Judah Folkman R.I.P.

I just heard that Judah Folkman just passed away at the age of 74. That is a name that is not widely known outside the scientific world, although a couple of years ago an excellent book –Dr. Folkman’s War – was written about him and his work.

His major work and his enduring legacy was in the field of angiogenesis: the production of new blood vessels. In the 1960s he came up with the idea that a way to kill tumors was to starve them of the blood supply that they need to survive. He was initially ridiculed, but history is now proving him correct. I got to know him twenty years ago after publishing a paper in which I described the discovery of a growth factor that is involved in the production of new blood vessels at the back of the eye in people with diabetes. Judah was very supportive and we had many good discussions about the potential role of angiogenesis not only in tumors and diabetic retinopathy, but also in diseases like rheumatoid arthritis and psoriasis.

Last November, at the 12th Annual Society for Neuro-Oncology Meeting in Dallas, researchers from the University of Virginia and several other leading brain tumor centers in the United States presented data on the successful use of an inhibitor of angiogenesis in the treatment of glioblastoma multiforme (GBM), the most common form of primary brain cancer. It is hard to treat, and if it recurred after surgery, radiation and/or chemotherapy there was often not much to be done.

Building on Judah’s work, they wanted to see if they could inhibit vascular endothelial growth factor (VEGF) that has an important role in the disease. VEGF fosters the growth of a tumor by
stimulating the growth of new blood vessels to feed it. According to earlier studies, bevacizumab (BV) (Avastatin), a humanized monoclonal antibody that specifically targets VEGF, in combination with irinotecan (also called CPT-11) could have a role in recurrent glioblastoma multiforme. The researcher was an attempt to establish the clinical benefit of BV, both alone and in combination with CPT-11, in a multicenter, randomized phase II trial.

The results were very promising, substantially exceeded the pre-specified thresholds set for this work.

They looked at 6-month progression-free survival (PFS) defined as no clinical or MRI tumor growth and the objective response rate (ORR), which measures tumor shrinkage. Secondary endpoints included safety and survival. Response assessments were conducted by an independent radiographic facility that did not know which patients had been treated. All patients were followed for 24 weeks to determine efficacy and safety.

When taking BV, 35.6 percent of patients on average had a 6-month survival with no progression of their cancer, and an objective response rate of 21.2 percent on average.

The combination of BV and CPT was even more effective, with results of 51 percent and 34.1 percent, respectively.

The investigator group found similar results when they evaluated the patients. Those results showed that 44.7 percent of patients on average had a 6-month survival with no progression of their cancer, and an objective response rate of 38.8 percent on average. The combination therapy yielded results of 60.9 percent and 46.3 percent, respectively.

The surviving patients have remained in the study and are still being treated and followed, so we shall be seeing some longer-term results in the future.

In the United States bevacizumab has already been approved for the treatment of metastatic colon cancer and most forms of metastatic non-small cell lung cancer.

This is very encouraging research and a fitting tribute to a genuine medical pioneer.