• 3/8/2002
  • Havana, Cuba
  • Mary Murray
  • Nbc News

Cuban researchers this week reported early, but notable success with a biotech drug that attacks advanced cancer of the head and neck regions. In preliminary trials, the novel agent, called Theracim h-R3, enhanced conventional radiation therapy to radically shrink and even completely eradicate tumors.

Researchers at Havana’s Center of Molecular Immunology administered radiation plus Theracim h-R3 to 70 patients whose head and neck cancers had failed to respond to conventional therapy. Tumors completely disappeared in 60 percent. In contrast, only 30 percent to 40 percent of advanced patients given radiation alone in Cuba would expect to see their tumors eliminated, said the Center’s Normando Iznaga-Escobar. To date, patients given the one-two punch from radiation and Theracim h-R3 have remained tumor-free for as many as 28 months, he added. Additionally, another 20 percent of patients saw their tumors shrink by at least half, said Dr. Rolando Perez, head of the Center’s research and development division. “Few therapies have demonstrated such an overall response rate and survival benefit of this disease,” said study author Dr. Tania Crombet, also of the Center.

To develop Theracim h-R3, the researchers took advantage of the fact that the growth of some tumors is fueled by substances known as epidermal growth factors. And, on their outside shell, some tumors have chemical docking stations known as receptors to these growth factors. Scientists figured out that when they stimulate these receptors, tumors grow faster than ever. So, they reasoned that if they developed an antibody that seeks out, attaches to and gums up these receptors, cancer growth will be slowed, even halted. Which is just what happened, according to Iznaga-Escobar.

HER-1 TARGETED
Specifically, Theracim h-R3 inhibits an epidermal growth factor receptor known as HER-1. Up to 90 percent of patients with head and neck cancer have too much HER-1, he said, causing cancer cells to reproduce out of control and spread through the body. Dr. Roy Herbst, a molecular oncologist at M.D. Anderson Cancer Center in Houston, said that HER-1 “is a good target” for an anti-cancer drug. By blocking HER-1, which has been implicated in head and neck, colon, pancreatic and other tumors, a drug should theoretically slow down, even reverse, cancer’s course. But large clinical trials comparing the drug to placebo are needed to prove that, Herbst said. In the United States, where radiation therapy is more sophisticated than in Cuba, the tumor-eradication rate can reach 60 percent – as high as seen in the Cuban trial of radiation plus Theracim h-R3, he added. And other HER-1 blockers, such as IMC-C225, are further along down this road than Theracim h-R3. “This is interesting, but for now it’s just another of many such molecules being tested,” Herbst said. “We look forward to seeing further study.”

A head-to-head trial comparing radiation plus placebo to radiation plus Theracim h-R3 is already underway by the Center, in partnership with Ontario-based YM BioSciences Inc., said Iznaga-Escobar. He acknowledged that there are some other agents further along in development. But, he added, Theracim h-R5 has a very favorable safety profle, the most common side effects being mild fever, chills and nausea in some 45 percent of patients.

FAST TRACK
According to Perez, Cuba’s National Regulatory Authority – the U.S. Food and Drug Administration’s equivalent – has placed Theracim h-R3 on fast-track approval. In Cuba, unlike in the United States, this allows the drug to be sold during the final phase of testing now underway. That makes Theracim h-R3 one of only a handful of so-called humanized monoclonal antibodies available around the world, he said. Others include Panorex, approved in Germany in 1994 for patients with colon cancer, and Herceptin, approved in the United States for treating breast cancer. If the final phase of testing goes as expected, with the same good results, Perez said he believes Canada will approve Theracim h-R3 by early next year.

HEAD AND NECK CANCER
In 2001, close to half a million new cases of head and neck cancer were detected around the world. During that same period, 244,413 people died from the disease. Cuba’s National Cancer Institute blames lifestyle, particularly alcohol abuse and tobacco consumption, as the leading causes. “Cuba has the dubious distinction of having one of the highest smoking rates in the world. We are in the midst of a very important anti-smoking campaign. If we manage to reduce smoking over the next 20 years, we could cut all cancer rates by one-third,” said CNCI’s Dr. Miguel Azcuy.

Portia Siegelbaum in Havana contributed to this report.