Re: [MOL] rituxin/REPLY [02272] Medicine On Line


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Re: [MOL] rituxin/REPLY



Welcome to our forum Roger.  Hope this information helps you, warmly, your friend, lillian
 
 

Rituximab for Refractory Non-Hodgkin's Lymphoma

From issue No. 243 (December, 1997) of Medical Sciences Bulletin

Issue 243 Contents Other Articles *


About 30,000 new cases of non-Hodgkin's lymphoma (NHL) occur each year in the US and the incidence appears to be increasing. These tumors represent the most common neoplasms among perons aged 20-40 years. With the increasing incidence of AIDS, the number of cases of NHL has increased. Some animal studies suggest that lymphomas may have a viral etiology, although this association varies with the type of lymphoma. Genetic predisposition has been found for certain lymphomas. More than two-thirds of patients with NHL present with persistent, painless, peripheral lymphadenopathy. A lymph node larger than 1 cm that persists for 4 to 6 weeks should be considered suspicious and biopsied. Patients with diffuse NHL may present with cutaneous lesions, testicular masses, or solitary bone lesions. A number of grades of NHL are recognized. Therapy is dependent on the grade of the diseases and includes chemotherapy, bone marrow transplant, and radiation. Among the newest approaches to treating the disease is the use of monoclonal antibodies targeted to reduce the numbers of malignant B cells associated with the tumors. The first of these to be approved in the US is rituximab.

How it Works
Rituximab in a genetically engineered monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes. The antibody is composed of two heavy chains and two light chains of amino acids. This antibody is produced by mammalian cell culture and is purified by affinity ion exchange. The purification process includes steps to ensure viral inactivation and removal.

Rituximab binds to the CD20 antigen, which is found on pre-B and mature B lymphocytes. This antigen is found on more than 90% of B-cells in NHL, but is not found on stem cells, pro-B cells, normal plasma cells, or other normal tissue. CD20 is important because it regulates early steps in the activation process for cell cycle initiation and differentiation. Free CD20 is not found in the circulation. Once rituximab binds to the CD20 antigen on B-lymphocytes, lysis of the B cell occurs. This lysis may be complement-mediated. Although the drug has been found to bind to normal lymphoid tissue in the thymus, the white pulp of the spleen, and a majority of B-lymphocytes in peripheral blood and lymph nodes, little or no binding has been observed in non-lymphoid tissues.

Clinical Tips
Rituximab is administered intravenously. It has a long half-life (about 60 hours) after the first infusion, lengthening to 174 after the fourth infusion. Administration of rituximab results in rapid and sustained depletion of circulating and tissue-based B cells. Among the 166 patients in a pivotal study of the drug, circulating B cells were depleted within the first three doses with sustained depletion for up to 6 to 9 months after treatment in 83% of patients. In addition, patients experience significant sustained reductions in IgM and IgG for up to 11 months after treatment. B-cell recovery generally begins about 6 months following completion of treatment.

Because of the nature of the disease in question, only a small number of patients (about 300) have been enrolled in studies in support of the safety and effectiveness of the drug. Among these, 87% of patients experienced an adverse event during therapy, the most common of which were fever, chills, weakness, headache, nausea, leukopenia and angioedema. Although immunoglobulins are decreased during rituximab therapy, the incidence of infection does not appear to increase. The incidence of adverse events does not appear to change following retreatment.

The recommended dose of rituximab is administered as an IV infusion once weekly for four doses (days 1, 8, 15, and 22) and can be given in the outpatient setting. IT SHOULD NEVER BE GIVEN AS AN IV PUSH OR BOLUS, but must be diluted according to directions.

What The Patient Should Know
Hypersensitivity reactions may occur, and the manufacturer recommends premedication with acetaminophen and diphenhydramine before each infusion.

References

  1. Press OW, Applebaum F, Ledbetter JA, et al. Monoclonal antibody 1F5 (anti-CD20) serotherapy of human B-cell lymphomas. Blood. 1987;69:584-591.

  2. Reff ME, Carner C, Chambers KS, et al. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood. 1994;83:435-445.

  3. Maloney DG, Liles TM, Czerwinski C, et al. Phase I clinical trial using escalating single- dose infusion of chimeric anti-CD20 monoclonal antibody (IDEC-C2B8) in patients with recurrent B-cell lymphoma. Blood. 1994;84:2457-2466.

  4. Maloney DG, Grillo-Lopez AJ, Bodkin D, et al. IDEC-C2B8: Results of a phase I multiple-dose trial in patients with relapsed non-Hodgkins's lymphoma. J Clin Oncol. 1997;15:3266-3274.

  5. Maloney DG, Grillo-Lopesz AJ, White CA, et al. IDEC-C2B8 (rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin's lymphoma. Blood. 1997;90:2188-2195.

1997 VirSci Corporation. All rights reserved.
As seen on PharmInfoNet (http://pharminfo.com)

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----- Original Message -----
From: elray
To: mol-cancer@lists.meds.com
Sent: Friday, April 28, 2000 2:26 PM
Subject: [MOL] rituxin

I'm looking for some information regarding treatment of non hodgkins with no chemo but with rituxin (perhaps two cycles, once a week for 8 weeks)  I heard it is quite effective.  What can you tell me.  I haven't had anmy treatment yet but my blood counts are decreasing and it might be time for some action.  Feed back please.  catch me at elray@gateway.net
 
thanks, roger

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