What's Become of Interferon?

By Claudia Wallis

Few drugs have stirred more excitement and hope than interferon, which was widely heralded in the late 1970s as a potential cure for cancer and viral diseases. Painstakingly extracted in minute amounts from living cells, the substance showed great promise in laboratory tests. And by the early 1980s, genetic engineering had made possible the production of interferon in quantities large enough to begin extensive testing in humans. But soon afterward disillusionment set in. Although interferon slowed the growth of some tumors, it had no effect on others, and it often produced disturbing flulike symptoms. Interferon, it seems, was not a magic bullet but, as Dr. Jules Harris, a cancer researcher at Chicago's Rush Medical College, puts it, "a complex group of drugs with complex side effects."

Undaunted, scientists continued to test the enigmatic substance. "People do not realize how slowly research progresses," says Dr. Jordan Gutterman, a leading interferon investigator at Houston's M.D. Anderson Hospital. "You don't go to the moon on the first rocket." At a meeting of the American Society of Clinical Oncology in Houston, it became clear that interferon has at the very least had a successful launch, and may be beginning to fulfill some of its early promise.

The big news in Houston was the remarkable success of alpha interferon (one of the three major types of the substance) in fighting an unusual cancer known as hairy-cell leukemia (because of the hairy appearance of the malignant cells). The disease is usually treated by removing the patient's spleen, but this seems to help in only about half the cases. For the other half, there was no viable treatment until interferon was tried. Two reports presented at the conference showed that interferon can be effective in up to 90% of hairy-cell patients, greatly reducing or completely reversing all signs of the disease. "We saw dramatic responses even in very advanced cases," says Dr. Harvey Golomb of the University of Chicago, who directed one study. Though interferon did produce flulike side effects, these generally disappeared after a few days of treatment. Says Dr. Jorge Quesada of M.D. Anderson, who led the other study: "We have patients who run five to ten miles a day while on interferon."

Although hairy-cell leukemia affects only 400 Americans a year, Golomb and Quesada point out that it is just one of several cancers that affect a class of white blood cells called B-cells; collectively these cancers strike 35,000 Americans a year. Says Golomb: "This may be a window into a family of disorders." Interferon has already proved useful in treating multiple myeloma, a B-cell-related cancer of the bone marrow that annually afflicts more than 8,000 Americans.

Interferon's performance against other forms of cancer has been inconsistent, but when it does work, the results can be dramatic. It has produced complete remissions (though not necessarily permanent cures) in advanced cases of kidney cancer; in malignant melanoma, a lethal form of skin cancer; and in Kaposi's sarcoma, a skin cancer that often strikes AIDS victims. In one study reported in Houston, just five out of 52 patients with advanced melanoma were successfully treated with interferon. But this handful was extraordinary: all signs of cancer disappeared within four months, even though the disease had spread to such organs as the liver and lungs.

Even the most enthusiastic proponents of interferon concede that it is a difficult substance to work with, far more complex than traditional anticancer drugs. Just getting the dosages right can be tricky, and they are different * with each disease. "More is not better with the interferons," says Mathilde Krim of New York City's Memorial Sloan-Kettering Cancer Center. "Giving too much can have the opposite of the desired effect."

Doctors suspect that interferon may be most effective not as a solo performer but in conjunction with other medications. "No single drug is the optimal treatment for any common cancer," says Dr. Ernest Borden of the University of Wisconsin. "The big question over the next five years will be how to combine interferons with other treatments." Particularly promising, says Borden, is combining several types of interferon, since one form seems to enhance the effects of another. Doctors are also excited about the possibility of using interferon together with another powerful, naturally occurring anticancer agent called tumor necrosis factor. "Interferon and TNF together add up to more than the sum of their parts," says Dr. Lloyd Old, of Sloan-Kettering, who discovered TNF 14 years ago. Interferon may work synergistically with certain cancer drugs and with radiation therapy.

Some of interferon's failings may stem from the fact that it has been tried mainly in the most desperate cases of cancer, on those for whom no other treatment has worked. "These are the worst possible conditions in which to test it," says Krim. She and others think that interferon holds greater promise for patients with early cancers and those whose immune systems have not been weakened by radiation treatment or chemotherapy. Other potential uses for interferon: heading off the recurrence of tumors after they have been surgically removed, and preventing precancerous conditions like cervical dysplasia from progressing into full-blown cancers. But much more testing lies ahead, says Dr. Ronald Herberman, chief of biological therapeutics at the National Cancer Institute, and the world will have to wait a bit longer to see what interferon can do. In the encouraging results so far, he says, "we may be seeing just the tip of the iceberg."