A Ray Of Hope For Cancer Patients
Six years ago, Melvin A. Francis' doctors broke the bad news that he had cancer of the esophagus. A gruesome disease that strikes 12,000 Americans each year, the cancer leaves many of its victims unable to swallow, and for 95% of them, results in death. Francis, then president of a thriving Tennessee manufacturing company, was appalled at the surgical prospects described by Dr. Bergein F. Overholt, his gastroenterologist at Knoxville's Thompson Cancer Survival Center. Much of his esophagus would have to be removed in an operation so mutilating that he would probably never eat normally again.
Fortunately, there was an alternative. At Overholt's suggestion, Francis became one of the first Americans to undergo an experimental procedure called photodynamic therapy (PDT). First, Overholt injected Francis with Photofrin, a photosensitive drug that accumulates in cancerous cells (table). Three days later, he exposed the tumor to a low-power red laser light for 30 minutes. This triggered a reaction that killed the cancer cells without burning surrounding skin. "It was a cakewalk," says Overholt, who sent Francis home the same afternoon. Francis, 67, is now cancer-free. And the treatment eased his chronic heartburn as well. "I can eat chili, or anything else I want," he brags.
It may sound like a miracle cure, but Francis' recovery was no fluke. Bolstered by similar, dramatic results from trials in Japan, Europe, and North America, PDT is emerging as one of the most promising new therapies in medicine. Last December, the Food & Drug Administration approved Photofrin for use in advanced esophageal cancer. In late April, Japan's national health insurance plan agreed to cover Photofrin as a potential cure for early-stage cancers of the lung, esophagus, stomach, and cervix. France, Canada, and the Netherlands have recently approved it for more limited uses against cancer. "There's going to be an explosion of interest as new [PDT] drugs are developed," predicts Dr. Harvey I. Pass, head of the thoracic oncology section at the National Cancer Institute in Bethesda, Md.
PDT, however, is more than a cancer treatment. Because the photosensitive drugs it employs accumulate in any rapidly growing cells, not just cancerous ones, researchers say it can be used with many disorders, from psoriasis to degenerative eye diseases. Dr. D. Geoffrey Shulman, chief executive of New Jersey-based Dusa Pharmaceuticals Inc., one of several small companies developing PDT drugs, anticipates a multibillion-dollar annual market in the next 5 to 10 years. In recent months, pharmaceutical giants Ciba-Geigy, Pharmacia & Upjohn, and Sanofi Winthrop have signed alliances with PDT drug developers.
All this has sent PDT stocks soaring. Despite some recent profit-taking, drug developer PDT Inc. of Santa Barbara, Calif., boasts a market capitalization of some $500 million, up from $65 million after its initial public offering in April, 1995. Industry leader QLT PhotoTherapeutics Inc., of Vancouver, maker of Photofrin, is trading near 23 on NASDAQ, five times its 52-week low. Given the therapy's huge potential, all PDT-related stocks will likely appreciate further in coming months, predicts Jeffrey H. Berg, an analyst at H.H. Meyerson & Co. in Jersey City, N.J.
BLOCKBUSTER. Skeptics contend that this extraordinary runup is excessive. "PDT may take longer to pay off than investors realize," cautions Ezra Lwowski, an analyst at Toronto-based Yorkton Securities Inc.
Most medical people who are familiar with PDT, however, seem convinced it will be a blockbuster--partly because it fits so well with the cost-conscious medical climate. For one thing, PDT is less invasive than conventional surgery. The current recommendation for lung cancer, for example, is surgical removal of all or part of the lung, requiring 5 to 10 days in the hospital. Patients treated with PDT rarely require hospitalization.
In addition, because PDT precisely targets abnormal cells, it avoids the often horrific side effects of cancer chemotherapy and radiation therapy. These range from nausea to failure of the immune system and internal organs. With Photofrin, the main side effect is sensitivity to the sun, and patients get around it by avoiding direct sunlight for four to six weeks. Researchers say newer-generation PDT drugs will clear from the body faster, reducing sensitivity.
Such confidence is grounded in more than 20 years of research on PDT. Dr. Thomas J. Dougherty, a cancer researcher at Roswell Park Cancer Institute in Buffalo, N.Y., developed Photofrin, the first PDT drug, in 1981. Early clinical trials were promising, but clinicians lacked affordable, easy-to-use light sources. By the 1990s, several laser companies had solved that problem, and serious clinical testing resumed.
PDT is far from a cure-all. Unlike chemotherapy, PDT cannot chase down cancer cells that have metastasized throughout the body. And the light used with such drugs as Photofrin doesn't penetrate very deeply. Using catheters, doctors can reach some internal organs. Even so, they can do only limited damage to a large tumor.
PDT's greatest promise is with early-stage cancer patients. But the FDA, following its usual practice, is unwilling to clear wider use until it gets more data. So far, the only approved application is for patients dying of esophageal cancer.
