Zevalin Therapeutic Regimen

The Zevalin"' (Ibritumomab tiuxetan) therapeutic regimen - targeted radioimmunotherapy for patients with relapsed or refractory low-grade, follicular or transformed B-cell non-Hodgkin's lymphoma ( NHL ), including patients with Rituximab-refractory follicular NHL .
Zevalin is a targeted treatment, using a murine (mouse) derived antibody (part of the immune system - Zevalin uses an IgGl kappa monoclonal antibody), which is directed against the CD20 antigen (a marker on the outside of a cell.) The CD20 antigen is found on the surface of both normal and malignant B-lymphocytes. This antibody agent is called Ibritumomab. The Ibritumomab is bound to tiuxetan, which can in turn be bound to yttrium-90 (Y-90) or indium- 11 1 (In-1 11). These are radioactive molecules that give off radiation locally. (Indium is lowdose used for pre-treatment scanning, while yttrium gives the actual treatment dose.) Thus, the Zevalin particle seeks out and binds to CD20 antigens, which are increased on the lymphoma cells. By doing this it is directly delivering its radiation to the lymphoma cells. Because of the energy of the radiation, it is able to treat not only the cell to which the Zevalin particle attaches, but also nearby malignant cells.

 
The combination of precision and power
Data on Zevalin's effectiveness in relapsed or refractory lymphoma is based on overall response rates. The exact effects of the Zevalin therapeutic regimen on survival are not yet known.
 
Proven antibody
Ibritumomab, a murine IgG1 kappa monoclonal antibody, is directed against the CD20 antigen, found on the surface of normal and malignant B lymphocytes Ibritumom is covalently bound to tiuxetan, a high affinity chelator for yttrium-90 (Y-90) or indium-111 (In-111)
  Crossfire effect
Y-90, a high energy,pure beta emitter,induces cellular damage in target and neighboring cells 90% of the emitted energy from Y-90 is absorbed within a mean pathlength of 5 mm, corresponding to 100-200 cell diameters
 
One week course of therapy

The entire Zevalin therapeutic regimen can be completed within 7 to 9 days and safely administered in an outpatient setting

 
Dosing of the Zevalin therapeutic regimen
Treatment Schema
IV infusion of Rituximab 250 mg/m2,
followed within 4 hours by IV Injection of In-111 Zevalin (5.0 mCi)
Hours 48-72 after IN-111 ZEVAILIN:Whole body gamma camera imaging to assess biodistribution; tumor may or may not be visualized.

Day 7-9 after In-111 Zevalin
Rituximab 250 mg/m2, IV,
followed within 4 hours
by Y-90 Zevalin (0.4 mCi/kg)
actual body weight
(maximum allowable dose 32.0mCi)

     

* Note that the dose of Rituximab is lower when used as part of the Zevalin therapeutic
regimen, as compared to the dose of Rituximab when used as a single agent. Rituximab is being used to block CD20 antigen on normal cells, so that the effect of Zevalin will more focused on malignant lymphoma cells.

*Dosing of Y-90 Zevalin is based on actual body weight and platelet count

* Y-90 Zevalin is not givin to patients if the biodistribution of In-111 Zevalin is not normal.

*Y-90 Zevalin is not givin to patients with a platelet count < 100,000/ mm 3

 
 
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