A trial drug called Yervoy [ipilimumab] is looking to be a midsized step for some patients with metastatic melanoma who are not responding well to other treatments. The drug, which mobilizes the body’s own immune system to destroy tumors, is extending survival an average of four months. More than 20 percent of the patients who received Yervoy lived at least two years, and some of them much longer. 

How does Yervoy work?

Yervoy actually treats the body’s immune system rather than the cancer itself.  It improves functioning of T cells, our body’s killer cells that seek out and destroy cancer. Yervoy blocks a protein on the surface of these cells, a protein that normally inhibits T cells and acts as a brake on the immune system.

It is the third immunotherapy developed for cancer patients—the first, Proleukin, was approved for melanoma in 1998, and the second, which was recently FDA-approved, is Provenge for prostate cancer.  Provenge is a vaccine that trains the immune system to attack the cancer. Yervoy is different from Proleukin and Provenge in that it deactivates an inhibitor of the immune system rather than actually “reprogram” the immune system.

 

Treatment regimen and possible side effects

Treatment consists of four infusions over a three-month period. A small percentage of patients had severe reactions, so please ask about possible side effects, which are typically manageable if recognized and treated quickly with appropriate manuvers like steroids, according to Jeffrey Weber, M.D., Ph.D., director of the Donald A. Adam Comprehensive Melanoma Research Center at Moffitt Cancer Center.

Yervoy is covered by insurance companies in the US and some Western European countries at this time, but Bristol-Myers may offer financial assistance to certain patients who have no or limited coverage. Bristol Myers has a helpline to inquire about financial assistance.

 

The concept of using the immune system against cancer dates back to the 1890s

That’s when Dr. William Coley, a Sloan Kettering surgeon, observed that his patients who got infections after surgery often fared better. Coley theorized that the infection triggered the immune system to fight cancer.

Although vaccines or using immunotherapy against cancer is a century-old concept, researchers are generating better anti-cancer immune responses as they continue looking for them.

We have a better understanding of the molecule basis of how T cells recognize their targets. We better understand how the immune system is suppressed in cancer patients, and how to overcome that suppression,” says Dr. Weber.

“Ultimately we will have better, more effective, more directed, and less toxic immune therapies. The next five to ten years will be very productive in this area,” he says.

 

To learn about near-future Yervoy trials

Contact NCI Comprehensive Cancer Center 1-800-4-CANCER. Or visit clinicaltrials.gov  

Moving forward, researchers are looking to see which patients are most likely to benefit from Yervoy and other drugs in the pipeline.

“The idea is to define biomarkers to help us predict who will be most likely to respond to the treatment. That could be in the tumor, or in the normal host T cells,” says Dr. Weber.

  

More resources:

Treatment for Melanoma

http://www.cancer.gov/cancertopics/pdq/treatment/melanoma/HealthProfessional/page4

http://www.nytimes.com/2011/03/26/business/26drug.html

 

 

Staging and treating melanoma

Once a melanoma is staged, the best treatment plan can be determined; and there are several options.

Stage 0 melanoma

Most early melanomas can be staged solely with a biopsy. It’s a quick, simple procedure done in the doctor’s office. For Stage 0, which is when the cancer is only in the outermost layer of skin (epidermis), the tumor is removed, and you are done other than needing to monitor yourself. There is close to 100 percent cure rate.

 

Stage 1 melanoma

The tumor is no bigger than 2 ml. It is confined to the middle layers of skin (dermis) and sometimes the subcutis.

The sentinel lymph nodes (nearest the tumor) may be biopsied, though chances are they will be cancer-free. While no more treatment may be necessary, adjuvant therapy (treatment after surgery) may be an option for at least Stage 1B. Adjuvant therapy, typically done in clinical trials, may involve lymph node removal. It may involve immunotherapy, where the body’s own immune system fights the cancer; it may involve chemotherapy. Or a combination of the later two treatments.

