FDA approves first drug in a decade for NHL

NOVEMBER  1997

    Thousands of patients with an incurable type of non-Hodgkin's lymphoma won their first new weapon in a decade Wednesday.

   The Food and Drug Administration approved a novel, genetically engineered drug to attack the immune system cancer with far fewer side effects than standard treatment.

   Rituxan is not a cure, but the FDA said it has an "excellent" success rate in shrinking tumors safely.

   The approval makes Rituxan the nation's first anti-cancer monoclonal antibody -- a long-awaited biotherapy in which specially manufactured antibodies bind to cancer cells and trigger the immune system to do the killing instead of toxic chemicals.

   One patient who tested Rituxan called the approval "something to celebrate this Thanksgiving."

   "Even though my type of lymphoma is still considered incurable, Rituxan has renewed my hope of raising my three children," said Dr. Wendy Harpham, a Richardson, Texas, physician who failed other treatments before Rituxan therapy put her cancer in remission.

   About 240,000 Americans have non-Hodgkin's lymphoma, a cancer of the lymph system that targets vital white blood cells. Many patients are successfully treated. But about half of them have an incurable form called low-grade non-Hodgkin's that causes repeat relapses over six or seven years.

   These patients try high doses of chemotherapy, radiation and bone marrow transplants that can cause severe side effects, particularly when these treatments also kill healthy cells that get in the way.

   Rituxan, on the other hand, is made from a genetically engineered mouse antibody designed to be a more specific treatment. Scientists don't know exactly how it works, said FDA monoclonal antibody chief Kathryn Stein. But ultimately these antibodies zero in on the white blood cells involved in non-Hodgkin's lymphoma and trigger their death.

   "This is the first of what we hope will be many monoclonal antibodies for tumor treatment," she said.

   In a study of 166 patients with advanced cancer, 48 percent had their tumors shrink by at least half. Six percent of patients had complete remissions. Half the successful patients remained stable for more than 11 months, a rate that Stein called "excellent."

   Rituxan therapy does not require hospitalization. Manufacturers IDEC Pharmaceuticals and Genentech Inc. say Rituxan, known chemically as rituximab, will be available within a month. A complete course of four weekly transfusions will cost roughly $9,000, comparable to many chemotherapies.

   Rituxan has some risks. It can kill healthy white blood cells as well as cancerous ones, meaning patients could suffer infections although no unusual rates have appeared so far, said Dr. Peter McLaughlin of the M.D. Anderson Cancer Center, the drug's lead investigator. Those cells grow back on their own within a year.

   Additionally, most patients have temporary and mild flu-like symptoms, such as fever and chills, one to two hours after the first infusion, as their bodies learn to recognize the new antibody, he said.

   So few side effects make Rituxan a prime candidate to give to lymphoma patients in addition to chemotherapy, hoping for a one-two punch against the disease, McLaughlin said. Doctors already are studying how well such a combination could work, as well as the feasibility of giving it to earlier patients instead of waiting until they relapse.

   But for patients today, Rituxan promises to buy some time. Harpham says if she hadn't gotten to test the drug, she would already have tried her last option -- a bone marrow transplant that she still can turn to if she has another relapse.

   Still, "Rituxan has been the closest answer to my prayers so far," she said.

How and why Rituxan works

   Low grade non-Hodgkins lymphoma (NHL) cells are not easy to spot by your cancer-fighting immune system. Rituxan works by attaching a biological "flag", called a monoclonal antibody, to proteins which are on the surface of the lymphoma cells. This makes it easier for your immune system to find the lymphoma cells and destroy them. This process is called biological response therapy or immunotherapy. The treatment acts by stimulating your body's own ability to destroy cancer cells instead of relying on more toxic and less specific drugs. Thus there are different and generally less toxic side effects than with standard chemotherapy.

   Rituxan is administered as an intravenous infusion (IV) once weekly for four weeks. You may have received chemotherapy or blood transfusions this same way in the past.

   Many patients receive a second four week course of Rituxan after a brief "rest" period.

   Rituxan had a complete or partial remission rate of 48% when tested in the early trials.

   What you might experience while on treatment

   Rituxan may cause the following discomforts: weakness, fatigue, sweating, chills and shaking (known as "rigors"), headache, breathlessness, racing heart, and muscle aches. Some people also develop a rash over various parts of their body, but this is not as typical.

   Most patients experience some discomfort while Rituxan is being infused. These symptoms, although upsetting, are expected and will be managed by your physician and nurse by taking over-the-counter remedies (Benadryl and Tylenol) just prior to starting treatment to reduce any discomfort. It is important to remember that being alarmed by these symptoms is understandable. They need not frighten you since they are part of the response to treatment and indicate that the treatment is doing its work. If you have concerns, please talk with your physician or nurse.

   For some patients some of these symptoms can occur a day or two following therapy. All symptoms need to be reported to your physician who will make the necessary plans to treat them and reduce discomfort for the following treatment cycles.

  Tips to help you with the Rituxan treatments

   You will receive four infusions of Rituxan at weekly intervals. Treatment generally take longer in the first session because the Rituxan is given to you slowly. This allows the medical staff to observe your reactions and make adjustments as necessary. For the first session this may take 4 to 5 hours during which time you will be either in a comfortable reclining chair, or in a bed. One of the medications you will be given (Benadryl) makes you drowsy and so it is necessary to have someone accompany you for each infusion in order to drive you home afterwards. All treatment is done on an outpatient basis.

   Lying quietly for several hours can be hard for even the best of patients and so planning for diversions during this time is a good idea. Some people bring along a book or magazine to read, others a crossword puzzle, many folks like to use a portable audiotape/CD player with headphones to help them while away the time.

   Most centers where you will be treated have soft drinks or snacks available, but you may prefer to bring along your own favorites. The treatments are likely to go through a lunch hour and so you may want to check with your doctor or nurse about having a snack.

   Bringing your own pillow or cover can also make the experience more comfortable, although everything you will need is readily available on site.

   Because your visits to clinic will be regular you are likely to strike up new acquaintances during your infusion sessions. Some people use these opportunities to share their experiences with treatment, and often pick up invaluable new insights of their own.

   You may want to use the audiotape relaxation and visualization exercises which accompany this brochure. These techniques are often useful ways of overcoming boredom and increasing a sense of wellbeing and optimism.

  Finally, remember, if you experience any feelings of discomfort or unusual sensations let your nurse know immediately so that changes may be made in the infusion process.

   Authored by Brian Stabler of Chapel Hill, North Carolina

   Complete article at: http://cancer-info.com/rituxan.htm

   Professor Stabler is a professor and specialist in stress at the University of North Carolina Medical School, and is an 8-year survivor of Non-Hodgkin's Lymphoma. Brian successfully under went Rituxan therapy in North Carolina earlier this year of 1998.