Nancy Gordon, MD
University of Texas, MD Anderson Cancer Center

Osteosarcoma (OS) is the most common bone tumor in children. It almost always spreads to their lungs and these pulmonary lesions are the main cause of their deaths. The 2-year metastases-free survival rate has remained stagnant for more than 15 years.

According to many animal studies, local aerosol delivery of gemcitabine (GCB) allows for a better drug concentration in the lung with less systemic side effects and fewer metastases. Systemic delivery does not achieve therapeutic levels in the lungs. The safety of aerosol GCB was demonstrated in adult patients with lung cancer in Europe. That study did not include children.

OS treatment sequence includes chemotherapy, then surgery, and then more chemotherapy. The treatment delay between surgery and the second round of chemotherapy may impact survival. The researchers are hopeful that the introduction of a less toxic but target-specific aerosol during this gap period may prolong survival.

This proposed phase I trial will use an aerosolized chemotherapy delivery system to treat OS lung metastases in patients 12 to 50 years of age with gemcitabine (GCB). It will include the collection of some tumor specimens. The researchers will additionally evaluate the role of chemotherapeutics on cancer cells’ autophagy. Besides directly killing cancers cells, chemotherapy may also stimulate cells to begin their natural cycle of death and regeneration. [Awarded 2016]


Clinical Description
Osteosarcoma (OS) is the most common bone tumor in children. It spreads almost always to the lungs.
Lung metastasis is the main cause of death in these patients. The 2-year metastases free survival rate has
remained stagnant for more than 15 years. An aerosolized delivery of chemotherapy, specifically
Gemcitabine (GCB) to treat OS lung metastases, will be used. Local delivery allows for a better drug
concentration in the lung and less side effects. This has been demonstrated to be effective in our pre-clinical
human OS mouse models. Effectiveness of this approach was also confirmed by other investigators in
baboons and dogs with OS lung metastases. Furthermore, feasibility and safety of aerosol GCB was
demonstrated in adult patients with lung cancer in Europe. However, this study did not include children.

The proposed study aims to complete a Phase I trial of aerosol GCB in patients 12 to 50 years of age with lung metastases. Testing of feasibility and safety of this approach will be conducted as well as obtaining tumor specimens to study some of the mechanisms implicated in tumor cells therapeutic response and resistance.

This is a novel mechanism of drug delivery. Specifically, it provides a unique opportunity as the first step towards using nebulized or aerosol therapy as regional treatment for patients with OS lung metastases. In addition, the use of this less toxic approach could be implemented during the gap period between the time surgery is completed and chemotherapy is reinitiated in patients with OS. Perhaps this will translate in an improved survival. [Awarded 2016]