Barbara Boughton    Medical & Lifestyle Writer

Barbara is a consumer health writer who has won more than a dozen journalism awards for her work.

She has contributed to national magazines and Web sites such as CBS Healthwatch, On Health.com, Consumer Reports, and Alternative Medicine magazine.

Read Barbara's consumer health articles on Associated Content!

The Emotional Payback of Walking

Too Much of A Sweet Thing: What's Wrong With Sugar

Five New Ways to Treat Cancer: Monoclonal Antibodies  

One of Barbara's health and medical articles for In Touch magazine, a magazine for cancer patients. Part of a 5-part series on cutting-edge cancer treatments, this article concerns monoclonal antibody therapies.   

In March 2000, Raymond Lutzker’s doctors ran out of hope. "They told me that there were no other options left to treat my cancer, and I should prepare for the inevitable," the 71-year-old says now. Since he was diagnosed with CLL (chronic lymphocytic leukemia) 5 years ago, Lutzker had endured a series of disappointing treatments, including several types of chemotherapy and surgery to remove his spleen.

Still, when he heard the desperation in his doctors’ voices last year, Lutzker turned to the Internet and found out about a promising new type of drug called Campath. He entered a clinical trial at Stanford University to take the drug. And then, to everyone’s amazement, Lutzker’s cancer suddenly stabilized. Thanks to this novel drug the retired optometrist from San Rafael, California, was spared a death sentence.

Although his cancer is not cured, Lutzker is able to pursue a busy life of volunteer work, and looks hopefully toward the future. "Now my life is livable and survivable," he says, "and I get to hang around until the next remarkable drug comes along."

New Cancer Weapon

Campath is one of a group of promising new medications called monoclonal antibodies (MAbs). They contain manufactured antibodies—specialized proteins produced by the immune system—that home in like guided missiles to attack cancer cells. (See "How MAbs Work," at right.)

Unlike chemotherapy, these new target-specific drugs don’t damage normal cells. So far the FDA has approved four MAbs for cancer treatment: Rituxan, for B-cell non-Hodgkin’s lymphoma; Herceptin, for breast cancer; Mylotarg, for acute myeloid leukemia; and Campath, for chronic lymphocytic leukemia.

"Monoclonal antibodies are very useful, and even impressive, weapons in the fight against some cancers," says Marshall Lichtman, MD. Dr. Lichtman is executive vice president for research and medical programs at the Leukemia and Lymphoma Society. "They have a very important role today in advancing cancer treatment," he says.

MAb researchers were especially excited last year at the annual meeting of the American Society of Clinical Oncology, the world’s largest gathering of cancer specialists. What piqued their interest was the monoclonal antibody called Cetuximab, now being studied in colon cancer. In a clinical trial of 121 patients whose cancer had recurred after initial chemo treatment, nearly one-quarter of those treated with Cetuximab plus chemo saw their tumors shrink by at least 50 percent. "We got responses in the sickest of patients, responses we cannot get with chemotherapy alone," says Leonard Saltz, MD, co-leader of the colorectal disease management program at New York City’s Memorial Sloan-Kettering Cancer Center. "This drug will be a very active weapon in the war against colon cancer, the number two killer in the United States."

Cetuximab is particularly important because it targets a protein found on cancer cells called EGFR, or epidermal growth factor receptor. EGFR promotes tumor growth; most normal cells contain it. But many kinds of cancer cells have an excess amount of EGFR, which makes it easy for the cells to spread and grow. Studies show that 70 to 80 percent of cancers such as colon, lung, head and neck, and prostate cancer have too much EGFR. Cetuximab could effectively target these tumors, says Dr. Saltz. The drug is now in phase 3 clinical trials for colon, throat, and head and neck cancers. These large trials should give scientists—and patients—the answers they are hoping for.

Another impressive MAb study was presented last year at the American Society for Hematology meeting. The drug Rituxan given with chemotherapy shrank cancers in 76 percent of 400 previously untreated patients with B-cell non-Hodgkin’s lymphoma. In contrast, only 60 percent of the patients who received chemotherapy alone experienced tumor shrinkage. "The findings were dramatic," says Ron Levy, MD, chief of the division of oncology at Stanford, and the first scientist to study Rituxan in clinical trails. "The results were much better than expected. We’re learning how to best use these drugs for the benefit of patients."

Scientists believe that monoclonal antibodies like Rituxan may make cancer cells more susceptible to chemo. "They seem to have a synergistic effect," says Leonard Presta, PhD, staff scientist at Genentech, the drug firm that helped develop Herceptin and Rituxan. MAbs such as Rituxan are especially effective when used with chemo. And indeed, such combination therapies may one day be the rule for cancer treatment. "It will take us forward in cancer treatment now and in the future," says Kanti Rai, MD, chief of hematology and oncology at Long Island Jewish Medical Center.

MAbs used alone are usually as effective as chemotherapy. But they generally cause fewer and more short-term side effects than chemo. "Monoclonal antibodies provide patients—especially those with aggressive cancers for whom chemotherapy can be harrowing—an important alternative," says Eric Sievers, MD. Dr. Sievers led some of the clinical trials on Mylotarg at the Fred Hutchinson Cancer Research Center in Seattle.

