ABSTRACT

There are several compelling reasons why pulmonary delivery of aerosolized chemotherapy for the direct local treatment of lung tumors is likely to provide advancements in therapy. For other diseases affecting the lungs, significant improvements in therapy have been achieved using inhalation aerosols. Asthma was the first example where the pharmacokinetic and pharmacodynamic advantage of aerosol drug delivery resulted in critical improvements in therapy. These improvements include rapid onset therapy (i.e. bronchodilators) and significant decreases in systemic side effects (i.e. corticosteroids). Subsequently, inhalation aerosols have been applied to other local diseases of the lungs including cystic fibrosis, chronic obstructive pulmonary disease, tuberculosis, pneumocystis carinii pneumonia, and pulmonary hypertension. It is surprising therefore, that scant attention has been paid to reapplying these same basic principles of pharmacokinetic advantage to the leading cause of cancer death, lung cancer. In this chapter, we outline the rationale, potential limitations, and previous investigations of pulmonary delivery of chemotherapy. Those studies that have investigated regional administration of chemotherapy agents using aerosols are reviewed with specific emphasis placed on the results of some of the first clinical trials

in this area that we have performed. Based on this data, we also explore the potential advantages and limitations for the aerosol delivery of anti-cancer agents. Finally, issues are examined for future clinical translation of therapies in development.