Treatment of locally advanced non-small cell lung cancer

Abstract

In this review the following topics are discussed: the complexities of clinical staging in locally advanced non-small cell lung cancer, the results of Phase III non-surgical combined modality studies, the results of Phase II neoadjuvant surgical trials. Although there have been conflicting results, most studies comparing survival of patients with clinical Stages IIIA and IIIB lung cancer have shown significant survival differences between these stage groups. It also appears that patients whose clinical stage is T3, N0 may have the best prognosis and may be the group most likely to benefit from combined-modality treatment. Additional staging data based on findings at mediastinoscopy are needed to confirm this initial observation. Sequential treatment with cisplatin-containing combination chemotherapy followed by radiation appears to produce a modest increase in 2-year survival rates. Further information regarding the effectiveness of this treatment sequence will be provided by a large, ongoing randomized trial comparing radiation alone versus two courses of vinblastine/cisplatin, followed by thoracic irradiation. In a recently reported study thoracic irradiation and concurrent daily cisplatin have produced significantly better survival than radiation alone or radiation combined with weekly cisplatin. Phase III trials of radiation and concurrent combination chemotherapy — particularly etoposide and platinum — should also be done. Both mitomycin/vinblastine/cisplatin and etoposide/cisplatin given with concurrent thoracic irradiation have produced relatively high response rates and encouraging survival results when given prior to pulmonary resection in patients with Stage IIIA non-small cell lung cancer. However, concern about toxicity has resulted in the deletion of mitomycin from an ongoing Phase III trial testing preoperative chemotherapy. In contrast, Phase II trials of preoperative etoposide/cisplatin plus radiation have produced relatively high response rates with acceptable toxicity. These observations have led the Southwest Oncology Group to propose the development of a Phase III trial testing this regimen as preoperative treatment.