FORT LAUDERDALE--Evaluations of new treatments using traditional endpoints such as response or survival may not be appropriate in advanced solid tumors that are highly symptomatic but essentially incurable, Howard A. Burris III, MD, said at the National Comprehensive Cancer Network conference.
Alternative quality of life endpoints may prove useful in evaluating drugs for these tumors, not only in clinical trials but also in guidelines development.
Dr. Burris and his group at the Cancer Therapy and Research Center, San Antonio, were involved in developing novel endpoints for studies of gemcitabine(Drug information on gemcitabine) (Gemzar) in advanced pancreatic cancer that led to FDA approval of the agent.
Pancreatic cancer is highly lethal, with 86% of patients dying within a year of diagnosis, Dr. Burris said. But a unique aspect of the disease is that almost all patients experience the same symptoms--weight loss, jaundice, visceral pain, anor-exia, nausea, and depression. "Thus, it was an appropriate solid tumor model to evaluate clinical benefit as an endpoint."
Previous discussions between NCI and FDA on using novel endpoints paved the way for the pivotal gemcitabine trials.
The San Antonio group's goal was to develop a "systematic and sensitive method to assess the palliative benefits of chemotherapy," Dr. Burris said. They called this the clinical benefit response, measured as clinical benefit response rate. The gemcitabine studies would also look at secondary endpoints such as tumor response rate, time to disease progression, and survival as a means of validating the symptomatic endpoints.
Setting the Parameters
The primary measurement of clinical benefit response would be the compilation of two factors--pain scales that measured analgesic consumption and pain intensity to produce an overall pain evaluation, and traditional Karnofsky performance status (PS) measures.