Treatments > Rituxan

Basics | Resources | Who is Rituxan for? | How is it made? | Scheduling Rituxan
What should I expect? | How does Rituxan work? | Side Effects |  About cd20
How long does it take to respond? | What is the expected response rate? How long does it take normal b-cells to recover?  

Asheducationbook.org - Articles on Rituxan

Antibodies are the proteins made by the body's immune system cells. These proteins recognize and attack specific foreign invaders, such as infectious germs. The body makes millions of antibodies, each of which has a specific shape to recognize and bind to a foreign molecule. Many years ago, scientists discovered how to make large quantities of identical antibodies - hence ''monoclonal'' - in mice. 

Rituxan® (Rituximab/anti-cd20/MabThera) is an antibody that may induce killing of b-cells - malignant and normal - by inducing self killing, or by flagging the cells for attack by the immune system:

     
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Rituxan is the first monoclonal antibody found to be effective and safe for the treatment of cancer in the United States.

The standard recommended dose of Rituxan is 375 mg/m² given as an IV infusion weekly for 4 doses.
The "/m2" means per meter squared ... that is, the actual dose is calculated by the size of the patient.

When your body detects something that does not belong, such as bacteria, one way it eliminates the threat is to produce antibodies that bind to the protein shapes that are specific to the pathogen.  

Rituxan is a man-made antibody that binds to all CD20-expressing B lymphocytes, both malignant and nonmalignant (cancerous and normal). 

CD20 is a receptor (or antigen, marker, protein) ... with a specific shape, that's found on mature B lymphocytes, but not on stem cells, plasma cells, or other tissues ... 

...  importantly, the cd20 receptor is not found on precursor B cells - immature b-cells which can later mature to replenish the supply of normal mature b-cells. 

In the initial Rituxan trials, circulating mature B lymphocytes were depleted within the first three doses with sustained depletion for up to 6 to 9 months post-treatment in 83% of patients. Also, in some patients there were sustained and statistically significant reductions in both serum IgM and IgG (antibody) levels observed from 5-11 months following Rituxan administration. 

"Anti-CD20 therapy has had a truly dramatic impact on treatment and outcome of patients with follicular lymphoma. Unfortunately, the majority of responses to single-agent rituximab are incomplete, and all patients with follicular lymphoma will experience disease progression at some point
following rituximab therapy.

Rituximab has multiple mechanisms of inducing in vivo cytotoxicity, including antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDCC), direct apoptotic signaling, and possible vaccinal effects. Rituxan also increases the sensitivity of lymphoma cells to several chemotherapy agents.

The cellular microenvironment within follicular lymphoma has a profound impact on which mechanism is dominant, and confers resistance in many situations. Both tumor-associated and host-associated factors also contribute to rituximab resistance."  - Unique Toxicities and Resistance Mechanisms Associated with Monoclonal Antibody Therapy, Jonathan W. Friedberg See asheducationbook.org


How Rituxan may induce lysis (killing) of lymphoma cells:

apoptosis is a natural mechanism by which cells "commit suicide" when they have outlived their purpose, become defective, or have aged.  Apoptosis prevents cells from accumulating and forming tumors.  Understanding of the control of apoptosis in normal and malignant cells will help to improve the diagnosis and treatment of malignancies. The goal of many treatments, including chemo and and antibody-based therapy is to induce malignant cells to undergo apoptosis.  Picture it  

antibody-dependent cell-mediated cytotoxicity (ADCC) - An immune response triggered by the presence of antibody  (Abs) coating the target cell (such as Rituxan). Upon binding its antigen, the Antibody's Fc region is exposed and will bind its receptor on the NK cell (or other effector cells) to form a bridge. Once the bridge is formed, a poorly understood lytic (killing) signal is delivered to the target cell by the effector cell, resulting in its demise. - (adapted from the Merck Manual)  

complement-dependent cytotoxicity (CDC): A mechanism of killing cells in which antibody bound to the target cell surface fixes complement, which results in assembly of the membrane attack complex that punches holes in the target cell membrane resulting in subsequent cell lysis. 

vaccinal effect - when a therapy leads to recognition of tumor antigens (abnormal proteins) as foreign leading to an attack of the remaining tumors by effector cells in the immune system.

~ KarlS

Recommended Resources:

Prescribing Details

Access to Drug

Background on Use

Rituxan^® (Rituximab) is indicated for ( www.rituxan.com/lymphoma/HCP/index.jsp ) Jan 2007  

	the treatment of patients with relapsed or refractory, low-grade or follicular, CD20-positive,  B-cell, non-Hodgkin's lymphoma.
	the first-line treatment of diffuse large B-cell, CD20-positive, non-Hodgkin's lymphoma  in combination with CHOP or other anthracycline-based chemotherapy regimens.
	the first-line treatment of follicular, CD20-positive, B-cell non-Hodgkin’s lymphoma in combination with CVP chemotherapy.
	the treatment of low-grade, CD20-positive, B-cell non-Hodgkin's lymphoma in patients with  stable disease or who achieve a partial or complete response following first-line treatment  with CVP chemotherapy.

See Indications below

Rituxan in Canada?  cancercare.on.ca

Dose: "Many studies have been performed to optimize its dose and schedule, and more are ongoing. The dose of 375 mg/m² has become standard, mainly because it shows activity and has little associated toxicity." 1

Interval between treatments and courses: "The half-life of rituximab is about 1 week; median duration of persistence in the blood at active levels is of about 3 months: .... A prospective PK-based study by Gordan et al addressed the optimal interval between administrations. ....  the great majority of patients could maintain active levels of drug with an infusion interval of 3 months, and all of the patients could be kept with blood levels in this range if they were treated every 2 months. We can therefore assume that an infusion of rituximab every 2–3 months should be sufficient to maintain tumors constantly exposed to active concentrations of the drug. This is actually the schedule that was chosen by many cooperative study groups for their maintenance strategy." ¹

The goal of maintenance therapy is to "prolong the duration of chemotherapy-obtained remissions. "Data on long-term administration of rituximab are scarce and we need to await the results of prospective randomized trials of maintenance versus no maintenance before we can recommend this treatment as standard." ¹ 

What should I expect, and how should I prepare for my first 
treatment with Rituxan?

Preparations

Monitoring your reactions

The above Rituxan checklist - Print version 

Rituxan circulates in the lymphatic system and tissue. It binds specifically to the CD20 antigen, a molecule present on the surface of the normal and malignant pre-B and mature B cells. This binding can be imagined as a lock fitting a key. More than 90 percent of B-cell NHL express CD20. Once bound to B-cells, Rituxan induces lysis (destruction of the cell) through several possible mechanisms: 

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