ZD1839, a selective epidermal growth factor receptor tyrosine kinase inhibitor, alone and in combination with radiation and chemotherapy as a new therapeutic strategy in non-small cell lung cancer.
The epidermal growth factor receptor is overexpressed in a majority of non-small cell lung cancers and has been associated with a poor prognosis. Preclinical studies have shown that ZD1839, an oral anilinoquinazoline, targets the epidermal growth factor receptor-associated tyrosine kinase, reversibly inhibiting critical downstream signaling and resulting in cancer cell growth arrest. Potent antitumor effects have been observed in human lung tumor xenograft models. Preclinical studies have shown additive to synergistic effects when ZD1839 is combined with radiation or chemotherapy in colon, head and neck, and non-small cell lung cancers. Phase I clinical trials have shown modest dose-related toxicity, and antitumor activity has been reported in a variety of malignancies including lung cancer. Future studies will certainly combine ZD1839 with chemotherapy or radiation. ZD1839 also may be effective as a chemoprevention agent because premalignant lesions often overexpress epidermal growth factor receptor.
Raben
David
D
Department of Radiation Oncology, University of Colorado Comprehensive Cancer Center, Denver, CO 80010-0510, USA.
Helfrich
Barbara A
BA
Chan
Dan
D
Johnson
Gary
G
Bunn
Paul A
PA
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000532:radiotherapy; D002453:Cell Cycle / Q000187:drug effects; D018890:Chemoprevention; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000187:drug effects / Q000378:metabolism*; D000077156:Gefitinib; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D011799:Quinazolines / Q000008:administration & dosage / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014183:Transplantation, Heterologous; D015854:Up-Regulation
D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib