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FACTS ON RITUXAN: PRESENT AND FUTURE

In 1997, the U.S. Food and Drug Administration (FDA) approved Rituxan®, the first therapeutic monoclonal antibody to treat cancer.  This action ushered in a new approach to attacking lymphoma, with help from a time-tested disease-fighter, the immune system.

WHAT IS A MONOCLONAL ANTIBODY?

Antibodies are normal components of the body's immune system that can recognize and destroy foreign invaders such as bacteria and viruses.  Scientists can now produce monoclonal antibodies designed to recognize very specific targets, or antigens, that are present on certain kinds of cancer cells.  Rituxan was the first monoclonal antibody to receive FDA approval.

Therapy with a monoclonal antibody is an effective way of specifically targeting certain kinds of cancer cells, with a low degree of toxicity to normal cells.  Monoclonal antibody therapy is administered by intravenous infusion, generally on an outpatient basis.  Once in the bloodstream, monoclonal antibodies travel throughout the body and attach themselves to cells that have the specific target antigen, such as cancer cells.  This alerts the body's own immune system to recognize and help destroy the cancer cells.  Although some normal cells that also have the specific target antigen may be affected along with the cancer cells, the body can replace these normal cells following treatment.

HOW DOES RITUXAN TREAT LYMPHOMA?

Rituxan works by attaching onto lymphoma-forming immune cells called B cells, causing the B cells to commit cellular suicide, a process researchers call apoptosis.  The Rituxan antibody is drawn like a magnet to a cell-surface marker on B cells called CD20.  Luckily, only mature B cells display this marker, so treatment with Rituxan does not wipe out all the immature B cells that can still grow up and replenish this critical disease-fighting arm of the immune system.  Rituxan treatment spares all other cell types.  As such, side effects are limited and are usually only seen with the body's first exposure to this antibody-drug.  Patients may experience a flu-like reaction from the infusion of the drug, which is treatable if managed right away.  Promising results since 1997, along with clinical trials since then, have prompted the FDA to approve expanded labeling of Rituxan for non-Hodgkin's lymphoma (NHL).

Expanded Uses of Rituxan

In response to the outcome of clinical studies testing Rituxan, in February 2001, the FDA approved new product labeling for Rituxan.  New indications include Rituxan re-treatment (after a previous course of Rituxan therapy), a longer first-time treatment course (from four weekly treatments to eight weekly treatments), and the opportunity to treat larger tumors (so-called "bulky" disease).

I ALREADY RECEIVED RITUXAN TREATMENT FOR MY NHL CAN I BE TREATED AGAIN?

Yes.  A clinical trial testing the effectiveness of re-treating patients with Rituxan showed that a second or third course of the medicine was as safe and can be as effective as the initial treatment.

HOW MANY RITUXAN INFUSIONS ARE NECESSARY-AREN'T EIGHT INFUSIONS BETTER THAN FOUR?

Not necessarily, but more research is required to test this notion.  The expanded labeling of Rituxan okays an eight-week treatment regimen because a recent clinical study demonstrated that eight weeks of treatment for indolent (slow-growing) NHL was as good or better than treatment for half that time.  However, to determine whether the outcome is significantly better with an extended treatment, scientists need to perform much larger, randomized trials.  Randomized trials pit two treatments against each other, with a large enough number of patients so that researchers can be sure the difference is real enough to make an impact.

MY DOCTOR SAYS I HAVE BULKY DISEASE-WHAT IS THIS AND CAN I RECEIVE RITUXAN TREATMENT?

Several years ago, researchers defined bulky disease as NHL tumors greater than 10 centimeters in diameter.  Early clinical trials with Rituxan excluded patients with bulky disease in order to maintain a more even population of patients in those clinical studies.  Recently published studies in which clinical researchers treated patients with bulky disease that had either relapsed (the cancer returned) or was refractory (the tumor did not respond to previous treatment) showed that Rituxan can significantly shrink even large tumors, convincing the FDA to approve Rituxan use for both types of bulky disease.  Other ongoing studies are revealing that Rituxan may also be useful as a first-time treatment for bulky disease that is neither relapsed nor refractory.

ARE THE EXPANDED USES AS SAFE AS THE ORIGINAL TREATMENT REGIMEN?