 

Stage II melanoma

The tumor is at least 1.01 ml and lymph nodes are clear of cancer. The lesion may be intact, or ulcerated (not in tact). This means the epidermis overlying the melanoma is missing.

You may have imaging tests to learn more; these could include chest x-ray, MRI, CT scan and or PET scan.

“Imaging studies can be very helpful.  My preference is the PET/CT scan which fuses PET scan images (metabolic imaging - cancerous tissue takes up more of the radioactive glucose than normal tissue) with CT images (anatomic imaging – showing abnormal location or abnormal size of tissue,” says Dr. Peter Beitsch, an oncology surgeon in Dallas, Tx. 

Treatment may entail removing any tumor that may be left after the biopsy, and with stage IIC, interferon injections (immunotherapy) may be an option. Some trials have shown higher relapse-free and overall survival rates with interferon.

“There have been many studies to determine if alpha interferon is beneficial as an adjuvant treatment (after standard surgery),” says Dr. Beitsch.

“There is no clear cut answer, but the preponderance of evidence shows that interferon prolongs disease-free survival and probably overall survival.  No other drugs have shown improved survival in Stage 1-3 melanoma patients.  However, the new drugs that improve survival in Stage 4 melanoma patients are now being studied in Stage 2 and 3. So hopefully we will find we have more effective therapies for these patients, ” says Dr. Beitsch.

If you are considering an experimental drug talk to your doctor about possible side effects, how you will be monitored, and to ensure a back up plan if needed.

 

Stage III melanoma

This melanoma has spread to the lymph nodes. Your doctor will learn more about the cancer and ultimately how to treat it by ordering chest x-ray, MRI, CT scan, and or PET scan.

Treatment is surgery to remove the tumor and nearby lymph nodes. Chemotherapy and sometimes immunotherapy (typically interferon injections) and or a combination of these drugs are options available in clinical trials.

If the tumor is isolated to an arm or leg, high-dose chemotherapy, administered to the affected limb may effectively destroy the cancerous cells while sparing healthy ones. Radiation may be used when there are multiple lesions.

 

 Stage IV melanoma

This cancer has spread beyond the lymph nodes. The first plan of action is to biopsy areas where the spread is suspected. Your doctor may order a chest x-ray, and/or other imaging tests.

While surgery may not reach all the cancer there are options to manage it. One may be chemotherapy; an FDA-approved drug is dacarbazine (DTIC), often used with other drugs like temozolomide to bolster its effects. Immunotherapy in the form of interluekin-2 (IL-2) or interferon alpha injections may be possibilities. 

The options are expanding.

In 2011, two drugs were approved for metastatic patients – Yervoy (anti-CD4 antibody that relieves immunosuppression) and Zelboraf (BRAF inhibitor that kills melanoma cells directly. 

Ongoing studies combine these two as well as drugs used in the past to see if combinations will bolster effectiveness.  In addition, there are several vaccine trials. And there are new targeted therapies (against NRAS and MEK gene mutations for example) that hold promise, according to Dr. Beitsch.

Meanwhile, some advanced patients opt for palliative care, which solely manages symptoms, to improve quality of life. Radiation is one palliative approach for comfort level. 

Moving forward, please make sure you are comfortable with your doctor, treatment plan, and if you would like more resources, here are a few good ones:

 

Staging and treating melanoma

http://www.skincarephysicians.com/skincancernet/melanoma_staged_treated.html:

New immunotherapy for advanced melanoma

http://www.reuters.com/article/2012/06/02/us-cancer-bristol-immunotherapy-idUSBRE85102O20120602

Melanoma clinical trials

http://bethesdatrials.cancer.gov/melanoma/index.aspx?gclid=CITJgtnjr7ACFYd9Ogodb1F5TA

 

 

 

Combination therapies for late stage melanoma

Hoping to improve outcomes in patients with metastatic melanoma, researchers are combining chemotherapy regimens. There is plenty in the pipeline, with IL-2 often one of the players in these combination therapies. IL-2 is an immunotherapy that creates killer cells and tumor-infiltrating cells.

