Irinotecan in Combined-Modality Therapy for Locally Advanced Non-Small-Cell Lung Cancer

ABSTRACT: The management of non-small-cell lung cancer is undergoingrapid evolution. Although the advent of combined-modality therapy has led toimproved survival, most patients eventually succumb to the disease. The arrivalof a new generation of chemotherapeutic agents—including the taxanes,gemcitabine (Gemzar), and topoisomerase inhibitors such as irinotecan(Camptosar, CPT-11)—offers the hope of advances against this malignancy.Irinotecan, a camptothecin derivative, has shown impressive activity in avariety of solid tumors, including non-small-cell lung cancer. It is believedto act by stabilizing the topoisomerase-DNA complex formed during diversecellular processes, including replication and transcription. A considerable bodyof evidence also demonstrates that camptothecin and its derivatives possesssubstantial radiosensitization properties. This article will review the in vitroand in vivo data on irinotecan’s ability to render tumors more susceptible toionizing radiation. It will then focus on experience with irinotecan andthoracic radiation in the treatment of non-small-cell lung cancer, which hasyielded acceptable toxicity results and response rates in excess of 60% in earlytrials. It is hoped that newer treatment strategies—such as the combination ofradiation and irinotecan in lung cancer—will significantly impact cure ratesin the future. [ONCOLOGY 15(Suppl 1):31-36, 2001]