Irinotecan in combined-modality therapy for locally advanced non-small-cell lung cancer

The management of non-small-cell lung cancer is undergoing rapid evolution. Although the advent of combined-modality therapy has led to improved survival, most patients eventually succumb to the disease. The arrival of 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 a variety of solid tumors, including non-small-cell lung cancer. It is believed to act by stabilizing the topoisomerase-DNA complex formed during diverse cellular processes, including replication and transcription. A considerable body of evidence also demonstrates that camptothecin and its derivatives possess substantial radiosensitization properties. This article will review the in vitro and in vivo data on irinotecan's ability to render tumors more susceptible to ionizing radiation. It will then focus on experience with irinotecan and thoracic radiation in the treatment of non-small-cell lung cancer, which has yielded acceptable toxicity results and response rates in excess of 60% in early trials. It is hoped that newer treatment strategies--such as the combination of radiation and irinotecan in lung cancer--will significantly impact cure rates in the future.