Neoadjuvant (induction) treatment for non-small cell lung cancer

Abstract

Preoperative treatment for non-small cell lung cancer is not new. but recently it has gained increasing acceptance in the management of locally advanced disease. Preoperative radiotherapy has been studied extensively but has never been demonstrated to improve survival in locally advanced (N2,T3) disease. However, it is still considered part of the accepted management for superior sulcus tumors. In the past 15 years, many Phase II trials have investigated the use of induction chemotherapy or chemoradiotherapy as part of the treatment plan for Stage IIIA patients, especially those with preoperatively identified N2 disease who have a poor prognosis following primary surgical resection, with or without postoperative adjuvant therapy. Preoperative chemotherapy trials, as exemplified by the Memorial Sloan-Kettering Cancer Center and Toronto MVP (mitomycin, vinblastine, and cisplatin) trials, have demonstrated what appear to be improved median survival time and prolonged 5-year survival when compared to historical controls. More recently, three relatively small randomized trials have demonstrated statistically significant improvement in patients treated preoperatively with induction chemotherapy. More widely investigated in Phase II trials has been the use of chemoradiotherapy as an induction protocol. The chemotherapy has usually been platinum based and has been given prior to, or concurrent with, radiotherapy. The two largest series to date (Rush-Presbyterian and Southwest Oncology Group) have both suggested improved median survival times and prolonged survival using this approach. Three recently completed nonsurgical trials have demonstrated the superiority in median and long-term survival of primary chemoradiotherapy compared to primary radiotherapy alone in treating locally advanced, inoperable Stage IIIA and IIIB lung cancer. Both induction therapy approaches followed by surgical resection are now being tested against nonsurgical approaches in large-scale Phase III trials of clinically Stage IIIA lung cancer patients. A Canadian trial tests induction chemotherapy plus surgery versus radiotherapy alone, and an American in-tergroup trial tests induction chemoradiotherapy plus surgery versus chemoradiotherapy alone. Recently, because of apparent improved survival with induction therapy, interest has been sparked in this approach for more advanced IIIB disease (T4 and N3) and poor-prognosis lesser disease (T2N0 and N1). These encouraging data suggest that induction therapy will play an increasing role in the management of locally advanced lung cancer, whether the local control treatment is surgery or radiotherapy. Ultimately, Phase III trials, now under way, will allow us to determine the best method of primary control.