Pulmonary metastases are the leading cause of death in patients with osteosarcoma. Resection of the lung metastases is potentially curative, but surgery is not feasible for some patients. Many patients with lung metastases therefore receive systemic chemotherapy, which has significant side effects and, in this population, limited survival benefits. To reduce side effects and improve outcomes for patients with lung metastases from osteosarcoma and other cancers, researchers have developed a novel approach that delivers aerosolized chemotherapy directly to the lungs.
The potential benefit of aerosolized chemotherapy was established in pre-clinical studies by researchers including Eugenie Kleinerman, M.D., and Nancy Gordon, M.D., a professor and assistant professor, respectively, in the Division of Pediatrics at The University of Texas MD Anderson Cancer Center. “We found that we can administer a much lower dose by aerosol than what is usually given systemically and achieve greater benefit, thus decreasing the systemic toxic effects of the treatment,” Dr. Gordon said.
In the preclinical studies, the aerosolized cytotoxic agent that was most effective against lung metastases from osteosarcoma was gemcitabine. Normally given intravenously, gemcitabine is approved by the U.S. Food and Drug Administration for the treatment of several cancers and has shown activity against various types of sarcoma in clinical trials. On the basis of the preclinical findings, a clinical trial of aerosolized gemcitabine for children and adults with solid tumors and lung metastases is now enrolling patients at MD Anderson.
The phase I trial (No. 2015-0720) is open to patients 12–50 years old who have lung metastases from osteosarcoma or other solid tumors and no proven survival-extending treatment options. “Because we’re studying the feasibility, safety, and toxicity of this treatment strategy rather than efficacy, we’re including patients with all types of solid tumors who have lung metastases,” said Najat Daw Bitar, M.D., a professor in the Division of Pediatrics and the trial’s principal investigator. She added that patients who have asthma or poor lung function for other reasons are excluded from the trial.
Patients in the trial receive aerosolized gemcitabine twice weekly for up to 12 28-day cycles. The primary outcome measures are the maximum tolerated dose and toxic effects. The researchers will also study the drug’s pharmacokinetics and tumor response according to Response Evaluation Criteria In Solid Tumors, version 1.1.
Once the maximum tolerated dose is established, the trial will enroll only patients with osteosarcoma. “We want to get preliminary information to see if we should pursue a bigger study in patients with osteosarcoma,” Dr. Daw Bitar said. “But this novel therapeutic strategy doesn’t necessarily only apply to lung metastases from osteosarcoma. It can potentially be used in lung metastases from any solid tumors that respond to gemcitabine.”
“We monitor patients’ pulmonary function throughout the trial,” Dr. Gordon said. To facilitate this monitoring, patients are provided with a spirometer and a tablet. Before coming to the clinic on the day of each treatment, patients answer a questionnaire about their current health using the tablet and blow into the spirometer. The data from the questionnaire and spirometer are transferred to the patients’ physicians via a Web portal. A 10% or greater decline in pulmonary function is immediately investigated and, if the decline persists, could result in treatment cessation.
Several precautions are taken to ensure that hospital staff and patients’ family members are not exposed to the aerosolized cytotoxic agent during treatment. Treatment is given on an outpatient basis at MD Anderson with the patient under a plastic canopy in a negative pressure room. The patient receives gemcitabine via a nebulizer that delivers treatment only when the patient inhales. Furthermore, the nurses administering the treatment wear filtration masks and protective gloves and garments.
“If we can prove that the treatment is safe and does not pose a risk to caregivers, our ultimate goal is for the patients to get their therapy at home,” Dr. Daw Bitar said.
For more information, contact Dr. Najat Daw Bitar at 713-792-6315 or firstname.lastname@example.org or Dr. Nancy Gordon at 713-563-5418 or email@example.com. To learn more about the clinical trial of aerosolized gemcitabine for patients with lung metastases, visit www.clinical trials.org and search for study No. 2015-0720.