Neoadjuvant chemotherapy in stage IIIa non-small cell lung cancer.

Background. The efficacy of surgery for patients with non-small cell lung cancer is limited, although recent studies suggest that preoperative chemotherapy may improve survival. We conducted a randomized trial to examine the possible benefit of preoperative chemotherapy and surgery for the treatment of patients with non-small cell lung cancer. Methods. We studied 60 patients (59 men and 1 woman) with stage IIIA non-small cell lung cancer. The patients were randomly assigned to receive either surgery alone or three courses of chemotherapy (6mg of mitomycin per square meter of bodysurface area, 3 g of ifosfamide per square meter, and 50mg of cisplatin per square meter) given intravenously at three-week intervals and followed bysurgery. Allpatients received mediastinal radiation after surgery. The resected tumors were evaluated by means of K-ras oncogene analysis and flow cytometry. Results. The median period o.f survival was 26 months in the patients treated with chemotherapy plus surgery, as compared with 8 months in the patients treated with surgery alone (P<0.001); the median period of disease-free survival 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 treated with chemotherapy plus surgery and 74 percent in the group treated 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 consisted of diploid cells, whereas the patients treated with surgery alone had tumors with aneuploid cells. Conclusions. Preoperative chemotherapy increases the median survival in patients with non-small cell lung cancer. (N Engl J Med 1994;330:153-8)