Long-term results of neoadjuvant ifosfamide, cisplatin, and etoposide combination in locally advanced non-small-cell lung cancer.

Thirty-three patients with T3,N2,M0 or T4,N2,M0, non-small-cell lung cancer (NSCLC) took part in a phase 2 study in an attempt to evaluate the feasability of neoadjuvant chemotherapy followed by surgery and thoracic radiotherapy. Chemotherapy consisted of daily administration of the following treatment: etoposide, 100 mg/m2; cisplatin, 25 mg/m2; ifosfamide, 1.5 g/m2; and mesna, 1.8 g/m2 for 4 days. Three cycles were planned starting every 21 days. Responding patients underwent a thoracotomy in order to attempt a resection and then received a 45 Gy of thoracic radiotherapy. The results of response and resection rates have been published and the present final report deals with the long-term results. Chemotherapy induced a 55 percent partial response rate and a 15 percent complete response rate allowing a complete resection in 55 percent of the patients. Complete remission was histologically confirmed for the five complete responders. Although the median survival was short (10 months), six patients were long-term survivors (3-year survival rate: 19 percent). Survival was significantly influenced by the type of resection: patients for whom a complete resection was possible survived the longest with a median survival three times that of the other patients. Modalities of relapses differed according to the results of surgery: 8 of the 15 patients who did not undergo a complete surgical resection experienced a local relapse during the first 18 months of follow-up whereas in the complete resection group, central nervous system metastasis was the main site of relapse. We conclude that the neoadjuvants ifosfamide, cisplatin, and etoposide in patients with locally advanced NSCLC are feasible to use and allow a 19 percent 3-year survival rate. These results are the rationale of an ongoing randomized study comparing neoadjuvant chemotherapy followed by surgery and surgery alone. This study is designed to test whether neoadjuvant chemotherapy improves survival of patients with locally advanced NSCLC.