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Melanoma Treatment: Stage IV

Stage 4 melanoma, although the most life threatening, offers the most treatment options. Whereas, stage 1 and 2 are cured by simple outpatient surgery, and stage 3 has few adjuvant therapies is watched similarly, stage four treatments are being studied in many clinical trials.  

Old Therapies
Although chemotherapy in very few instances produces dramatic regression of disseminated melanoma, it only rarely results in long-term survival. Indeed, in a recent review of chemotherapy for cancer in advanced stages, melanoma patients were classed with those who could expect only "minor response—no demonstrable prolongation of survival" from chemotherapy. Another option that is an older therapy includes immunological hormones called cytokines, such as IL2 also called Interleukin.  In a few patients, disease may actually melt away and have a sustained response. But the rate of response is in less than 10% of patients with much associated toxicity.  The role of IL2 intermixed with Ipilimumab and other therapies may hold promise in the future although that remains unproven.

NEW Therapies
Anti-PD1 and other Monoclonal Antibodies
New therapies that stimulate the immune system to respond to melanoma may offer effective therapy in the future. For example, anti-CTLA 4, or Ipilimumab (Ipi), now approved by the FDA, is a human monoclonal antibody which targets certain cells in the body by attaching themselves to those molecules. This causes some cancer cells to die and makes others more likely to be killed by other therapies. Ipilimumab  blocks a protein called CTLA-4 that acts as a brake on T cells, the soldiers of the immune system. Ipi is administered intravenously (3mg/kg) over 90 minutes every 3 weeks for a total of four doses.  Response can be slow but also durable.  Approximately 15 to 20% of melanoma patients respond to this therapy. A molecule akin to Ipi, both still early in clinical trial but is said to be highly promising and less toxic than Ipi.  Currently, PD1 is in phase three trials.
 
New Targeted Therapies for Melanoma:  BRAF and MEK
When you are diagnosed with melanoma your oncologist may bring up the term BRAF or MEK with you.  And Plx 4032, or Vemurafenib a BRAF inhibitor was approved for prescription by the FDA  in the fall of 2011.  Approximately, 50% of melanoma patients tumor tissue tests positive for this genetic mutation.  A mutated BRAF accelerates tumor cell growth and this change can increase the growth and spread of cancer cells. Therefore, these BRAF drugs target the cancer-causing mutation in melanoma.  The BRAF oral medication should not be given to those without the mutation as it could actually accelerate tumor progression. BRAF mutations usually arise from sun exposed skin and rarely from those melanomas such as mucosal, ocular or acral whose origin is not clearly known yet.In order for these therapies to work most effectively, you need first  to be BRAF positive.Your tumor tissue must test positive for the BRAF gene before you can be prescribed this oral agent.  MEK on the other hand is a bit different with less information available on its performance.  It does appear that you can be Braf Negative and respond to the MEK drugs. BRAF and MEK have been combined in clinical trial showing promising results with more durability than Vemurafenib and may be approved soon by the FDA.

There are many clinical trials to explore, with new therapies arising every day.  Contact our helpline, 866-463-6663 or email cpoole@melanomainternational.org, to find help matching you to a treatment trial if that is what you choose to do.  Also be sure to look at the ongoing discussions of current therapies at www.melanomaforum.org .  You can also go to:  www.clinicaltrials.gov  and put melanoma in the search for a list of trials.

SOURCE:

2010 ASCO Proceedings published by Cancer Care
BRAF article edited by Keith Flaherty, MD  Dir. of Therapeutics at Mass General Hospital

 UPDATE: February 12, 2013


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