Inhaled Anticancer Agents

Rajiv Dhand


The search for alternative therapies for patients with surgically unresectable lung cancer continues because currently available regimens of chemotherapy, radiation therapy, and other newer treatment modalities have not made a significant impact on their grim prognosis. Inhalation therapy has intuitive advantages over systemic routes of administration because it is possible to achieve high local concentrations of therapeutic agents with minimal systemic effects. Rapid progress has been made in the ability to target aerosols to specific lung regions and in formulating inhaled therapies with lower toxicity and prolonged effects. A variety of modalities, including inhalation of immunomodulators, chemotherapeutic agents, and gene therapies, have been tested in preclinical and early-phase clinical trials, but no breakthrough treatments for lung cancer have emerged as yet. Nevertheless, these novel and promising approaches are being vigorously pursued and have the potential to improve outcomes for patients with lung cancer.

Lung cancer accounts for 14% of all new cancers and is the most common cause of cancer death in both men and women in the United States. Despite significant advances in prevention, screening, and treatment, approximately 224,000 new cases and 158,000 deaths from lung cancer were expected to occur in 2016, accounting for about 25% of all cancer deaths, in the United States (American Cancer Society 2016). The majority of new cases of lung cancer are now arising in the developing and less developed regions of the world, which have large populations of individuals who smoke cigarettes and are therefore at risk of developing lung cancer. Thus, newer, cost-effective, and well-tolerated treatments that can prolong survival among patients with lung cancer are urgently needed.

Non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and carcinoid tumors constitute the vast majority of primary lung cancers. In addition, the lungs become involved by metastatic spread of other common tumors, such as carcinomas of the breast, colon, and prostate, as well as sarcomas and melanoma. NSCLC is further broadly subclassified into adenocarcinoma, squamous cell carcinoma, large cell carcinoma, and NSCLC not otherwise specified. NSCLC accounts for the majority of patients (~75% of total cases), and most studies of inhaled anticancer treatments focus on patients with NSCLC because SCLC has often spread beyond the lungs at the time of diagnosis. Surgery, radiation therapy, and systemic chemotherapy are the primary modalities of treatment for NSCLC. The treatment of patients with early-stage disease (stages I and II by tumor-nodemetastasis (TNM) classification) is primarily surgical, but the role for systemic chemotherapy has been gradually expanding, now playing an important role in the treatment of both early-stage (stage II disease with positive lymph nodes) and locally advanced NSCLC (stage III) (Leong et al. 2014). However, systemic treatment with cytotoxic chemotherapy has the potential to produce serious adverse effects, and a significant proportion of patients may not be candidates for such therapy because of comorbidities and poor performance status.

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