What are the next steps if melanoma metastasis is found in the liver?

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AlainAlgaziMD (Physician - Oncology (Verified) ) - 09 / 24 / 2013

If you have metastatic melanoma, the first thing that I would do is take a deep breath and realize that there are more effective or promising treatment options available than every before. The next step is to try to identify which treatment options could work for you. In general, I break treatment options for metastatic melanoma into 3 categories: chemotherapy, targeted therapy, and immune therapy.

1. Chemotherapy. Chemotherapy damages the melanoma’s genes (DNA), causing melanoma cells to die, shrinking tumors and decreasing symptoms. The biggest problem with chemotherapy is that it doesn’t help people with melanoma to live longer on average. Common chemotherapy drugs used for melanoma include dacarbazine (FDA approved), temozolomide (pills that are similar to dacarbazine), and carboplatin with paclitaxel. Each has its own set of side effect and some are quite easy to take for most people.

2. Targeted therapy. Melanoma comes from normal pigment making cells in our skin that have grown out of control. This out of control growth is driven in part by broken growth switches inside melanoma cells. In a normal cell, these switches can be turn on an off as needed, but in the melanoma cell, it is as if these switches are Superglued in the on position. The growth signal is always on and the melanoma grows out of control.

The good news is that new medicines have been developed that cut the power to some of these growth switches, we just have to find out which switch is broken. Over half of patients have melanoma with a broken BRAF growth switch (BRAF mutant melanoma). In these patients, the BRAF inhibitors vemurafenib and dabrafenib (both FDA approved) can cause rapid decreases in the size of melanoma tumors and they can help melanoma patients to live longer. The major limitation is that the melanoma tumors will often start to grow again within 6 months on average, at which point patients will need another type of treatment. There is a great deal of research being done currently to try to make BRAF inhibitor work for longer. In one clinical trial, a combination of the MEK inhibitor trametinib with the BRAF inhibitor dabrafenib worked for significantly longer than dabrafenib alone. There are open clinical trials at UCSF and elsewhere looking at additional combinations to determine if these combinations can help patients who are no longer benefiting from a BRAF inhibitor to go back into remission.

Recent clinical trials suggest that BRAF inhibitors are also active against melanoma brain metastases and there are also clinical trials available for BRAF mutant melanoma patients in this difficult situation. For information on clinical trials at UCSF for patients with BRAF mutant melanoma at UCSF, feel free to contact me directly by email at alain.algazi@ucsf.edu. We also have clinical trial options for patients with another broken growth switch called NRAS.

3. Immune therapy. We have known for many years that our immune systems can fight against melanoma. Our immune systems are also fine tuned so that we don’t fight against our own normal cells. When our immune systems are overactive, we can develop autoimmune diseases such as rheumatoid arthritis and ulcerativecolitis. Ipilimumab is a drug that takes the brakes off of the immune system allowing a stronger response against the melanoma. About 11% of patients receiving ipilimumab will have their melanoma tumors decrease in size. This seems like a low number, but when these responses happen, they can last for years. Tumors will neither grow nor shrink in about 20% patients receiving ipilimumab. The average metastatic melanoma patient receiving ipilimumab will live longer than a patient who does not receive this medication. I think that the drug must be slowing down the melanoma in some patients even thought the tumors continue to grow.

There is a new generation of immune therapy drugs for melanoma in clinical trials around the country. The most promising are the PD-1 and PD-L1 antibodies. These drugs also take the brakes off of the immune response, but results thus far suggest that these drugs may have fewer side effects and a higher rate of success than ipilimumab. Clinical trials making head-to-head comparisons between ipilimumab and PD-1 antibodies are currently underway at UCSF and elsewhere.

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