© 1999 Kluwer Academic Publishers. Printed in the Netherlands. Review Chemoradiotherapy interactions and lung toxicity

Background: The combination of high-dose radiotherapy with intensive chemotherapy may improve the prognosis of patients with inoperable, locally advanced non-small-cell lung cancer. In the design of suitable clinical protocols, potential interac-tions of drugs and radiation in the tumour, the lung and other critical normal tissues have to be considered. Methods: From experimental data on chemotherapy radio-therapy interactions and based on knowledge about the biology of non-small cell lung cancer and the pathogenesis of radiation pneumopathy, the principles which should be considered in the design of treatment schedules are developed. Results: For the increase in local tumour control, further escalation of radiation dose should be considered first. The most critical issue for lung toxicity may be the volume of the 30 Gy isodose. Yet, the most critical normal tissue which may limit the further increase in dose and dose intensity appears to be the oesophagus. Conclusions: Since the main cause of treatment failure remains local recurrence, further increase in locoregional cyto-toxicity is the first priority in locally advanced non-small-cell lung cancer. This can best be achieved by increasing radiation dose and dose intensity further. Yet, there may also be a role for simultaneous radiochemotherapy, even if this would in-crease the lung volume which develops radiation pneumopathy and thus the severity of symptoms. This problem should be dealt with by reducing the irradiated lung volume by use of conformal treatment planning. The most critical side effects will then be due to increased severity of acute oesophagitis. Key words: drug radiation interactions, lung damage, non-small-cell lung cancer, radiochemotherap