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Eur Respir J 2005; 26:657-661
Copyright ©ERS Journals Ltd 2005

Aerosol delivery of chemotherapy in an orthotopic model of lung cancer

F. Gagnadoux1,2, A. L. Pape1,3, E. Lemarié1, S. Lerondel3,5, I. Valo4, V. Leblond1, J-L. Racineux2 and T. Urban2

1 Groupe de pneumologie, INSERM, U618, IFR135, Faculté de Médecine, and 5 Biopharmconsulting –ARAIR, Tours, 2 Dépt de Pneumologie, CHU, and 4 Laboratoire d'anatomopathologie, Centre régional de lutte contre le cancer, Angers, and 3 CDTA-CNRS, Orléans, France.

CORRESPONDENCE: F. Gagnadoux, Dépt de Pneumologie, CHU, 4 rue Larrey, 49033 Angers Cedex, France. Fax: 33 241354974. E-mail: frgagnadoux{at}chu-angers.fr

Keywords: Aerosol, chemotherapy, gemcitabine, lung cancer, orthotopic model

Received: February 15, 2005
Accepted June 14, 2005

The aim of this study was to evaluate the effect on tumour growth of gemcitabine delivered by aerosol in an orthotopic model of lung carcinoma.

Large cell carcinoma (NCI-H460) cells were implanted intrabronchially in 24 male BALB/c nude mice on day (d) 0. Aerosols were delivered once a week from d1 to d29 using an endotracheal sprayer. Altogether, 16 animals received gemcitabine at 8 (n = 8) and 12 mg·kg–1 (n = 8), and eight received a vehicle aerosol. Animals were sacrificed on d36 for histological examination.

All animals in the vehicle group developed a large infiltrating carcinoma. Comparatively, four of 13 (31%) animals treated with gemcitabine had no visible tumour and nine of 13 (69%) had a smaller carcinoma with a mean±SEM largest tumour diameter of 2.05±0.7 versus 5±0.3 mm in the vehicle group. Gemcitabine was well tolerated at 8 mg·kg–1. At 12 mg·kg–1, three cases of fatal pulmonary oedema were observed, prompting a dose reduction to 8 mg·kg–1 in the remaining animals. A dose effect was observed, with more marked tumour growth inhibition in the animals treated at 12 mg·kg–1 on d1 and d8.

In conclusion, in this study, an animal model of aerosolised chemotherapy in lung cancer was developed and demonstrated inhibition of orthotopic tumour growth by aerosol delivery of gemcitabine.






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