After an NCI-led Phase II study combining the vaccine with Interleukin-2 (IL-2) showed response rates of 42 percent in metastatic melanoma patients, a Phase III randomized trial with the two agents opened more than a decade ago.
Conducting a large, multi-institutional trial with IL-2, however, had its own set of unique challenges, explained Hwu, as not all cancer centers and community hospitals are capable of administering the immunotherapy. A highly specialized therapy associated with such significant side effects as low blood pressure and capillary leak syndrome, which poses risks to the heart and lung, IL-2 is often delivered in intensive care units. Just last month, M. D. Anderson opened a special in-patient unit exclusively designed for the drug's delivery; before, the institution was offering the therapy in its ICU.
In the Phase III trial, 185 patients at 21 centers across the country were enrolled in the study. All had advanced metastatic melanoma and were stratified for cutaneous metastasis, a known indicator of response to IL-2. Patients were randomized to receive either high dose IL-2, or IL-2 and vaccine. In the IL-2 arm, 94 patients were enrolled and 93 were treated and evaluated for response; 91 were enrolled and 86 treated and evaluated in the IL-2 and vaccine arm.
The study found that those who received the vaccine had a significant response rate, 22.1 percent, and progression-free survival, 2.9 months, compared to 9.7 percent and 1.6 months respectively in those that did not. While not statistically significant, the median overall survival for those receiving vaccine trended positive, 17.6 months vs. 12.8 months.
"This is one of the first positive, randomized vaccine trials in cancer and the findings represent a significant step forward for treatment
|Contact: Laura Sussman|
University of Texas M. D. Anderson Cancer Center