Inhaled Chemotherapeutic Agents
Treatment with aerosolized 5-FU, doxorubicin, 9-NC, liposomal paclitaxel, and platinum agents has shown activity against lung cancer and metastasis to the lung in preclinical studies. Subsequent phase I/II clinical trials have assessed the safety and anticancer effect of several chemotherapeutic agents, including inhaled 5-FU, GEM, 9-NC, doxorubicin, and platinum agents (Table 5.1).
5-FU is a fluoropyrimidine that acts as an antimetabolite inhibiting DNA and ribonucleic acid (RNA) synthesis. In the first study of inhaled chemotherapy in humans, Tatsumura and colleagues observed that 5-FU concentrations in the airways and regional lymph nodes were at therapeutic levels, whereas only a trace of the drug was detected in the serum (Tatsumura et al. 1993). Interestingly, the levels of 5-FU were significantly higher in the tumor tissue than in the normal lung tissue. Six of 10 patients with unresectable lung cancer who were previously untreated and received inhaled 5-FU responded to therapy with no significant adverse effects from these treatments (Tatsumura et al. 1993).
GEM belongs to the same class of drugs as 5-FU. Inhaled GEM administered once a week for 9 weeks to 11 patients with lung cancer resulted in a partial response in one patient and stable disease in four patients (Lemarie et al. 2011).