Even in such cases, PDT's benefits can be remarkable. Dr. Charles J. Lightdale, director of clinical gastroenterology at New York's Columbia Presbyterian Medical Center, says PDT can clear the esophagus temporarily. Recently, he used it to help a patient eat cake at a child's wedding. "It's a very gratifying way to make [patients'] last days more tolerable."
More gratifying, however, would be the opportunity to save patients' lives. In Japan, doctors are using PDT to do just that. Japanese clinical trials of PDT using Photofrin found it produced "complete remission in 90% of patients with early lung cancer and in more than 80% of those with [early-stage] esophagus, stomach, and cervix cancers," says Dr. Harubumi Kato, chairman of the Surgery Dept. at Tokyo Medical College, who directed the trials. Now that the national health plan will cover costs, PDT will "spread across Japan," predicts Kato--aided by the fact that Japan's health-care system is geared toward early detection of cancer. Japanese smokers, he points out, are regularly screened for lung cancer.
The U.S. medical establishment takes the view that such screening doesn't appreciably reduce lung cancer deaths. This notion stems from a major U.S. study conducted in the early 1980s. But photodynamic therapy is helping to overturn the defeatist attitude. Dr. Denis A. Cortese, a lung cancer specialist at the Mayo Clinic in Jacksonville, Fla., worked on that study and initially endorsed its conclusions. But after more than a decade of using PDT experimentally, Cortese has done a dramatic about-face. His work shows that 43% of early-stage lung cancer patients treated with PDT remain disease-free for at least five years. He argues that the U.S. should rethink its approach to lung cancer, and other experts are chiming in. If the U.S. combined PDT with aggressive screening for early-stage disease, it could reduce mortality in one of the nation's top killers, says NCI's Pass.
EYES RIGHT. QLT hopes to get FDA approval for Photofrin in early-stage lung cancer as soon as next year. And that will be just the beginning. At the Minneapolis Ear, Nose & Throat Clinic, Dr. Merrill A. Biel calls PDT "a significant step forward" in the battle against early cancers of the mouth, throat, larynx, and tongue. His trials show cure rates of up to 95% with no permanent side effects. Other doctors think PDT could be effective on cancers of the skin, prostate, and even the brain, as well as a precancerous condition called Barrett's esophagus that afflicts 1 million Americans.
One of the most promising application areas is an eye disease called age-related macular degeneration (AMD)--the leading cause of blindness in people over 60. More than 100,000 older Americans are struck with the worst form of this disease each year, and current treatments help only 20% of them. Preliminary research in the U.S. and Europe suggests that a PDT drug called BPD, produced by QLT, can stabilize or improve vision. QLT has licensed this application to Ciba Vision Ophthalmics, and Marc Ostro, a biotech analyst at UBS Securities Inc. in New York, says it could become PDT's biggest home run.
With the industry's two most advanced drugs sewn up--Photofrin and BPD--QLT is poised to become the first industry powerhouse. The company reported cumulative losses of $46 million on revenues of just $8 million over the past five years. But such losses are not uncommon in biotech, where even the most promising treatments may take a decade or more to find market acceptance. Now that Photofrin has been approved, QLT could break into the black as early as this year, predicts Christine Charette, an analyst at Nesbitt Burns Inc. in Toronto. By 2003, she projects rising royalty income could help QLT earn $116 million before taxes, on revenues of $180 million.
PROSTATE CURE. By then, QLT will have plenty of competition. PDT Inc.'s first drug--SnET2--has shown good results in tests on AIDS-related Kaposi's sarcoma and on enlarged prostates. The drug was licensed by Pharmacia's Italian subsidiary in July, 1995. Pharmacyclics, based in Sunnyvale, Calif., has a drug called Lu-tex that it claims can eliminate the plaque that obstructs blood vessels in atherosclerosis. And Dusa Pharmaceuticals is developing drugs that can be applied topically. These offer hope for removing unwanted hair and precancerous skin lesions.
For all its promise, PDT is sure to suffer growing pains. "The medical community is quite conservative in adopting new technologies," says Dr. Julia G. Levy, the prominent Vancouver scientist who co-founded QLT in 1981 and now is its CEO. She has a personal stake in the therapy: Her grandmother and mother lost their sight to macular degeneration. And because it's hereditary, "I know I will get it as well," she says. But Levy knows it will take years to conduct clinical trials and win regulatory approval for all the diseases she and others have targeted. In the meantime, other effective new treatments are sure to appear.
Stock analysts who watch these companies also have concerns. They anticipate a shakeout among PDT drugs as researchers establish which ones work best for specific diseases. That makes it very difficult to pick winners. Nonetheless, PDT's power to radically improve treatment of horrible diseases already is apparent. Melvin Francis experienced that power in his battle with esophageal cancer. Soon, there may be many more like him.