May 5, 2011

VICC patients show benefit from new melanoma drug

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Jeffrey Sosman, M.D., examines patient Marcia Akers, who is enrolled in a clinical trial for a new melanoma drug. (Photo by Susan Urmy)

VICC patients show benefit from new melanoma drug

On Mother’s Day 2008, Marcia Akers was expecting a traditional Mother’s Day gift from her children. Instead, she received a piercing pain, like a lightning bolt streaking down the right side of her body. The seizure resulted in a trip to a Nashville hospital where tests revealed a golf ball-size tumor in her brain. Doctors told her it was probably cancer.

Akers’ physicians ordered stereotactic radiation to shrink the tumor but her seizures continued. A friend finally referred her to Vanderbilt University Medical Center’s Reid Thompson, M.D., William F. Meacham Professor and Chairman of Neurological Surgery, who performed surgery to remove the tumor and ordered additional tests on the tumor tissue.

Those tests showed Akers had melanoma, the most deadly form of skin cancer.

“I was very healthy, riding horses and out in the garden, but I was not a classic sun worshipper,” Akers explained. “I didn’t have it on the outside of my body that they could find.”

Thompson knew that Jeffrey Sosman, M.D., professor of Medicine, and leader of Vanderbilt-Ingram Cancer Center’s (VICC) Melanoma Program, is helping guide international clinical trials of innovative drugs to treat melanoma.

Sosman ordered an MRI and PET scan to determine the extent of Akers’ disease, but the scans were not encouraging. The melanoma was very advanced, involving her brain, liver, lung and bone. Sosman was reluctant to tell Marcia and her husband, Andy, the rest of the story – many patients with stage IV disease live only a few months after diagnosis.

Akers struggles to hold back tears when she remembers that point in her life.

“I set about putting my affairs in order. I was through with the land of the living and was trying to figure out the best way to die and to leave my family and my friends and leave them with something good,” Akers said.

But within a few weeks, Sosman enrolled Akers in a clinical trial for the drug ipilimumab, which works by triggering the patient’s own immune system. VICC is one of the cancer centers participating in advanced trials for the drug.

Ipilimumab (Ipi) is a targeted antibody directed against an antigen on the surface of T-cells (a type of immune cell). The antigen, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), acts as a brake on the T cell. Ipilimumab lifts this brake, allowing the T cells to go into attack mode and kill cancer cells.

“When you lift this brake on the immune system, you can get a profound effect,” Sosman explained.

Akers was among the nearly 10 percent of VICC patients whose melanoma responds immediately to the drug, given as an infusion every few weeks.

“For many, it can take awhile for the Ipi to manifest its positive effects, so it likely does not work in patients whose disease is rapidly progressing,” said Sosman.

This new class of drug is a double-edged sword because it can activate the immune system to attack the patient’s healthy cells.

Patients who get an immune backlash can experience colon inflammation, colitis with diarrhea, hepatitis, endocrine deficiencies and rash.

Marcia Akers’ only side effect is a small rash and after two years on the drug, her tumors have shrunk dramatically and the cancer is not active.

Even though ipilimumab does not cure melanoma, Sosman believes the drug trials have moved the research curve forward. The Food and Drug Administration recently approved ipilimumab for use in melanoma patients with metastatic disease.

“We see a 60 percent benefit in the duration of survival for these patients, and I think this and other new drugs put an end to the use of chemotherapy alone as first-line therapy for melanoma,” Sosman said.

Marcia Akers is pleased that a clinical trial at Vanderbilt gave her a second chance.

"I was dying with cancer and now I'm living with cancer. That's a hopeful place to live,” Akers said with a smile.