At a news conference on April 7, a Sylvester Comprehensive Cancer Center patient talked about his participation in a clinical trial that explored the role of a well-known erectile dysfunction drug in weakening head and neck squamous cell tumors prior to their surgical removal.
The patient, Marc Giattini, had most of his tongue removed and then rebuilt using a skin flap from his left forearm. He spoke clearly and eloquently of his illness, his recovery and his participation in the trial, which used the erectile dysfunction drug Tadalafil, known to consumers as Cialis, to promote his immune systems response against his tumor.
For Giattini, 62, an attorney who lives on Sanibel Island, his 2013 diagnosis began his second bout with head and neck squamous cell carcinoma, a deadly disease that has a high rate of recurrence 50 to 60 percent if initially presented at an advanced stage despite improvements in treatment. An earlier cancer had been treated in 2004.
You have to imagine how surreal it was to be sitting in a meeting with a doctor who was telling me that my cancer had returned, and he wanted to cut my tongue out of my head and replace it with part of my arm,said an animated Giattini, drawing laughter from the audience. Then he told me he also wanted to test an erectile dysfunction drug on me something I dont even need. Initially, I didnt like the idea at all.
But hisENTback home, who referred him to Sylvester, convinced him to take part in the trial. It didnt take long for Giattini to notice an effect.
Prior to the surgery, I was in a lot of pain and had trouble eating, he said. “After about 10 days taking Cialis, however, I could absolutely feel the tumor reduce in size. The monster in my mouth was getting smaller.
The surgeon to whom Giattini was referred, Donald T. Weed, M.D., professor of otolaryngology and Sylvesters Head and Neck Site Disease Group Leader, also spoke at the news conference, as did researcher Paolo Serafini, Ph.D., assistant professor of microbiology and immunology and otolaryngology, whose finding in the laboratory led to the Tadalafil clinical trial.
“We certainly didn’t expect Tadalafil to shrink the tumor,” said Weed, “and if it did shrink slightly, it didn’t affect how we performed the surgery. It was really about the drug’s effect on the cancer cells, which is much more subtle and hopefully has longer-term benefits.”
Prior research at the Miller School and other institutions had identified myeloid derived suppressor cells (MDSCs) and regulatory T cells (Treg) as important components in the cancer cells’ defense against attack by the immune system. Preclinical studies with mice had also shown that Phosphodiesterase-5 inhibitors could suppress MDSCs and Treg by modifying the tumor environment.
“Those inhibitors are found in Tadalafil and similar drugs that already have FDA approval for humans, so we were able to proceed directly to a clinical trial,” said Serafini. “Our goal was to see if we could interrupt the molecular and cellular mechanisms by which tumor cells can block the immune system.”
That goal was achieved with Giattini and other participants who took a moderate dose of Tadalafil for three weeks prior to their surgery. The researchers also found that Tadalafil increased the presence of CD8+T cells, which boost immunity against squamous cells and minimize tumor growth.
“This was a proof-of-principle trial,” said Weed. “Now we are designing a second trial, which will begin in about three months, for patients with advanced-stage cancer that has recurred after previous treatment, particularly after radiation. We will give those patients Tadalafil in combination with a tumor vaccine. Instead of just trying to block the cancer cells, we will combine surgery with an immunologic treatment designed to reduce the immune-suppressive characteristics of the cancer cells and at the same time rev up the immune system attack against the cancer cells.
“After their surgery, those patients will continue to receive Tadalafil combined with the vaccine — a sort of ‘booster’ vaccine — over the course of a year. The goal of that trial is to achieve improved survival of the patients.”
Giattini, meanwhile, is now cancer-free, and he and his wife, Cheryl, who was also at the news conference, were all smiles. Still, it hasn’t been easy. Giattini has undergone extensive rehabilitation therapy, relearning how to speak, eat, swallow and perform many other mouth-related functions that most people take for granted. Yet there he was, having long conversations with reporters, his speech sounding virtually normal. His wife reports that he even retained all of his taste buds.
“It’s miraculous,” she said, “and we’re so grateful that a wonderful place like Sylvester is available to us. After Marc’s doctor referred him to Dr. Weed, we called late on a Friday, and Dr. Weed saw us first thing Monday morning. You never expect treatment like that, but Sylvester is special.”