Induction therapy for early-stage non-small-cell lung cancer

Data from adjuvant trials clearly indicate that one of the most important problems in patients with resected non-small-cell lung cancer (NSCLC) is compliance to chemotherapy. In the postoperative setting, significant comorbidities and incomplete recovery after surgery often make it difficult for patients to tolerate or comply with systemic therapy. Therefore, it may be preferable to deliver chemotherapy before surgery as "neoadjuvant" or "induction" chemotherapy. The rationale for using induction chemotherapy is based on evidence that chemotherapy might reduce tumor burden and possess activity against micrometastases, resulting in improved results by surgery, radiotherapy, or a combination. Moreover, induction therapy facilitates in vivo assessment of tumor response or resistance. Potential drawbacks include the risk of perioperative complications, and the possibility that the tumor mass may become unresectable due to disease progression. During the past decade, four phase III randomized trials evaluated the role of induction chemotherapy in stage IIIA NSCLC. The first three studies consistently showed that induction chemotherapy improves survival compared with surgery alone. More recently, a large phase III trial performed by French investigators suggested a survival benefit in stage I/II patients, but not stage IIIA. The high activity of new platinum-based chemotherapy--based on response rate and 1-year survival in advanced disease--reinforces the rationale for the use of these new combinations in early-stage NSCLC, especially for a subset of patients traditionally treated with surgery alone. Several phase III trials are currently evaluating the role of new doublets as induction chemotherapy; these are discussed in the article. The results of these ongoing phase III trials should help clarify the role of induction chemotherapy in early-stage disease.