The emerging world role of irinotecan in lung cancer.
Irinotecan (CPT-11, Camptosar), either alone or in combination with cisplatin (Platinol), has demonstrated activity in advanced non-small-cell lung cancer (NSCLC). In single-agent studies, response rates as high as 35% have been observed; in combination with cisplatin, response rates have ranged as high as 50%, with 1-year survival rates of 33% to 58%. A critical phase III randomized trial comparing irinotecan, either alone or in combination with cisplatin, to vindesine/cisplatin, demonstrated superior survival for stage IV patients receiving irinotecan. The first North American effort to replicate the schedule used in the phase III trial (cisplatin 80 mg/m2 and irinotecan 60 mg/m2 on days 1, 8, and 15 every month) yielded a response rate of 29%, median survival time of nearly 10 months, and 1-year survival rate of 37%. A subsequent multi-institutional trial conducted through Vanderbilt Cancer Center Affiliate Network and Fox Chase Cancer Center combined both agents on a weekly schedule in an attempt to exploit their putative synergy and to potentially decrease toxicity. This schedule, which employed irinotecan 65 mg/m2 and cisplatin 30 mg/m2 both weekly x 4, was better tolerated than the monthly cisplatin combination with a higher response rate (36%), median survival (11.6 months), and 1-year survival rate (46%). Multiple phase I and phase II studies have combined irinotecan with taxanes, either alone or in concert with carboplatin (Paraplatin), yielding similar response and survival rates. Finally, a critical phase III trial from Japan has demonstrated superior outcome for irinotecan and cisplatin vs standard etoposide/cisplatin in the treatment of extensive small-cell carcinoma of the lung. At least one North American trial will determine if these results are reproducible.
Langer
C J
CJ
Thoracic Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
D000970:Antineoplastic Agents / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D002945:Cisplatin / Q000008:administration & dosage; D002986:Clinical Trials as Topic; D004357:Drug Synergism; D006801:Humans; D000077146:Irinotecan; D007564:Japan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D017239:Paclitaxel / Q000008:administration & dosage; D018714:Radiotherapy, Adjuvant; D016019:Survival Analysis; D016896:Treatment Outcome; D014481:United States
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D017239:Paclitaxel; D002945:Cisplatin; D002166:Camptothecin