Issues in nonoperative management of locally advanced non-small-cell lung cancer

The challenge for oncologists treating patients with stage III non-small-cell lung cancer (NSCLC) is to optimize a treatment strategy using nonsurgical therapies. The recognition that chemotherapy response rates for patients with previously untreated locally advanced NSCLC are higher than for those with metastatic tumors led to the testing of induction chemotherapy prior to thoracic radiotherapy. The regimen of induction vinblastine and cisplatin followed by standard thoracic radiotherapy is considered by many to be the optimal regimen against which future nonsurgical approaches should be tested. In a trial conducted by the European Organization for the Research and Treatment of Cancer, a significant survival advantage favored daily low-dose cisplatin/radiotherapy and weekly cisplatin/radiotherapy over radiotherapy alone. Presumably, the simultaneous delivery of low-dose cisplatin with radiotherapy enhanced local tumor response, and the use of higher drug doses in the induction regimens deterred the progression of micrometastatic disease. The principal disadvantage of concomitant therapy is the enhancement of normal tissue toxicity, both hematologic and esophageal, resulting in unnecessary patient morbidity and attenuation of radiotherapy and/or chemotherapy delivery. The current phase III Radiation Treatment Oncology Group trial seeks to determine the risk/benefit ratio of concurrent versus sequential delivery of chemoradiotherapy as well as the additional value of oral etoposide in this multimodality regimen. Accrual will be completed in 1998. There is also increasing interest in interdigitating systemic agents that have been established to be more active in metastatic NSCLC than cisplatin/etoposide with thoracic radiotherapy for stage III disease. Phase I/II trials using agents like carboplatin and paclitaxel with thoracic radiotherapy are summarized, as are plans for phase III testing.