced Non-Small Cell Lung Cancer with Combination of Chemotherapy and Radiation

ABSTRACT

The treatment of locally advanced non-small cell lung cancer has improved substantially over the past 20 years. Almost three times as many patients are able to achieve long-term survival today compared with the mid-1980s. This improvement has been possible through the cooperation of physicians from different specialties involved in the care of lung cancer patients. More accurate staging, with the use of positron emission tomography, led to more accurate stage classification. Patients with detectable systemic disease can be spared from an aggressive local therapy whereas patients with small volume, stage IIIB, can receive the most appropriate treatment. Clinical trials in the United States and around the world have identifed the role of each treatment modality and the appropriate timing of administration. The present standard of care is the concurrent administration of cisplatin-based chemotherapy and radiotherapy. This is a treatment that can be associated with significant morbidity, and patient selection is paramount. Chronological age, by itself, should not be a reason to deny a patient the most appropriate treatment for lung cancer. The presence of comorbidities, on the other hand, is a key factor in deciding the most appropriate treatment. When the concurrent administration of chemo- and radiotherapy is not appropriate, the sequential delivery of these two modalities is superior to each of them given alone. Over the last 6 months, two trials have shown that erlotinib (an epidermal growth factor receptor inhibitor) and bevacizumab (a vascular endothelial growth factor inhibitor) improve survival in non-small cell lung cancer patients. These findings represent a landmark in the care of lung cancer patients. We are entering an era of improved patient identification and more logical therapeutic approaches. The incorporation of these “targeted therapies” in the treatment of patients with locally advanced disease is being actively investigated and will, it is hoped, translate into significant therapeutic benefits for the patients.

Non-small cell lung cancer - chemotherapy - radiotherapy - stage IIIB

REFERENCES

• 1 Schild S E, Stella P J, Geyer S M et al.. A phase III trial comparing chemotherapy plus either once a day radiotherapy (QD RT) or twice a day radiotherapy (BID RT) in stage III non-small cell lung cancer.  Int J Radiat Oncol Biol Physiol. 2002;  54 370-378
• 2 Schild S E, Stella P J, Geyer S M et al.. The outcome of combined-modality therapy for stage III non-small cell lung cancer in the elderly.  J Clin Oncol. 2003;  21 3201-3206
• 3 Dillman R O, Seagren S L, Propert K J et al.. A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III non-small cell lung cancer.  N Engl J Med. 1990;  323 940-945
• 4 Schaake-Koning C, Dalesio O, Festen J et al.. Effects of concomitant cisplatin and radiotherapy on inoperable non-small cell lung cancer.  N Engl J Med. 1992;  326 524-530
• 5 Clamon G, Herndon J, Cooper R, Chang A Y, Rosenman J, Green M R. Radiosensitization with carboplatin for patients with unresectable stage III non-small cell lung cancer: a phase III trial of the Cancer and Leukemia Group B and the Eastern Cooperative Oncology Group.  J Clin Oncol. 1999;  17 4-11
• 6 Furuse K, Fukuoka M, Kawahara M et al.. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non-small cell lung cancer.  J Clin Oncol. 1999;  17 2692-2699
• 7 Albain K S, Rush V W, Crowley J J 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. 1995;  13 1880-1892
• 8 Albain K S, Crowley J J, Gandara D R et al.. Concurrent cisplatin, etoposide, and chest radiotherapy in pathological stage IIIB non-small cell lung cancer: a Southwest Oncology Group Phase II Study, SWOG 9019.  J Clin Oncol. 2002;  20 3454-3460
• 9 Gandara D R, Chansky K, Albain K S et al.. Consolidation docetaxel after concurrent chemoradiotherapy in stage IIIB non-small cell lung cancer: phase II Southwest Oncology Group Study S9504.  J Clin Oncol. 2003;  21 2004-2010
• 10 Vokes E E, Miller A A, Green M R et al.. Randomized phase II study of cisplatin with gemcitabine or paclitaxel or vinorelbine as induction chemotherapy followed by concomitant chemoradiotherapy for stage IIIB non-small cell lung cancer: Cancer and Leukemia Group B study 9431.  J Clin Oncol. 2002;  20 4191-4198
• 11 Curran W J, Scott C B, Langer C J et al.. Long-term benefit is observed in a phase III comparison of sequential vs concurrent chemo-radiation for patients with unresected stage III NSCLC: RTOG 9410 [abstract 2499].  Proc Am Soc Clin Oncol. 2003;  22 621
• 12 Vokes E E, Herndon J E, Kelley M J, Watson D, Cicchetti M G, Green M R. Induction chemotherapy followed by concomitant chemoradiotherapy versus CT/XRT alone for regionally advaned unresectable non-small cell lung cancer: intial analysis of a randomized phase III trial [abstract 7005].  J Clin Oncol. 2004;  22 7005
• 13 Kubota K, Furuse K, Kawahara M et al.. Role of radiotherapy in combined modality treatment of locally advanced non-small cell lung cancer.  J Clin Oncol. 1994;  12 1547-1552
• 14 Saunders M, Dische S, Barrett A, Harvey A, Griffiths G, Parmar M. Continuous, hyperfractionated, accelerated radiotherapy (CHART) versus conventional radiotherapy in non-small cell lung cancer: mature data from the randomized multicenter trial.  Radiother Oncol. 1999;  52 137-148
• 15 Rusch V W, Giroux D J, Kraut M J et al.. Induction chemoradiation and surgical resection for non-small cell lung carcinomas of the superior sulcus: initial results of Southwest Oncology Group trial 9416 (Intergroup trial 0160).  J Thorac Cardiovasc Surg. 2001;  121 472-483