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Rituximab

Rituximab

Definition

Rituximab is a humanized monoclonal antibody that selectively binds to CD20, a protein found on the surface of normal and malignant B cells and is used to reduce the numbers of circulating B cells in patients who have B-cell non-Hodgkin's lymphoma (NHL). Rituximab is sold as Rituxan in the United States.

Purpose

Rituximab is a monoclonal antibody used to treat NHL characterized by overgrowth of B cells, the cell involved in about 85% of NHL malignancies. Of all the B-cell cancers more than 90% express the CD20 protein on the cell surface, a requirement for the proper function of rituximab. By binding the CD20 protein on the B cell, the antibody targets it for removal from the circulation. Based on data gathered in the laboratory developers believe that rituximab triggers both cell-mediated and complement-mediated means to kill the B cells, two different methods that the immune system uses to eliminate foreign cells. Binding of the antibody may also trigger apoptosis, or programmed cell death, of the B cells.

Rituximab has been most effective against low-grade (indolent) or follicular B-cell NHL. Low-grade (slow progression) NHL often responds well to initial treatment, but frequently relapses, making rituximab a welcome addition to the treatment options. Additionally, rituximab has been used for a second course of treatments after relapse with some success. As most patients with NHL are in stage III or IV by the time of diagnosis and treatment, experience with rituximab treatment are primarily with those stages of the disease.

As of spring 2001 clinical trials were being held testing the ability of this drug to work against several other types of cancers, including newly diagnosed NHL, intermediate-or high-grade (aggressive) NHL, AIDS-associated NHL, Waldenström's macroglobulinemia , Hodgkin's disease , hairy cell leukemia (HCL), chronic lymphocytic leukemia (CLL), multiple myeloma , mantle cell lymphoma , and large cell lymphoma.

Description

Rituximab is produced in the laboratory using genetically engineered single clones of B cells. Like all antibodies it is a Y-shaped molecule that can bind to one particular substance, the antigen for that monoclonal antibody. For rituximab that antigen is CD20, a protein found on the surface of B cells. Rituximab is a humanized antibody, meaning that the regions that bind CD20, located on the tips of the Y branches, are derived from mouse antibodies but the rest of the antibody is human sequence. The presence of the human sequences helps to reduce the immune response by the patient against the antibody itselfa problem seen when complete mouse antibodies were used for cancer therapies. The human sequences also help to ensure that the various cell-destroying mechanisms of the human immune system are properly triggered with binding of the antibody.

In 1997 Rituximab was the first unconjugated (not linked to a radioactive isotope or toxin) antibody approved for use by the FDA to treat cancer. It is specifically approved for treatment of low-grade or follicular B-cell NHL. Administration of the antibody resulted in either complete or partial responses in a little less than half of those patients.

Rituximab can be used alone or in combination with other chemotherapeutic drugs. Specifically, very good results have been seen when used in combination with the CHOP chemotherapy regimen (cyclophosphamide , doxorubicin , vincristine , and prednisone). When used in combination, dosages of the antibody given before beginning chemotherapy, alternating with the other drugs, then after the chemotherapy as a "mop-up" have proven effective.

There are a number of clinical trials in progress testing the ability of rituximab to work in combination with other chemotherapy drugs, treatments, and cytokines. Some substances and treatments being tested include interleukins 2 and 11, stem cell transplantation, radioimmunotherapy, vaccination, and a wide variety of other chemotherapy combinations.

Recommended dosage

The recommended dosage for patients with low-grade or follicular NHL is 375 mg/m2 infused intravenously. The infusion is given at weekly intervals for four total dosages. Acetominophen and diphenhydramine hydrochoride are given 30-60 minutes before the infusion to help reduce side effects. If given as a retreatment the dosage is the same. Clinical trials were ongoing in 2001 to help clarify the ideal dosage and treatment schedule for this drug. Generally, decrease in symptoms occurs at an average of 55 days after the last administration of the antibody.

Precautions

Serious (even fatal) infusion reactions, especially with the first infusion, have been known with this drug. There are a number of patient conditions that can make taking this drug more dangerous. Specifically, heart problems such as arrhythmias and high blood pressure, and the medications taken to treat those conditions, can be a problem with this treatment.

Side effects

The majority of side effects occur after or during the first infusion of the drug. Some common side effects include dizziness, feeling of swelling of tongue or throat, fever and chills, flushing of face, headache, itching , nausea and vomiting , runny nose, shortness of breath, skin rash, and unusual fatigue .

Less common side effects include black, tarry stools; blood in urine or stools; fever or chills with cough or hoarseness; lower back or side pain, or painful or difficult urination; pain at place of injection; pinpoint red spots on skin; red, itchy lining of eye; swelling of feet or lower legs; unusual bleeding or bruising; and unusual weakness.

Although they are very rare this drug does have serious side effects such as chest pain and irregular heartbeat, particularly in patients already having heart conditions. It can also cause serious effects on the blood cells such as low red blood cell count (anemia ) and low white blood cell count (neutropenia ). Additionally, this drug has caused low blood pressure (hypotension).

In patients with high tumor burden (a large number of circulating malignant B cells) this drug can cause a side effect called tumor lysis syndrome (TLS). Thought to be due to the release of the lysed cells' contents into the blood stream, it can cause a misbalance of urea, uric acid, phosphate, and calcium in the urine and blood. Patients at risk for this side effect must keep hydrated and can be given allopurinol (an anitgout medication) before infusion.

Interactions

There have been no formal drug interaction studies done with rituximab.

See Also Monoclonal antibodies

Michelle Johnson, M.S., J.D.

KEY TERMS

Antibody

A protective protein made by the immune system in response to an antigen, also called an immunoglobulin.

Apoptosis

Internal system for cell death, also called programmed cell death.

CD20

A protein found on the surface of normal and malignant B cells.

Humanization

Fusing the constant and variable framework region of one or more human immunoglobulins with the binding region of an animal immunoglobulin, done to reduce human reaction against the fusion antibody.

Monoclonal

Genetically engineered antibodies specific for one antigen.

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"Rituximab." Gale Encyclopedia of Cancer. . Encyclopedia.com. 18 Aug. 2017 <http://www.encyclopedia.com>.

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"Rituximab." Gale Encyclopedia of Cancer. . Retrieved August 18, 2017 from Encyclopedia.com: http://www.encyclopedia.com/medicine/encyclopedias-almanacs-transcripts-and-maps/rituximab

rituximab

rituximab (rit-uks-i-mab) n. a monoclonal antibody administered by intravenous infusion to treat some types of non-Hodgkin's lymphoma, either alone (in cases that have not responded to standard chemotherapy) or in combination with other anticancer drugs. Trade name: MabThera.

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"rituximab." A Dictionary of Nursing. . Encyclopedia.com. 18 Aug. 2017 <http://www.encyclopedia.com>.

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"rituximab." A Dictionary of Nursing. . Retrieved August 18, 2017 from Encyclopedia.com: http://www.encyclopedia.com/caregiving/dictionaries-thesauruses-pictures-and-press-releases/rituximab