One landmark study
Pub Med reports on 16 patients with melanoma who were considered high risk for recurrence. After surgery they received GM-CSF, a drug that earlier studies found provides an anti tumor effect that prolongs both disease-free survival and overall survival in patients with stage III and IV melanoma. GM-CSF was followed by IL-2, and patients with large tumors received autologous melanoma vaccines as well. At 21 to 42 months follow up, 11 of the 16 survivors had no metastases. The treatment brought on minimal side effects and was done on an outpatient basis.

The report concludes: “The combination treatment regimen of GM-CSF and IL-2 with or without autologous vaccine used adjuvantly appears to benefit high-risk melanoma patients; further clinical testing is warranted.”  However, the study was published in 2005, with no published follow ups to date. But moving forward, there have been over a hundred studies on combined therapies for advanced melanoma. For instance sorafenib with paclitaxel and carboplatin versus paclitaxel and carboplatin with placebo.

A new combination therapy
Some oncologists are beginning to offer treatment options, independent of clinical trials, using two new FDA-approved drugs with IL2, hoping to boost the number of positive responses in patients with advanced melanoma, according to  Valerie Guild, president of AIM at Melanoma.

The new therapies are  Yervoy (ipilimumab)  and Zelboraf (vemurafenib). Yervoy is a form of immunotherapy that has extended survival time in recent clinical trials. Zelboraf is a kinase inhibitor that has shown promising results in survivors with the BRAF mutation.

“These are approved drugs and it is up to the doctor to determine if he or she wants to try this regimen,” says Valerie.

Yervoy and Zelboraf, like many treatments for melanoma are very aggressive to hopefully get the best outcomes. This means they may have intense side effects that you should discuss with your doctor before deciding on your treatment plan.

“We don’t yet know what the results will be with some of these combination therapies. But this approach of seeing how they work together is where we are now. And it’s where the science is going,”  says Valerie.

The topic of combination therapies for advanced melanoma is on the agenda for an upcoming AIM conference, open to the public.

Related information:

NCI Melanoma page
http://www.cancer.gov/cancertopics/types/melanoma

Sorafenib with paclitaxel and carboplatin
http://www.cancer.gov/cancertopics/types/melanoma

GM-CSF and IL-2
http://www.ncbi.nlm.nih.gov/pubmed/15934495

Yervoy
http://www.nytimes.com/2011/03/26/business/26drug.html

Zelboraf
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm268241.htm

 

 

Forging ahead on targeted therapies

More information:

Below is  an article from WebMD.  Since it’s writing, researchers have further investigated possibilities in vaccines for fighting melanoma. They continue to look closer at more than a dozen innovative approaches with just a couple being using individuals’ own tumors or mass producing other patients’ tumors. The cancerous cells are used to teach the immune system to identify and attack melanoma.

 

 Vaccine for melanoma

By Charlene Laino (WebMD)
June 1, 2009 (Orlando) — For the first time, a vaccine that trains the immune system to seek out and attack cancer cells has been shown to shrink tumors in people with melanoma.

In a study of 185 melanoma patients, the experimental vaccine also extended the time that people remained free of cancer.

There are even indications that people given the vaccine live longer, but patients need to be followed longer before researchers can be sure, says Patrick Hwu, MD, head of melanoma medical oncology at the University of Texas M.D. Anderson Cancer Center in Houston.

Hwu presented the results at the annual meeting of the American Society of Clinical Oncology.

How it works

Unlike the vaccine that helps prevent cervical in healthy women, the melanoma vaccine is designed to help people who already have cancer.

The vaccine is given along with interleukin-2, or IL-2, the standard treatment for melanoma. IL-2 stimulates the immune system to attack and kill cancer cells. Tumors shrink in one in four patients with advanced melanoma who get this treatment.

