Combined-modality therapies for non-small cell lung cancer

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Abstract
Regionally advanced stage III non-small cell lung cancer (NSCLC) accounts for nearly 40% of all presentations of NSCLC. In the past, such patients received radiotherapy alone, but the median and long-term survival durations were disappointingly poor. Past attempts at combining chemotherapy and radiation were also disappointing, and were troubled by low doses of radiation or orthovoltage equipment or both. Recently, cisplatin-containing regimens have shown some efficacy in stage IV disease. The response rate for these combinations in stage III disease is nearly double that in stage IV disease. The greater response in stage III has led to a series of trials of sequenced chemotherapy and radiotherapy for treatment of regionally advanced (un-resectable stage IIIA and IIIB) NSCLC. Several randomized trials have now shown a statistically significant advantage for the combined modality over radiation alone regarding time to treatment failure, median survival duration, and percent of long-term survivors. Other trials have focused on the concurrent use of chemotherapy and radiotherapy. Several pilot studies have suggested that concurrent cisplatin plus chest irradiation can produce apparently beneficial results with respect to local control and are the subject of ongoing clinical trials. At the University of Maryland Cancer Center, we have combined weekly carboplatin 100 mg/m2 with concurrent chest irradiation. The preliminary results are very encouraging. The toxicity of this treatment program is very manageable, and preliminary data suggest excellent local control and survival. Other pilot studies have suggested that combination chemotherapy with concurrent radiotherapy is also technically feasible. Such combined chemotherapy/radiotherapy programs will be the subject of ongoing clinical trials. Current data favor the use of combined chemotherapy and radiotherapy over radiotherapy alone for stage III NSCLC. This approach offers the possibility of improved survival with the combined-modality therapy, and offers even further potential benefit for earlier-stage disease.