TY - JOUR
T1 - Topoisomerase I inhibitors in the combined modality therapy of lung cancer
AU - Choy, H.
AU - Kim, J. S.
AU - Pyo, H.
AU - MacRae, R.
N1 - Funding Information:
The authors would like to thank Laura Tyree for her help in the preparation of this manuscript. Dr. Rob MacRae is a research fellow funded in part by the Canadian Cancer Society (Ontario) as the Gordon Richards Fellowship recipient.
PY - 2000
Y1 - 2000
N2 - Locally advanced non-small-cell lung cancer (NSCLC) represents 30%-40% of all pulmonary malignancies. Despite the fact that the disease is confined to the chest, most patients will eventually succumb to their disease. Therefore, the management of NSCLC is undergoing rapid evolution with hope of improving overall survival. The arrival of a new generation of chemotherapeutic agents, including the taxanes, gemcitabine, and topoisomerase inhibitors such as irinotecan and topotecan, offers the hope of real advances against this malignancy. Irinotecan and topotecan are camptothecin derivatives that are felt to exert their cytotoxic effects by targeting topoisomerase I. It is believed that topoisomerase I inhibitors stabilize a DNA-topoisomerase I cleavable complex, and interactions between this complex and the replication machinery may lead to cell death. There is a significant volume of in vitro and in vivo data demonstrating that these topoisomerase I inhibitors also act as radiosensitizers. Early clinical data with topotecan suggests that it is a more active agent in small-cell lung cancer than it is in NSCLC despite a common mechanism of action with irinotecan. With the increasing data that exist on the improved outcome with concurrent chemoradiation treatment for malignancies including lung cancer and head and neck cancers, there is an impetus to pursue the addition of other drugs that can radiosensitize tumors and further improve local control. Irinotecan is undergoing early clinical trials in the combined modality setting in several different disease sites. This paper will review the in vitro and in vivo data on the ability of irinotecan and topotecan to render tumors more susceptible to ionizing radiation. It will then focus on the experience with both drugs and thoracic radiation in the treatment of NSCLC, in which irinotecan 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 topoisomerase I inhibitors in lung cancer, will have a significant impact on cure rates in the future.
AB - Locally advanced non-small-cell lung cancer (NSCLC) represents 30%-40% of all pulmonary malignancies. Despite the fact that the disease is confined to the chest, most patients will eventually succumb to their disease. Therefore, the management of NSCLC is undergoing rapid evolution with hope of improving overall survival. The arrival of a new generation of chemotherapeutic agents, including the taxanes, gemcitabine, and topoisomerase inhibitors such as irinotecan and topotecan, offers the hope of real advances against this malignancy. Irinotecan and topotecan are camptothecin derivatives that are felt to exert their cytotoxic effects by targeting topoisomerase I. It is believed that topoisomerase I inhibitors stabilize a DNA-topoisomerase I cleavable complex, and interactions between this complex and the replication machinery may lead to cell death. There is a significant volume of in vitro and in vivo data demonstrating that these topoisomerase I inhibitors also act as radiosensitizers. Early clinical data with topotecan suggests that it is a more active agent in small-cell lung cancer than it is in NSCLC despite a common mechanism of action with irinotecan. With the increasing data that exist on the improved outcome with concurrent chemoradiation treatment for malignancies including lung cancer and head and neck cancers, there is an impetus to pursue the addition of other drugs that can radiosensitize tumors and further improve local control. Irinotecan is undergoing early clinical trials in the combined modality setting in several different disease sites. This paper will review the in vitro and in vivo data on the ability of irinotecan and topotecan to render tumors more susceptible to ionizing radiation. It will then focus on the experience with both drugs and thoracic radiation in the treatment of NSCLC, in which irinotecan 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 topoisomerase I inhibitors in lung cancer, will have a significant impact on cure rates in the future.
KW - Combined modality therapy
KW - Irinotecan
KW - Non-small-cell lung cancer
KW - Thoracic radiation
KW - Topoisomerase I inhitors
KW - Topotecan
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U2 - 10.3816/clc.2001.s.006
DO - 10.3816/clc.2001.s.006
M3 - Article
C2 - 14725728
AN - SCOPUS:0034953469
SN - 1525-7304
VL - 2
SP - S34-240
JO - Clinical lung cancer
JF - Clinical lung cancer
IS - SUPPL. 2
ER -