For me, moving on from Robert’s active fight against melanoma Stage IIB into the nerve-wracking “watchful waiting” phase means keeping up-to-date on the latest research into therapies in use or under study for patients with more advanced disease. I’ll share some of what I’ve learned so far, and then I’ll try to keep you informed when I learn something new.

To understand how researchers are trying to fight melanoma, first you need to understand what cancer is. I’ll start with a short primer; click here to jump to the next section if you want to skip it.

Cancer Primer

You may already know that cancer is a condition caused when abnormal cells reproduce like crazy. In leukemia and lymphoma, this floods the blood or lymphatic system with abnormal cells. In other cancers, it causes tumors that not only grow in place but also have the capability to shed cells that travel to other parts of the body and grow a new tumor – the dreaded metastases. Although these tumors grow in a different part of the body from where they started, they still have the characteristics of the original tumor. In other words, a metastatic melanoma tumor growing in the lungs or brain (or wherever) has all the characteristics of melanoma – it’s just growing in another part of the body.

Also note the difference between “malignant” and “metastatic.” Malignant tumors have the capability to metastasize, but they don’t all do that. For example, some cancers are caught early enough to be eliminated before they actually send any tiny metastases out into the rest of the body. This includes the “melanomas in situ” that are Stage 0 or 1 (depending on size, depth, and whether they have ruptured or “ulcerated.”)

The question I keep asking is why the body’s immune system doesn’t attack these abnormal cells the way it does other foreign cells or bodies that don’t belong there. That’s also the question researchers are asking ... and so far they don’t know the whole answer. What they do know is that cancer cells activate proteins that effectively turn the immune system off to the cancer cells. While a cancer patient’s immune system might continue to fight infection, it either ignores or doesn’t recognize the cancer cells.

This is a pretty sketchy primer. If you want more details, one place to start is the National Cancer Institute’s What is Cancer page. If that’s too technical for you, try the What is Cancer page on the American Cancer Society’s website.

Melanoma Therapies

Therapies used to fight melanoma are of three types:

• chemical and/or biological agents designed to kill active cancer cells,
• immunotherapies that stimulate the body’s built-in immune system to fight the cancer on its own, and
• vaccines that target melanoma cells so that the body’s immune system will recognize and fight them.

According to the American Cancer Society, standard cancer treatments such as chemotherapy are not very effective against melanoma even though they are very toxic. Therefore, most melanoma therapies in use and under study today are immunotherapies or experimental vaccines.

The toxic side effects of chemotherapy drugs are the reason one physician we consulted cautioned us against agreeing to enroll in a clinical trial that has some study participants take cyclophosphamide. Researchers want to know if taking the chemo drug first to knock out lymphocytes that interfere with the immune response the vaccine is intended to create improves the vaccine’s efficacy. We weren’t faced with the decision about whether it’s worth the risk, however, because Robert was placed in a phase of the study that’s testing the GVAX melanoma vaccine without the nasty stuff.

The main melanoma treatments that have been approved so far are immunotherapies. Manufactured versions of the immune-boosting molecules interleukin-2 (IL-2) and interferon-α are used primarily against advanced disease, sometimes in combination with chemotherapy drugs. Whether used alone or in a biochemotherapy mixture, they can have severe side effects and often don’t prolong the patient’s life by more than a few months. About 10% to 20% of Stage III and IV patients treated with these therapies see their tumors shrink. Those odds aren’t very good, and given the bad side effects, these therapies aren’t generally used against Stage 1 or Stage 2 disease.

The newest immunotherapy approved to treat melanoma is ipilimumab, marketed by Bristol Myers Squibb as Yervoy® and known in the melanoma community as “ipi.” Ipi works by blocking the protein CTLA-4, which inhibits the immune system from attacking the melanoma cells. It has been shown to extend the lives of some patients with advanced disease, but it also causes severe gastrointestinal side effects in some patients.

All of these approved treatments are good at one thing: buying time for patients whose melanoma has advanced to Stage III (local or regional spread) or Stage 4 (metastatic melanoma, spread to other parts of the body). The real promise lies further in the future, with treatments designed to destroy the tumors themselves. I’ll write more about some of that research when I can figure out what it’s all about.

For now, I’ll turn my mind to the weekend, which has great promise: a lovely weather forecast, and a visit from my friend Sue. Then, next week, we go to Hopkins for the last visit of the clinical trial, including six-month scans. I’ll let you know the results as soon as I get them.