The vaccine contains a substance, called gp100, that is on the surface of melanoma cells. The idea is that the immune system will see this as a threat and incite an even stronger attack against cancer cells.

“The vaccine is capable of taking immune system soldiers to boot camp. Then, interleukin-2 multiplies them into an army,” Hwu tells WebMD.

In the study, people with advanced melanoma were given the vaccine or a placebo injection, followed by four days of intravenous interleukin-2 treatment. This was repeated every three weeks until the tumor shrank or the cancer progressed.

Tumors shrank in 22% of patients given the vaccine plus interleukin-2, compared with 10% of those given interleukin-2 alone. The experimental treatment also extended the time until the cancer started growing, from about one-and-a-half months for interleukin-2 alone to nearly three months for the one-two punch.

That may not sound like much, but cancer advances are made in baby steps, says Len Lichtenfeld, MD, deputy medical director of the American Cancer Society.

Lichtenfeld tells WebMD that there’s reason for “cautious optimism.” A lot of cancer vaccines that seemed promising in early studies haven’t panned out, he says.

Louis M. Weiner, MD, head of the Lombardi Comprehensive Cancer Center in Washington, D.C., says the vaccine study is the latest in a series showing that the immune system can be mobilized to attack cancer.

“Many of us believe that a combined approach that includes an immune system attack on cancer cells will ultimately prove to be most useful in controlling cancers such as melanoma,” he tells WebMD.

Hwu says the next step is to try to reproduce the findings in a longer, larger study. Also, his team hopes to add yet another punch — in the form of an agent that takes the brakes off the immune system.

Then, the immune system soldiers can proliferate with impunity, hopefully killing even more cancer cells, he explains.

SOURCES:
American Society of Clinical Oncology Annual Meeting 2009, Orlando, May 29-June 2, 2009.
Patrick Hwu, MD, head of melanoma medical oncology, University of Texas M.D. Anderson Cancer Center, Houston.
Len Lichtenfeld, MD, deputy medical director, American Cancer Society.
Louis M. Weiner, MD, head of Lombardi Comprehensive Cancer Center, Washington, D.C.

 

 

Progress in advanced melanoma

A new drug extends progression-free survival in half of advanced melanoma cases. PLX4032 blocks the mutated BRAF gene, a gene that triggers some cancers. The mutation is found in up to 60% of melanoma patients.  The therapy is in a pill and found in trials to work even in people no longer responding to standard treatments (New England Journal of Medicine Aug. 26).

What the studies show …

81% of patients in the study, done at Massachusetts General Hospital, responded to treatment. Duration of response ranged from two to over 18 months

What next …

A larger trial is now in progress on PLX4032. While the trial continues a similar drug called GSK2118436, is being investigated. While these targeted therapies are a step forward, researchers anticipate patients will eventually build resistance to them and are already focusing on overcoming the challenge by looking at combining PLX4032 with other drugs.

For more information:

www.nature.com/news/2010/100907/full/467140b.html

To learn about clinical trials:

www.clinicaltrials.gov/ct2/search/browse?brwse=cond_cat_BC04

Itself in

 

Human antibody added to mix in advanced melanoma

A therapy that boosts the body’s immune system has extended the lives of patients with metastatic melanoma – the first medical breakthrough for this disease in decades. The study enlisting 125 centers was recently reported in New England Journal of Medicine.

Patients who received ipilimumab survived for an average of 10 months whether they received the drug alone or in combination with a vaccine known as gp100.   This extended their lives by an average of four months over patients who received gp100 alone. Ipilimumab was also more effective at controlling the disease: after six months, there was no progression in nearly 30 percent of those receiving ipilimumab, compared to 11 percent with the vaccine.

Ipilimumab represents a new class of human antibodies that activate the immune system, which finds and destroys cancerous cells. Patients who responded to the drug were found to have a genetic mutation disabling the immune response. Researchers believe the science is moving in the right direction with a very difficult disease in patients who had become resistant to therapy. They are now looking to combine this class of therapies with other treatments, hoping to continue to improve outcomes.

