Zevalin was the first Radioimmunotherapy treatment to be approved in the USA, and other countries.
Zevalin and other radioimmunotherapy treatments combine the two potent cancer fighting strategies. First, they use an anti CD-20 monoclonal antibody to target and destroy the normal and cancerous lymphocytes. Second they add the additional power of a radioactive particle to zap nearby cells and thereby dramatically increase the destruction of the lymphoma cells. Most of the clinical trials that lead to approval of Zevalin clearly show an impressive response rate even for patients who were refractory to previous chemotherapy and/or Rituxan. Zevalin consists of the monoclonal antibody Ibritumomab (similar to Rituxan but with no human part). Then they use Tiuxetan to attach the radioactive Yttrium-90 particle. Thus the generic name for Zevalin is Ibritumomab Tiuxetan.
The beta emissions from the Yttrium-90 have a path length of about 5mm. This is longer than the 1mm path length of the Iodine-131 used with Bexxar. This longer length may make Zevalin more effective against larger tumours, but it also means more normal tissue may be affected.
Some of the Yttrium-90 is shed from the antibody. Yttrium-90 is primarily attracted to the bone.
Since Zevalin does not emit any gamma radiation the patient can go home immediately and does not need to avoid contact with other people. However some safety precautions should be observed, mostly due to some radiation being released with body fluids.
Bexxar on the other hand does emit gamma radiation and patients taking Bexxar must take precautions to avoid contact with other people for about a week after treatment. See the Bexxar page for more details.
Zevalin is administered in two steps as an outpatient.
The first dose is a dose of Rituxan but at a lower dose than usual. It is given at 250mg/m2 instead of the usual 375mg/m2. The primary purpose of this dose of Rituxan is to bind to sites in the peripheral blood and marrow and clean those up so that the Zevalin dose can go to the more important tumour sites.
Next may come the imagining dose of the antibody Ibritumomab but with Indium-111 attached instead of Yttrium-90. Originally this dose was designed to allow imaging studies to determine the proper dose. This is because Yttrium only emits beta radiation but does not emit gamma radiation. Beta radiation cannot be imaged on scanners. Using Indium which emits gamma radiation allowed for imaging studies to determine where the Zevalin was going and what the optimal dose would be. Recent data shows that the dose appears to be consistent for all patients and is therefore based on patient weight and platelet count.
In Canada the Indium step is skipped since it is not required. The United States FDA announced in November 2011 the Indium step will be eliminated. This will make the treatment much more convenient for the patient, and help reduce the cost as well.
In Switzerland and Japan the Indium dose may still be given and one or more imaging scans may be performed over the next 2-9 days to verify that the biodistribution of Zevalin is as expected.
Recently a study has been published showing that the Indium stem has no value and can be safely eliminated.
Discriminatory power of the 111-indium scan (111-In) in the prediction of altered biodistribution of radio-immunoconjugate in the 90-yttrium ibritumomab tiuxetan therapeutic regimen: Meta-analysis of five clinical trials and 9 years of post-approval safety data
The therapeutic dose of Zevalin. Once again they give you a dose of Rituxan just as with step 1. Then they follow that with the therapeutic dose of Zevalin (Yttrium-90 Ibritumomab Tiuxetan)
Below are some studies showing how effective Zevalin is, and some of the novel ways in which it is being used to improve disease outcomes.