Rationale and Dose-Finding Studies of the Combination of Irinotecan and a Taxane on a Weekly Schedule

ABSTRACT: Cisplatin (Platinol)-based chemotherapy has been the standardsystemic therapy for both non-small-cell and small-cell lung cancer for thepast 2 decades, though the efficacy and benefit remain modest. Recently, severalnovel agents have been introduced that have single-agent activity comparable tocisplatin and offer the possibility of improved therapy for lung cancer.Camptothecin and taxane derivatives are associated with both differentmechanisms of action and nonhematologic toxicities, and have demonstratedadditive or synergistic activity when used in combination in preclinicalstudies. We review pertinent clinical studies of these agents in lung cancer andpresent our experience in combining irinotecan (Camptosar, CPT-11) with taxaneson a weekly schedule in dose-finding and efficacy studies. When chemotherapy isdelivered for 4 consecutive weeks followed by a 2-week rest, hematologictoxicity is dose limiting and most prominent during weeks 3 and 4. Doseintensification is feasible if the schedule is modified so the chemotherapy isgiven on days 1 and 8, with cycles repeated every 3 weeks. The most commonnonhematologic toxicities remain asthenia, neuropathy, and diarrhea. Futurestudies will explore and better define the role of these drug combinations inthe treatment of lung cancer. [ONCOLOGY 15(Suppl 1):25-30, 2001]IntroductionCisplatin (Platinol)-based chemotherapyhas been the foundation of the treatment of lung cancer for over 2 decades.Several new classes of agents, or analogs of existing drugs, that havesingle-agent activity comparable to cisplatin have recently been introduced. Twoclasses of new drugs that have significant activity in both small-cell and non-small-celllung cancer are the camptothecins and the taxanes.

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