The non-Hodgkin’s lymphomas (NHL) are the fifth most common cause of cancer in men and women in the United States, and the fifth and sixth leading causes of cancer deaths, respectively. Approximately 54,000 new cases are projected to be diagnosed in the United States this year, 25% to 30% of which are indolent histologies, with the remainder being aggressive tumors.
After decades of limited progress in the therapy of these disorders, therapeutic paradigms have undergone a revolution. This monumental change is clearly the result of the availability of rituximab(Drug information on rituximab) (Rituxan), the first monoclonal antibody approved for the treatment of a human malignancy.[2,3] However, fewer than half of patients with follicular NHL respond to rituximab, and the median response duration is about 1 year. Potential means of improving on this level of activity may be afforded by the new generation of radioimmunoconjugates, notably ibritumomab tiuxetan (Zevalin), recently approved by the Food and Drug Administration (FDA), and tositumomab/iodine-131 tositumomab (Bexxar).[4,5]
Other cytokines, such as interleukin-12 (IL-12), may augment the effector cell mechanisms activated when rituximab binds to the lymphoma cells. Additional data suggest that bcl-2 antisense can potentiate the activity of rituximab.
Focus on Targeted Therapies
This month’s Patient Referral Resource in B-cell non-Hodgkin’s lymphomas makes a resounding point that the current direction of clinical research has moved beyond minor modifications of the dose and schedule of standard, nonspecific cytotoxic approaches. The current focus is on specific, targeted therapies. The rational development of new strategies that integrate multiple antibodies directed against different antigens, cytokines that enhance the activity of those antibodies, antisense compounds, and new chemotherapy drugs with unique mechanisms of action will hopefully increase our ability to cure these patients.
The Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatment and Diagnosis (DCTD) at the National Cancer Institute (NCI) sponsors a variety of trials for patients with newly diagnosed non-Hodgkin’s lymphoma using a wide range of agents and schedules. The list below includes approved and/or active clinical trials that are currently being sponsored by the CTEP for the treatment of non-Hodgkin’s lymphoma. Information about these studies can be obtained from the principal investigator or contacts listed for each trial or from Bruce Cheson, MD, at CTEP (ChesonB@ctep.nci.nih.gov), 301-496-2522.
Title: Randomized Trial of Patient-Specific Vaccination with
Conjugated Follicular Lymphoma-Derived Idiotype with Local GM-CSF in First
Protocol Number: NCI-00-C-0050, NCI-9900.v6
Participating Institutions: National Cancer Institute Medicine Branch, Moffitt Cancer Center and Research Institute, Northwestern University, Duke University Medical Center, University of Pennsylvania Cancer Center, Bellevue Hospital Center
Contact: Larry W. Kwak, MD, Bethesda, Maryland, (301) 846-1607; for a complete listing of study contacts, click here
Latest Information: http://www.cancer.gov/clinical_trials/
Title: Randomized Phase III Study in Low-Grade Lymphoma Comparing Cyclophosphamide(Drug information on cyclophosphamide)-Fludarabine to Standard Therapy Followed by Maintenance
Protocol Number: E1496
Participating Institutions: Eastern Cooperative Oncology Group, Cancer and Leukemia Group B
Contact: Jean McDonald, Coordinator, Brookline, Massachusetts, (617) 632-3610