The response rates of relapsed
osteosarcoma and
melanoma pulmonary
metastases to traditional i.v. chemotherapeutic regimens have been disappointing. Direct
drug delivery of
chemotherapy to the lungs could increase the
drug concentration in the
tumor area and may offer a new therapeutic approach for these patients. Previous studies demonstrated that drugs delivered to the respiratory tract in liposomal formulation resulted in high pulmonary
drug concentration, reduced systemic toxicity, and reduced dosage requirements compared with parenteral and
oral administration. To determine whether this approach has utility against pulmonary
metastases, the efficacy of
aerosol therapy with
liposome-encapsulated
9-nitrocamptothecin (L-9NC) was determined using two different experimental lung
metastasis models. C57BL/6 mice were treated the day after the i.v. injection of
B16 melanoma cells with
aerosol L-9NC for 1 h (153 microg 9-nitrocamptothecin/kg) for 5 days per week for up to 3 weeks.
Aerosol L-9NC treatment resulted in a reduction in lung weights (P = 0.005) and number of
tumor foci (P < 0.001). Visible
tumor nodules were fewer and smaller in the 9-nitrocamptothecin-treated group than in untreated control mice (P < 0.001). Using a newly developed human
osteosarcoma experimental
metastasis model in nude mice, we demonstrated that
aerosol L-9NC was also effective against established lung
metastases.
Aerosol therapy initiated on the ninth week after i.v.
tumor injection and continued for 8 or 10 weeks produced highly significant reductions in the number of animals with both visible and microscopic disease (P < 0.02), the total number of
tumor foci in the lungs (P < 0.005), and the size of the individual
tumor nodules (P < 0.02). These data suggest that L-9NC
aerosol therapy may offer significant advantage over existing methods in the treatment of
melanoma and
osteosarcoma pulmonary
metastases.