Lymphoma is one of the most common and fatal cancers in dogs. Most dogs treated with chemotherapy go into remission, but the cancer quickly develops drug resistance and recurs. Chemotherapy generally works by initiating apoptosis, a normal process in which cells undergo programmed death. Apoptosis occurs throughout life and is critical for developing and maintaining healthy tissues, but cancer cells develop ways to avoid apoptosis, which allows them to grow and survive in an uncontrolled fashion. Researchers studied a novel compound, PAC-1, that has been shown to induce apoptosis in tumor cells without the presence of chemotherapy. This study attempted to evaluate the safety, dosing and efficacy of PAC-1 in dogs with lymphoma. The researchers felt that this compound held great promise for the treatment of lymphoma and other cancers.
Dogs enrolled in this clinical trial had not responded to other therapies or had owners who could not afford other therapies. PAC-1 works via a different mechanism than traditional chemotherapy and based on preliminary data, it showed promise as a revolutionary treatment for dogs with cancer. Recent study developments, however, indicate that the drug cannot be used safely at the levels needed to produce an anticancer effect. Because of these developments, this clinical trial was discontinued. It is important to note that preliminary data in laboratory cell-line models were promising and that the drug was well tolerated in the initial three dogs that were treated. However, as the study progressed, there was unexpected neurotoxicity. The researchers quickly determined that PAC-1 is not safe for dogs at blood concentrations needed to be therapeutic and therefore terminated the study.
Although the results were not what we hoped for, this study has provided critical knowledge about PAC-1. First, researchers clearly determined that PAC-1 isn’t safe for dogs. It can cause severe and unpredicted neurotoxicity and, therefore, shouldn’t be pursued as a treatment for canine lymphoma. Second, similar drugs are in development, and these findings indicate the need for safer formulations of these drugs for future studies.
NOTE: The entire amount of our co-sponsorship was transferred to another research study and therefore was not lost or wasted by the early termination of this research project.
Co-sponsored with the Morris Animal Foundation, Grant Number: D09CA-082
Dr. Laura D. Garrett,
DVM, Dipl. ACVIM (Oncology)
University of Illinois