Not surprisingly, we got a different perspective on the melanoma vaccine trials when we consulted with Dr. Sharfman at Johns Hopkins yesterday. We haven’t decided yet whether Robert will enter the trial, but it no longer sounds like such a bad option.

One concern raised by Dr. Venna at Washington Hospital Center is that some patients in the Hopkins trial are getting the vaccine along with a another drug, cyclophosphamide, which is known to have serious side effects when used at higher doses as a therapy against some cancers. As Dr. Sharfman described its use in this trial, the dose is low enough that it should not cause harm or bad side effects in otherwise healthy patients.

The vaccine, known as melanoma GVAX, is made from cultured melanoma cells that have been modified to secrete a natural substance (granulocyte macrophage colony stimulating factor, or GM-CSF) that activates immune cells in the body. It is similar to vaccines that have been used in trials against other types of cancer over the last 15 years without serious side-effects.

Dr. Venna did not express concerns about the vaccine itself, although he did note that it hasn’t been proven effective yet. Rather, his concern was about exposing Robert to cyclophosphamide, which can cause unpleasant and dangerous side effects.

Dr. Sharfman’s explanation was that the dosage of cyclophosphamide given to fight lymphoma, multiple myeloma, and leukemia is 10 times the dose used in conjunction with cancer vaccines. He said no serious side effects have been seen when it is used at this low dose. He also explained the purpose for giving it with GVAX is to knock out lymphocytes that interfere with the immune response the vaccine is aiming to produce.

As I understood his explanation, some mechanisms of the immune system that keep it from going overboard are associated with certain lymphocytes, called regulatory cells. In doing what they are supposed to do, these cells are keeping the vaccine from working. Researchers believe that a low dose of cyclophosphamide will knock out those regulatory cells without knocking out other white cells, neutrophils, red cells and platelets in the blood. The overall effect, he said, is to give the immune system a bigger boost than the vaccine alone would produce.

From Dr. Sharfman’s perspective, the downside of doing the trial is that we could be wasting our time. That’s true on two scores:

·        we don’t know if Robert’s cancer will recur, and

·        we don’t know if the vaccine will work, with our without the cyclophosphamide.

Looking at the chance of recurrence, it’s higher if this was a metastatic melanoma than if it was primary – something we may never know for sure. So, we’re left with this: SIZE MATTERS, and this one was big. One estimate of the five-year survival rate for tumors larger than 4mm in resources available on the web is 37%-50%. Another website sets the five-year survival rate for Stage IIB (which includes nonulcerated tumors >4mm) at 70% and the 10-year rate at 57%. I don’t like either one ...

We will most likely seek one more opinion, this time from a melanoma expert who has no vested interest in what we decide. The easiest place to go would be the University of Pennsylvania, perhaps on our way to or from New England in the next few weeks.

If you have thoughts about any of this, please give us a call. Otherwise, we’ll keep you posted here.