I-131 Tositumomab Produces Anti-Cancer Responses in Refractory NHL

I-131 Tositumomab Produces Anti-Cancer Responses in Refractory Non-Hodgkin’s Lymphoma

According to results recently published in the Journal of Clinical Oncology, Iodine I-131 tositumomab appears to produce significant anti-cancer activity in patients with low grade, non-Hodgkin’s lymphoma that has stopped responding to chemotherapy.

NHL is a form of cancer that begins in the cells of the lymph system. The lymph system includes the spleen, thymus, tonsils, bone marrow, lymph nodes and circulating immune cells. The main cells in the lymph system are lymphocytes, of which there are two types: B and T-cells. Each of these cells has a very specific function in aiding the body to fight infection. NHL is characterized by the excessive accumulation of atypical (cancerous) lymphocytes. These lymphocytes can crowd the lymph system and suppress the formation and function of other immune and blood cells. While NHL is categorized by the type of lymphocyte it involves, it is also further defined by the rate at which the cancer grows, based on the appearance of the cells under a microscope. High grade or aggressive NHL is the fastest growing and low grade or indolent lymphoma is the slowest growing. Transformed NHL refers to the disease course of cancer when it changes from a slower growing cancer to a faster growing cancer.

Treatment options for low grade NHL may include: no therapy until symptoms appear, radiation therapy, chemotherapy or newer biologic therapies that utilize the body’s immune system to fight cancer. Following initial treatment, most patients will have improved symptoms and a partial or complete disappearance of the lymphoma. However, most patients with low grade NHL ultimately experience a recurrence. Once patients stop responding to chemotherapy, they are referred to as refractory and are left with few treatment options.

I-131 Tositumomab is a type of biological therapy that is still being evaluated in clinical trials for the treatment of NHL. This type of treatment uses two separate strategies to target and kill cancer cells. I-131 is a radioactive substance that is linked to tositumomab, a monoclonal antibody. Monoclonal antibodies are proteins that can be produced in a laboratory and are able to identify specific antigens (proteins) on the surface of certain cells and bind to them. This binding stimulates the immune system to attack and kill the cancerous B-cells. Tositumomab binds to antigens found only on the surface of cancerous B-cells. This binding stimulates the immune system to attack the cancer cells in the same way a virus or bacteria is attacked. I-131 is a radioactive isotope that spontaneously emits radiation. When tositumomab binds to cancer cells, the attached I-131 additionally destroys these cells by emission of its radiation. This type of treatment not only provides two separate treatment strategies, but also allows the delivery of greater amounts of radiation to the cancer cells while minimizing radiation exposure to normal cells.

Recently, a multi-institutional clinical trial was conducted to further evaluate treatment with one course of I-131 tositumomab in 60 patients with refractory low grade or transformed low grade NHL. The patients in this trial had received an average of 4 prior chemotherapy regimens. Results from treatment with I-131 tositumomab were compared to those from the patient’s last chemotherapy regimen. A partial or complete disappearance of cancer occurred in 65% of patients following treatment with I-131 tositumomab, compared with only 28% of patients following their last chemotherapy regimen. The average duration of an anti-cancer response was 6.5 months after I-131 tositumomab compared with only 3.4 months following chemotherapy. Twenty percent of patients achieved a complete disappearance of their cancer after I-131 tositumomab, with sustained responses not yet reached 47 months after treatment. Only 3% of patients achieved a complete disappearance of their cancer following their last chemotherapy regimen, with a sustained response of only 6.1 months. Side effects following treatment with I-131 tositumomab were generally well-tolerated, with only one patient being hospitalized for neutropenia (low white blood levels).

These results are very encouraging for patients with low grade NHL who have stopped responding to chemotherapy, as these patients are left with very few treatment options. I-131 tositumomab is in the later phases of clinical trials and may present a promising treatment option for NHL patients earlier in the course of their disease either alone or in combination with other treatment modalities. Patients with NHL may wish to speak with their physician about the risks and benefits of participating in a clinical trial further evaluating I-131 tositumomab or other promising therapeutic approaches. Two sources of information regarding ongoing clinical trials include comprehensive, easy-to-use listing services provided by the National Cancer Institute (cancer.gov) or eCancerTrials.com. eCancerTrials.com also provides personalized clinical trial searches on behalf of patients. (Journal of Clinical Oncology, Vol 19, Issue 19, pp 3918-3928, 2001)

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