Yes.  Clinical trials that prompted the FDA to approve the new product labeling showed that both longer Rituxan treatment and re-treatment were as safe and effective as the initially approved four-week treatment schedule.  It is important for you to be aware that while Rituxan is a very safe drug, some patients have experienced serious side effects.  Most of these are uncommon and treatable.  The most common side effect of Rituxan treatment is a flu-like reaction that if left untreated can progress to a serious immune reaction.  However, careful monitoring and rapid treatment of such reactions results in no adverse effects to the patient's health or to the Rituxan response.  A much rarer side effect, called paraneoplastic pemphigus (PNP), has been seen in a handful of patients who received Rituxan after the drug had already been approved (none of these incidents showed up during clinical testing).  PNP, initially a blistering skin rash - often of the face and/or mouth - can progress into a fatal immune reaction.  However, it is important to note that researchers have not established whether PNP is a consequence of the cancer itself rather than an effect of Rituxan treatment, and its occurrence is exceedingly rare.  Overall, all of the approved uses of Rituxan are very safe and well tolerated by NHL patients.

Tailoring Rituxan Treatment

Thanks to the generosity of the many cancer patients who gave their time and energy to participate in clinical trials, researchers are beginning to be able to tailor treatments for individual patients, based upon the nature of each patient's cancer history.  Physicians can only know if one treatment is better than another, or if a particular therapy works better in certain groups of patients, by doing those experiments in carefully controlled trials.

HOW CAN I GET THE MOST BENEFIT FROM RITUXAN TREATMENT?

It's not clear-cut.  Some patients may benefit from eight weeks of Rituxan treatment, but for others, four weeks of therapy may be just as effective.  Scientists suspect that bulky disease, or another type of cancer, chronic lymphocytic leukemia (CLL, for which Rituxan therapy is showing some promise for treatment), may simply require a higher blood level of the Rituxan antibody to adequately attack the cancer.  This is an issue you should discuss with your doctor.

MY DOCTOR TOLD ME MY NHL IS IN REMISSION-CAN I TAKE RITUXAN TO HELP KEEP THE LYMPHOMA AWAY?

Yes.  So-called "maintenance therapy," in which you receive a Rituxan treatment every six months or so, is safe and may even have beneficial effects.  Giving Rituxan in this way may delay the time until you need to be re-treated with chemotherapy, a tactic that could reduce side effects or prevent secondary problems that stem from chemotherapy treatment.  Further research is ongoing to determine the full spectrum of benefits from maintenance therapy with Rituxan, including whether the medicine can keep lymphoma at bay for longer periods.

WHAT ABOUT OTHER TYPES OF LYMPHOMA OR OTHER CANCERS?

Roughly half of patients with NHL have the slow-growing, or indolent, type of disease.  The other half have aggressive NHL, which spreads much more rapidly.  Until now, Rituxan has only been approved for use with indolent NHL.  To date, researchers have had success in curing aggressive NHL by other means (about 40 percent of patients with this form of NHL are cured after chemotherapy).  Early laboratory studies hinted that the combination of Rituxan with chemotherapy had additive effects, working better than either treatment alone.  Recent clinical studies have shown that Rituxan in combination with a chemotherapy treatment called CHOP (a mix of several different chemotherapy medicines) may cure more patients with aggressive NHL.  Since these two types of medications work in different ways, and Rituxan therapy has fewer toxicities, patients given such a combined therapy can get a more effective treatment of their cancer without increased side effects associated with a higher dose or an additional type of chemotherapy, for instance.

Rituxan has also been shown to be effective in treating CLL as well as a similar cancer, small lymphocytic lymphoma, especially if used soon after diagnosis and in combination with chemotherapy.  Early research with these cancers suggests that a longer dosing schedule with Rituxan may be more effective.  Current research is investigating the use of Rituxan in patients undergoing bone marrow transplantation; preliminary results have shown that the treatment is safe, but more studies are needed to determine whether Rituxan treatment adds any benefit to the transplant procedure.  Ask your doctor questions about what sort of treatment is best for you, and whether it makes sense to combine Rituxan therapy with chemotherapy.

Scientists are working hard to figure out the best way to use Rituxan to treat patients with NHL and other types of cancer, either alone or in combination with other types of medicines.  Many clinical studies are underway to determine the best treatment schemes for certain types of patients.  If ongoing trials prove that Rituxan works well at any time during the course of lymphoma, the next step may be to approve its use as a front-line therapy in newly diagnosed patients who have never been treated with any other cancer treatment.

 

Revised April 2002