Side Effects

Monoclonal antibodies can produce side effects similar to chemo, such as lowered white and red blood cell counts, making the patient vulnerable to infections. Some people also get temporary "infusion reactions." That is, when the drug is administered they break out in a rash or feel feverish and chilled. Yet overall, MAb therapy is less disruptive to normal life than chemotherapy. In fact, unlike chemo, these drugs cause no baldness, vomiting, or fatigue, for instance.

After receiving intensive chemo, radiation, and immune-boosting treatments, Wendy Harpham took Rituxan for the first time in 1993 to treat her non-Hodgkin’s lymphoma. Though she did have low blood pressure and some queasiness while the drug was given—common side effects of Rituxan—by the next day she was back to her usual routine. A physician who put her practice on hold when she was diagnosed with cancer, she was fully able to take care of her three young children after getting Rituxan, she says (see "Taking Care of the Kids"). In contrast, her previous chemo treatments had given her uncontrollable nausea, vomiting, and headaches. "Not only did Rituxan control my cancer, but it did it without making me sick," says Harpham, who now writes consumer medical books. "It was almost unbelievable."

Rituxan is what’s known as a "naked," or pure, antibody. Some MAbs, however, are attached to chemo or radioactive agents to increase their cancer-killing effectiveness. For instance, Mylotarg is attached to a powerful chemo agent called calicheamicin. The antibody targets leukemic blast cells and delivers calicheamicin to them, damaging their DNA. As a result the leukemic cells can’t survive. "Mylotarg is like a Trojan horse that aims for a cancer cell, and when it reaches its destination, releases calicheamicin to destroy it," says Dr. Sievers.

Other new drugs, such as Bexxar and Zevalin, are MAbs attached to radioactive atoms that help destroy the cancer. These drugs are now in clinical trials for non-Hodgkin’s lymphoma. They’ve proven very effective for patients with advanced, recurrent cancer. One recent trial was led by researchers at the Mayo Clinic in Rochester, Minnesota. The cancers of 73 percent of patients with B-cell non-Hodgkin’s lymphoma shrank by at least half when treated with Zevalin. Results of the study were announced last year. The trial is ongoing, but now closed to new patients. (Editor's note: Zevalin was approved for marketing by the FDA in February 2002, after this article went to press.)  

Several FDA-approved MAbs are used to treat advanced cancer. But, increasingly, these new drugs are being studied as first-line and "add-on" cancer therapies. "It’s extremely important that we start bringing these novel drugs to cancer patients undergoing treatment for the first time," says Edith Perez, MD, director of the breast cancer program at the Mayo Clinic in Jacksonville, Florida.

Dr. Perez is overseeing a phase 3 clinical trial of Herceptin in 3,000 women with previously treated aggressive breast cancer. Scientists want to know whether the drug decreases the likelihood of breast cancer recurrence and increases survival. Herceptin is a MAb designed to destroy breast cancer cells that produce an excess of a protein called HER2. The protein prods cancer cells into growing rapidly, and is found in about one-third of women with breast cancer.

In the March 15, 2001, issue of The New England Journal of Medicine, scientists reported on a clinical trial of over 450 women with metastatic breast cancer. Half the women received Herceptin and several different types of chemotherapy, while half received chemo alone. Herceptin increased survival time significantly.

Yet the trial also pointed out that Herceptin might have serious side effects. Some of the patients who received Herceptin in combination with the chemo drug Adriamycin (doxorubicin) experienced heart problems, shortness of breath, and fatigue. Researchers hope to reduce these adverse side effects by using doxorubicin in smaller amounts and in sequence with Herceptin, and monitoring patients carefully, says Dr. Perez. The heart problems can be treated, she says, and are usually reversible. "We want to find out if the risk of heart failure is a significant problem in future trials," says Clifford Hudis, MD, chief of the breast cancer service at Sloan-Kettering. "But overall, Herceptin is less toxic than other therapies in use today."

Monoclonal antibodies aren’t yet the silver bullet many would wish for. Most of them wipe out cancer for a year or more, but then patients have to take them again to keep the disease at bay. Yet there is real hope among scientists that repeat treatments may control many patients’ cancer for years. Just ask Minerva Boor. In 1998, after several rounds of chemo, radiation, and a bone marrow transplant for metastatic breast cancer, she was treated with Herceptin. Her only side effect from the drug: a slight headache afterward.

"At the time I got Herceptin, I didn’t know what else I could do to fight this cancer," says Boor, now 40, a supervisor for the probation department in San Antonio, Texas. "There were times my family didn’t think I would make it," she says. "But now because of Herceptin I have been free of cancer for 3 years, and that’s a real gift."

Barbara's health articles include:

An award-winning profile of Karen Graham, cancer advocate, for American Profile magazine

How to Assess Your Risk of Cancer on the Web, a personal essay for Cure Today Magazine,

Determining Cancer Risk Online