Irinotecan, cisplatin/carboplatin, and COX-2 inhibition in small-cell lung cancer

Recent findings indicate significant prolongation of survival and time to disease progression with irinotecan (CPT-11, Camptosar)/cisplatin vs etoposide/cisplatin in extensive-stage small-cell lung cancer, and a larger-scale phase III trial has been planned to provide more definitive data on the benefits of the irinotecan/cisplatin combination in this setting. Early-phase studies indicate that the activity of carboplatin (Paraplatin) in small-cell lung cancer is comparable to that of cisplatin, and that combining irinotecan on a day 1 and 8 schedule with split-dose carboplatin is feasible. Inhibition of the cyclooxygenase-2 (COX-2) enzyme, which is active in tumorigenesis, may augment efficacy and reduce toxicity of platinum/irinotecan combinations. A phase II trial has been designed to compare irinotecan/carboplatin and irinotecan/cisplatin combinations with or without the COX-2 inhibitor celecoxib (Celebrex) in patients with extensive-stage small-cell lung cancer. Results of these trials will help define the roles of platinum/irinotecan combinations and COX-2 inhibition in treatment for small-cell lung cancer.