Session Speaker

Aerosol Gemcitabine: Preclinical Safety and in vivo Antitumor Activity in Osteosarcoma-Bearing Dogs
Carlos O Rodriguez, Torrie A. Crabbs, Dennis W. Wilson, Virginia A. Cannan, Katherine A. Skorupski, Nancy Gordon, Nadya Koshkina, Eugenie Kleinerman, and Peter M. Anderson
USA

Osteosarcoma is the most common skeletal malignancy in the dog and in children. Although chemotherapy improves survival time, death continues to be attributed to metastases. The purpose of this study is to assess the safety of aerosol chemotherapy delivery in dogs and secondly to evaluate Fas expression in the metastasis.

We examined the histopathological effects of aerosol gemcitabine against spontaneous osteosarcoma pulmonary metastasis in this relevant large animal tumor model. Six hundred and seventy-two one-hour doses of aerosol gemcitabine were delivered. The treatment was well tolerated by these twenty subjects with osteosarcoma. Aerosol treatment resulted in extensive, predominately central, intratumoral necrosis. Fas expression decreased in pulmonary metastases as compared to the primary tumor (p = 0.008). Fas expression increased in the metastatic foci after aerosol gemcitabine as compared to untreated lung metastases (p=0.0075) and even was higher than the primary tumor (p=0.025). Increased apoptosis staining was detected in aerosol gemcitabine treated metastasis as compared to untreated controls (p = 0.028).

The results from this pivotal translational study support the concept that aerosol gemcitabine may be useful against pulmonary metastases of osteosarcoma. Additional studies that evaluate the aerosol route of administration of gemcitabine in humans should be safe and are warranted.