Radiation and simultaneous cisplatin in non-small cell lung cancer

Phase III non-small cell lung cancer trials comparing radiation and simultaneous single agent cisplatin-radiation, as well as, Phase II trials of cisplatin containing combination regimens and concurrent thoracic radiation used as preoperative or as definitive therapy in stage III non-small cell lung cancer are reviewed.

The prognostic significance of the new international staging system with respect to clinical Stage III disease is described and discussed in this review because it has important implications for clinical trials. The results of four randomized Phase III trials and one Phase II trial which evaluated radiation therapy and single agent cisplatin are reviewed. The data from studies of combination chemotherapy and concurrent thoracic radiation observed in two consecutive Rush University Phase II trials and in a randomized Phase II Mayo Clinic trial are described. Eight phase two studies in which thoracic radiation and simultaneous cisplatin containing combination chemotherapy were given as preoperative treatment are compared.

Studies evaluating the prognostic significance of the new staging system (IIIa vs IIIb) have shown conflicting results. In Rush University trials there has been a significant difference for IIIa versus IIIb and in particular the tumors which are invading the mediastinum or chest wall without obvious mediastinal lymph node metastases appear to have the best prognosis. Similarly randomized trials evaluating curative doses of thoracic radiation therapy with or without current single agent cisplatin have shown contradictory results. One of the four randomized trials have shown superior survival with patients treated with radiation and simultaneous daily cisplatin. Toxicity with cisplatin combination chemotherapy regimens and split course radiation has been acceptable. In Phase II non-surgical trials preoperative treatment consisting of cisplatin containing combination regimens given simultaneously with thoracic radiation have shown that this type of combined modality therapy is feasible and that the rates of resectability appear to be higher than would be expected with surgery alone. Survival results from six of these studies appear to be superior to results reported for radiation or surgery alone.

Additional data are needed to determine the prognostic significance of the new staging system for clinical Stage III non-small cell lung cancer patients. Similarly, additional Phase III trials will be required to determine the role of thoracic radiation and concurrent single agent cisplatin, as well as, concurrent cisplatin combination regimens. Treatment with preoperative radiation and concurrent cisplatin containing combination therapies is feasible and relatively safe. Phase III trials are needed to determine the impact of neoadjuvant chemoradiation therapy and surgery in Stage III patients.