Do not give up when you hear the numbers. Here’s a blog I found:

I was first diagnosed with metastatic melanoma in 2006 at M. D. Anderson Cancer Research Hospital, Houston, Texas and underwent successful surgery. I took Interferon prophylacticly for six months after surgery. Two months after I voluntarily discontinued the Interferon the melanoma returned. I received 9 doses of IL-2 which did more to kill me than to kill the cancer. It was discontinued by my cancer team. I was offered Ipilimumab and took the four infusion protocol. It killed the cancer!”No evidence of the disease in your body.”

In April 2010 melanoma was found in a nearby lymph node after testing. Surgery tomorrow, June 7, 2010 will remove the cancerous lymph node. I recognize that the results I got from ipilimumab are not typical of all patients in all clinical trials around the country. However, if I could advise the FDA, I would say, “We need ipilimumab approved ASAP!” It works! At least it did for me.”

For more information

www.ecancermedicalscience.com/news-insider-news.asp?itemId=1069

 

 

Below is  an article from WebMD.  Since it’s writing, researchers have further investigated possibilities in vaccines for fighting melanoma. They continue to look closer at more than a dozen innovative approaches with just a couple being using individuals’ own tumors or mass producing other patients’ tumors. The cancerous cells are used to teach the immune system to identify and attack melanoma. Experimental Vaccine Shrinks Deadly Skin Cancer

reprinted from WebMD Health News

 

From WebMD – -

(For those of you who did not see Season 1. This is Kimberly Bryant who moved out of SoCal after season one due to cancer scares. Following is an interview she did prior to leaving)

Reality T.V. Star Becomes Melanoma Patient

TV star Kimberly Bryant’s wake-up call came when her doctor found and removed a malignant mole.
Orange County, you faced a serious health threat. What happened?

My doctor found a malignant mole — a shallow melanoma in early stages — on my thigh, a few inches above my knee. I’ve faced skin cancer before, but I never intended to share this “reality” on the show. Now, I’m glad I did. Since the show has aired, several people have told me they’ve gotten their skin checked because of me — and it thrills me to hear it.

When were you first diagnosed with skin cancer?

At age 27 — 17 years ago. I went in for acne treatments and my doctor gasped. He removed 22 moles from my body. He tested them all, and one came back malignant.

Were you a sun worshipper when you were young?

I got a tremendous amount of sun exposure as a child. All the damage was done before I was 25.

You write on your Bravo blog that you had an eye sewn shut for two months after half of your lower eyelid was removed due to skin cancer. Tell us about this experience.

I had a tiny tumor near my tear duct. It was not malignant, but I still tell everyone: Wear sunglasses! Make sure your children wear sunglasses! Protect your eyes!

How much has changed in the last two decades, in terms of prevention and treatment of skin cancers?

Not enough. It will take someone like Brad Pitt getting melanoma to get the kind of funding needed to get the research done that this cancer needs.

Any advice for other mothers trying to keep their families safe from UV rays?

When my kids were little, it wasn’t hard keeping them covered up. Now they want to be at the beach with their friends — and not look dorky in long sleeves. But there are companies that make cute clothes that have sunscreen built into the fabrics. Also, be creative. Don’t tell your teenager she can’t go to the beach. Instead, plan an indoor activity for her and her friends — like going to a cool sushi bar or a museum — then take them to the beach after 4 p.m. Watch the sunset together.

Since facing cancer, do you view your life or relationships differently?

Completely. Yes, plan for the future. But enjoy the moment. Share your feelings for someone right now. Take more risks. Have a sense of adventure.

How do you feel about aging?

I like it. I am more confident in my 40s than I was in my 20s. I’ve got a great husband, great kids; I’m more direct. And physically? Well, I do look at my skin and wish I didn’t get so much sun.