Endobronchial Intratumoral Chemotherapy (EITC) for Improved Treatment of Lung Cancer

Abstract

The safety and efficacy of conventional intravenous chemotherapy is severely compromised by systemic drug toxicity. Despite significant advances in cancer diagnosis and therapy, CDC estimates for the past 20 years indicate little progress in reducing mortality for breast, lung, and colorectal cancers. Indeed, the mortality for lung cancer has increased more than 75%. Antibody targeting and gene therapies remain exploratory. New, improved, and clinically practical treatment concepts are needed. Reported here is progress, from the laboratory to clinical application, for a new localized cancer chemotherapy paradigm; the direct intratumoral (IT) injection of cytotoxic drugs. One major aspect of this research has been the synthesis of albumin, casein, and DNA microspheres loaded with mitoxantrone designed for IT injection. In murine models of lung, breast, and ovarian cancers significantly prolonged survival and cures have been demonstrated. A major clinical outcome of IT studies has been a new paradigm for lung cancer therapy, endobronchial intratumoral chemotherapy (EITC). This has been achieved via a unique University of Istanbul/University of Florida collaboration. Pioneering clinical studies conducted in Istanbul used bronchoscopic IT injections of cisplatin, mitoxantrone, and 5-FU in non-small cell lung (NSCL) cancer patients. EITC has proven remarkably effective in patients presenting with bronchial tumor obstruction. Reduced morbidity and mortality were realized with enhanced patient quality of life and without the toxic complications associated with systemic chemotherapy.KeywordsIntratumoral chemotherapymicrospheresbronchoscopylung cancerdrug delivery