Lung cancer is the leading cause of
cancer death in the United States. The majority of patients with non-small cell
lung cancers present with inoperable disease because of the presence of
metastases to regional lymph nodes or other metastatic sites. About one third of patients have stage IV disease with
metastases to distant organs at the time of diagnosis. The prognosis for these patients is very poor. With best supportive care the median survival is only 4 months and the 1-year survival rate is 10% to 15%. Current
chemotherapy combinations improve the survival and quality of life for patients with advanced
non-small cell lung cancer. With two-
drug combinations, median survival is increased to 8 months or more and 1-year survival is increased to 35% to 40%. Still, complete response rates are low and more than 80% of patients die within 1 year of diagnosis. The improvements created by current
therapies led to studies of
chemotherapy in the second-line setting.
Docetaxel has been shown to improve survival of patients who failed
platinum-based
chemotherapy and was approved by the U.S. Food and Drug Administration for
therapy in this setting. However, response rates were very low and survival very short. Therefore, new
therapies are urgently needed.
Exisulind is a novel oral
anticancer agent that holds promise for the treatment of patients with advanced
non-small cell lung cancer.
Exisulind was originally developed as a
chemoprevention agent for
colorectal cancer. Preclinical studies showed that
exisulind could prevent
polyp formation and inhibit the growth of
colorectal cancers. Subsequent preclinical studies showed that
exisulind also inhibited the growth of human breast, prostate, and
lung cancers. Phase I clinical studies showed that twice-daily oral doses could be given safely and would provide peak concentrations that were equivalent to those required for in vitro effects. These observations lead to the studies of the combination of
exisulind and
docetaxel in preclinical and clinical studies in human
lung cancer described in this article.