A RANDOMIZED TRIAL COMPARING PREOPERATIVE CHEMOTHERAPY PLUS SURGERY WITH SURGERY ALONE IN PATIENTS WITH NON-SMALL-CELL LUNG-CANCER

Background. The efficacy of surgery for patients with non-small-cell l ung cancer is limited, although recent studies suggest that preoperati ve chemotherapy may improve survival. We conducted a randomized trial to examine the possible benefit of preoperative chemotherapy and surge ry for the treatment of patients with non-small-cell lung cancer. Meth ods. We studied 60 patients (59 men and 1 woman) with stage IIIA non-s mall-cell lung cancer. The patients were randomly assigned to receive either surgery alone or three courses of chemotherapy (6 mg of mitomyc in per square meter of body-surface area, 3 g of ifosfamide per square meter, and 50 mg of cisplatin per square meter) given intravenously a t three-week intervals and followed by surgery. All patients received mediastinal radiation after surgery. The resected tumors were evaluate d by means of K-ras oncogene analysis and flow cytometry. Results. The median period of survival was 26 months in the patients with chemothe rapy plus surgery, as compared with 8 months in the patients treated w ith surgery alone (P<0.001); the median period of disease-free surviva l was 20 months in the former group, as compared with 5 months in the latter (P<0.001). The rate of recurrence was 56 percent in the group t reated with chemotherapy plus surgery and 74 percent in the group trea ted with surgery alone. The prevalence of mutated K-ras oncogenes was 15 percent among the patients receiving preoperative chemotherapy and 42 percent among those treated with surgery alone (P = 0.05). Most of the patients treated with chemotherapy plus surgery had tumors that co nsisted of diploid cells, whereas the patients treated with surgery al one had tumors with aneuploid cells. Conclusions. Preoperative chemoth erapy increases the median survival in patients with non-small-cell lu ng cancer.