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.
Natale
Ronald B
RB
Cedars-Sinai Comprehensive Cancer Center, National Lung Cancer Research Program, Salick Health Care, Inc., 8700 Beverly Blvd, Suite C2000, Los Angeles, CA 90048-1804, USA. rnatale@csccc.salick.com
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018288:Carcinoma, Small Cell / Q000188:drug therapy*; D000068579:Celecoxib; D002945:Cisplatin / Q000008:administration & dosage; D002986:Clinical Trials as Topic; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage; D004334:Drug Administration Schedule; D006801:Humans; D000077146:Irinotecan; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008175:Lung Neoplasms / Q000188:drug therapy*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles; D013449:Sulfonamides / Q000008:administration & dosage; D016019:Survival Analysis; D016896:Treatment Outcome
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D000077146:Irinotecan; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib; D002945:Cisplatin; D002166:Camptothecin