Gemcitabine/cisplatin as induction therapy for stage IIIA N2 non-small-cell lung cancer

Because the majority of patients with stage IIIA N2 non-small-cell lung cancer (NSCLC) ultimately die of distant metastases, recent efforts to improve their intermediate- and long-term survival have focused on neoadjuvant chemotherapy (with or without radiotherapy) as an induction regimen followed by surgical resection. Over the last 15 years, more than 25 phase II trials and two small randomized phase III trials were terminated early because interim analyses confirmed the feasibility of the neoadjuvant approach and suggested a twofold increase in overall survival time compared to surgery alone. The gemcitabine (Gemzar)/cisplatin (Platinol) regimen proved effective in unresectable locally advanced and metastatic NSCLC. Consequently, it is logical to investigate the activity of this combination in locally advanced NSCLC. Preliminary results of five phase II trials have reported an average response rate > 60% in a mixed study population (IIIA and IIIB). Treatment is well tolerated. In studies using the 4-week schedule, the gemcitabine dose was frequently omitted on day 15, mainly due to thrombocytopenia. In January 2000, a randomized clinical trial (Chemotherapy for Early Stages Trial [ChEST]) was initiated in Italy to compare the efficacy of surgery alone vs surgery plus preoperative gemcitabine/cisplatin in early-stage disease (T2-3 N0, T1-2 N1, T3 N1) with the primary end point being progression-free survival.