9-nitrocamptothecin liposome aerosol treatment of melanoma and osteosarcoma lung metastases in mice

Citation
Nv. Koshkina et al., 9-nitrocamptothecin liposome aerosol treatment of melanoma and osteosarcoma lung metastases in mice, CLIN CANC R, 6(7), 2000, pp. 2876-2880
Citations number
17
Categorie Soggetti
Oncology
Journal title
CLINICAL CANCER RESEARCH
ISSN journal
10780432 → ACNP
Volume
6
Issue
7
Year of publication
2000
Pages
2876 - 2880
Database
ISI
SICI code
1078-0432(200007)6:7<2876:9LATOM>2.0.ZU;2-M
Abstract
The response rates of relapsed osteosarcoma and melanoma pulmonary metastas es to traditional i.v. chemotherapeutic regimens have been disappointing. D irect drug delivery of chemotherapy to the lungs could increase the drug co ncentration in the tumor area and may offer a new therapeutic approach for these patients. Previous studies demonstrated that drugs delivered to the r espiratory tract in liposomal formulation resulted in high pulmonary drug c oncentration, reduced systemic toxicity, and reduced dosage requirements co mpared with parenteral and oral administration, To determine whether this a pproach has utility against pulmonary metastases, the efficacy of aerosol t herapy with liposome-encapsulated 9-nitrocamptothecin (L-9NC) was determine d using two different experimental lung metastasis models. C57BL/6 mice wer e treated the day after the i.v. injection of B16 melanoma cells with aeros ol L-9NC for 1 h (153 mu g 9-nitrocamptothecin/kg) for 5 days per week for up to 3 weeks, Aerosol L-9NC treatment resulted in a reduction in lung weig hts (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 un treated control mice (P < 0.001), Using a newly developed human osteosarcom a experimental metastasis model in nude mice, we demonstrated that aerosol L-9NC was also effective against established lung metastases, Aerosol thera py 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 anim als 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 tumo r nodules (P < 0.02), These data suggest that L-9NC aerosol therapy may off er significant advantage over existing methods in the treatment of melanoma and osteosarcoma pulmonary metastases.