The Emerging World Role of Irinotecan in Lung Cancer

ABSTRACT: Irinotecan (CPT-11, Camptosar), either alone or in combinationwith cisplatin (Platinol), has demonstrated activity in advanced non-small-celllung cancer (NSCLC). In single-agent studies, response rates as high as 35% havebeen observed; in combination with cisplatin, response rates have ranged as highas 50%, with 1-year survival rates of 33% to 58%. A critical phase IIIrandomized trial comparing irinotecan, either alone or in combination withcisplatin, to vindesine/cisplatin, demonstrated superior survival for stage IVpatients receiving irinotecan. The first North American effort to replicate theschedule used in the phase III trial (cisplatin 80 mg/m2 and irinotecan 60mg/m2on days 1, 8, and 15 every month) yielded a response rate of 29%, mediansurvival time of nearly 10 months, and 1-year survival rate of 37%. A subsequentmulti-institutional trial conducted through Vanderbilt Cancer Center AffiliateNetwork and Fox Chase Cancer Center combined both agents on a weekly schedule inan attempt to exploit their putative synergy and to potentially decreasetoxicity. This schedule, which employed irinotecan 65 mg/m2 and cisplatin 30mg/m2 both weekly × 4, was better tolerated than the monthly cisplatincombination with a higher response rate (36%), median survival (11.6 months),and 1-year survival rate (46%). Multiple phase I and phase II studies havecombined irinotecan with taxanes, either alone or in concert with carboplatin(Paraplatin), yielding similar response and survival rates. Finally, a criticalphase III trial from Japan has demonstrated superior outcome for irinotecan andcisplatin vs standard etoposide/cisplatin in the treatment of extensivesmall-cell carcinoma of the lung. At least one North American trial willdetermine if these results are reproducible. [ONCOLOGY 15(Suppl 8):15-21, 2001]

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