According to a recent article published in the journal Blood, results from the largest comparative trial evaluating initial chemotherapy regimens indicate that fludarabine may be the optimal choice for advanced chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is a cancer involving the lymph (immune) system, which includes lymph nodes, blood, and blood vessels found throughout the body, as well as the spleen, thymus, and tonsils. This cancer is found in large amounts in circulating blood and bone marrow (spongy material inside large bones that produces blood forming cells). Chronic lymphocytic leukemia is characterized by the production of atypical lymphocytes. Lymphocytes are specialized immune cells, of which there are two types: B and T-cells. These cells are produced in the bone marrow and each has a very specific function in aiding the body to fight infection. The large majority of CLL cases involve mature B-lymphocytes that tend to live much longer than normal, accumulating in the blood, bone marrow, lymph nodes and spleen. This results in overcrowding of these areas, suppressing the formation and function of blood and immune cells that are normally present. Additionally, the cancerous lymphocytes themselves do not function normally, leading to a further decrease in the ability of the body to fight infection. Chronic lymphocytic leukemia is considered to be a slow-growing, or low-grade cancer.

Standard treatment for CLL is chemotherapy, with the only known curative option being a stem cell transplant. The chemotherapy combination CHOP (cyclophosphamide, doxorubicin, oncovin and prednisone) has been a standard treatment regimen for many types of lymphoma. However, only a few clinical trials directly comparing CHOP to different chemotherapy options utilized for CLL have been conducted. This prompted researchers from the French Cooperative Group on CLL to conduct a clinical trial directly comparing CHOP, fludarabine and CAP (cyclophosphamide, doxorubicin and prednisone) in patients with previously untreated advanced CLL.

In this trial, over 900 patients received one of the 3 regimens as initial treatment. Overall, approximately 70% of patients achieved a partial or complete disappearance of their cancer. Of these patients, the average time to cancer progression following their initial therapy was 31.7 months for those treated with fludarabine, 29.5 months for those treated with CHOP and 27.7 months for those treated with CAP. Clinical remission rates based on molecular analysis were 40% for patients treated with fludarabine, 30% for patients treated with CHOP and 15.2% for patients treated with CAP. Fludarabine caused low platelet levels more frequently than CHOP or CAP, but resulted in fewer incidences of nausea/vomiting and hair loss than CHOP and CAP. The average survival times were similar between the 3 groups of patients; however, subsequent treatment regimens that were utilized following initial therapy hinders the ability to make direct comparisons in survival time between the 3 initial treatment regimens.

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Researchers conducting this trial suggest that the fludarabine should be considered as initial treatment for patients with CLL due to improved clinical responses and tolerability over CHOP or CAP, while CAP appeared to produce the least therapeutic benefits in this group of patients. Patients with CLL may wish to speak with their physician about the risks and benefits of these different chemotherapy combinations or the participation in a clinical trial evaluating novel therapeutic strategies. Two sources of ongoing information regarding clinical trials include comprehensive, easy-to-use listing services provided by the National Cancer Institute (cancer.gov) and eCancerTrials.com. eClinicalTrials.com also provides personalized clinical trial searches on behalf of patients. (Blood, Vol 98, No 8, pp 2319-2325, 2001)

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