ZevalinÔ (Ibritumomab tiuxetan) is a radiolabeled monoclonal antibody for B-cell lymphomas - the first to be approved for human use by the US Food and Drug Administration (US FDA approval granted February 19, 2002). It is manufactured in the US by IDEC Pharmaceuticals. It is licensed to Schering AG, Germany for worldwide marketing & distribution outside the US. Schering received European approval for Zevalin® on January 22, 2004.
How it works: Radioimmunotherapy
Radioimmunotherapy is a promising new area of cancer treatment that combines the targeting power of monoclonal antibodies with the cell-damaging ability of localized radiation. Radioimmunotherapies like Zevalin are made by linking monoclonal antibodies – engineered in a laboratory to recognize and attach to substances on the surface of certain cells – to radioactive isotopes. When infused into a patient, these radiation-carrying antibodies circulate in the body until they locate and bind to the surface of specific cells, and then deliver their cytotoxic radiation directly to the cancerous cells.
Zevalin comes with two types of radiolabeling: One with Indium-111 (In-111) and one with Yttrium-90 (Y-90). Both are used in conjunction with Rituxan in a treatment plan.
Response
Zevalin received two separate approvals, a full approval and an accelerated approval, based on two major efficacy studies in the U.S. Determination of the effectiveness of the Zevalin therapeutic regimen in a relapsed or refractory patient population was based on overall response rates (ORR).
The first efficacy study, on which the full approval is based, was conducted in 54 patients with relapsed follicular lymphoma who no longer adequately responded to Rituxan, 74 percent showed an ORR to treatment with Zevalin, with 15 percent of patients achieving a complete remission (CR) to therapy, according to the International Workshop Response Criteria (IWRC).
The second study, a Phase III randomized, controlled trial, which supports accelerated approval, was conducted in 143 patients with relapsed or refractory, low grade or follicular NHL or transformed B-cell NHL. The 73 patients who received the Zevalin therapeutic regimen showed an ORR of 80 percent, compared to 56 percent in 70 patients who received Rituxan alone, according to the IWRC. Thirty percent (30%) of Zevalin patients achieved a complete remission (CR) and four percent (4%) achieved an unconfirmed complete remission (CRu) to therapy, compared to sixteen percent (16%) of Rituxan patients who achieved a complete remission and four percent (4%) who achieved an unconfirmed complete remission, according to the IWRC.
Side Effects
The primary side effect associated with Zevalin during clinical trials was reduction in blood-cell counts as a result of myelosuppression (decreased blood-cell production by the bone marrow). Patients more likely to experience this were those with bone marrow involvement in lymphoma or with significant bone marrow damage from prior therapy. Decreased blood counts resulted in hospitalizations for infection or febrile neutropenia (a decrease in the number of neutrophils, a type of white blood cell that fights infection, in the blood) in 7 percent of patients, and life-threatening bleeding in less than 1 percent.
The non-hematologic (non-blood-related) side effects experienced by patients in the trials were generally mild and reversible. These side effects included infusion-related reactions, such as chills, fever, throat irritation and nausea, and are consistent with those seen with Rituxan (Rituximab monoclonal antibody) as single-agent therapy.
Severe infections (predominately bacterial in origin) and hemorrhage, including fatal cerebral hemorrhage, have occurred in a minority of patients in clinical studies. Also seen were myeloid malignancies and dyscrasias (myelodysplastic syndrome). The most common toxicities reported were neutropenia, thrombocytopenia, anemia, gastrointestinal symptoms (nausea, vomiting, abdominal pain, and diarrhea), increased cough, dyspnea, dizziness, arthralgia, anorexia and ecchymosis
Sponsored Links
Resources
Manufacturer / More Information:
US Official Product Site http://www.zevalin.com/
o US Zevalin Patient Information - Zevalin and Non-Hodgkin's Lymphoma
o IDEC Pharmaceuticals Corporation
3030 Callan Road
San Diego, CA 92121
Phone +1 (858) 431-8500 Fax +1 (858) 431-8750 http://www.biogenidec.com
o The company has a Patient Assistance Program to help patients with their insurance companies and for those with a demonstrated need
Outside the US Product Information
o Schering Press Release on European Approval (und auf Deutsch)
o The contact information for Schering is in the article above.
Multimedia Resources
Innovative Weapons in the War on Cancer: Monoclonal Antibodies – Video
Radiotherapy: Safety Measures During Therapy – Video
Smarter Drugs Deliver Radiation Directly to Lymphoma Cells - Video
Cancer Radiation Treatment From the Inside – Article
Cutting Edge Therapy: Monoclonal Antibody Treatment for Non-Hodgkin's Lymphoma – Article
Published Papers
• Horning, SJ Future directions in radioimmunotherapy for B-cell lymphoma, Semin Oncol. 2003 Dec;30(6 Suppl 17):29-34
• Gordon, LI Practical considerations and radiation safety in radioimmunotherapy with yttrium 90 ibritumomab tiuxetan (Zevalin), Semin Oncol. 2003 Dec;30(6 Suppl 17):23-8.
• Witzig, TE Efficacy and safety of 90Y ibritumomab tiuxetan (Zevalin) radioimmunotherapy for non-Hodgkin's lymphoma, Semin Oncol. 2003 Dec;30(6 Suppl 17):11-6.
• Hernandez MC, Knox SJ., Radiobiology of radioimmunotherapy with 90Y ibritumomab tiuxetan (Zevalin), Semin Oncol. 2003 Dec;30(6 Suppl 17):6-10.
• Forero A, Lobuglio AF, History of antibody therapy for non-Hodgkin's lymphoma, Semin Oncol. 2003 Dec;30(6 Suppl 17):1-5.
• More: Search PubMed for "Zevalin"
Other Material
A comparison of Zevalin and Bexxar
Zevalin information from Drugs.Com
Related Articles
For more information on Adult Non-Hodgkin's Lymphoma, please see the following pages:
Lymphoma Information Network: Monoclonal Antibodies
Lymphoma Information Network: Immunotherapy
Adult Non-Hodgkins Lymphoma: Chemotherapy
Adult Non-Hodgkin's Lymphoma: Treatment
Adult Non-Hodgkin's Lymphoma: Resources
Adult Non-Hodgkin's Lymphoma: Diagnosis
Lymphoma Classification and Types
Adult Non-Hodgkin's Lymphoma: Aggressive NHLs
Adult Non-Hodgkin's Lymphoma: Indolent NHLs
Adult Non-Hodgkin's Lymphoma: Introduction
Other pages you may want to visit:
Lymphoma Information Network
Childhood Non-Hodgkin's Information Pages
