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The National Comprehensive Cancer Network recently updated its guidelines for Non-Hodgkin's Lymphoma to include new therapeutic options, as well as changes to diagnostic criteria and staging.
NHL has been one of the most rapidly increasing types of cancer in the past few decades, and it is estimated that more than 63,000 new cases of NHL will be diagnosed in the United States in 2007. The increase is only partly explained by the concomitant development of NHL in the setting of HIV infection. Although NHL can manifest as several different types, it is generally classified as either T-cell or B-cell NHL.
The more common type, B-cell NHL, includes Burkitt's lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, and mantle cell lymphoma. T-cell NHLs include mycosis fungoides, anaplastic large cell lymphoma, and precursor T-lymphoblastic lymphoma. Prognosis and treatment of NHL depend on the stage and type of disease.
Fortunately, however, CTCL patients now have a new treatment option available with the approval of Merck's vorinostat (Zolinza). Vorinostat is a member of a relatively new class of agents known as the histone deacetylase (HDAC) inhibitors, which modulate the expression of genes by causing an increase in histone acetylation and ultimately induce cancer cell death. Interestingly, the well-known antiepileptic drug valproic acid (VPA) has also been shown to be a class I selective HDAC inhibitor, and there have been some recent studies to evaluate its efficacy in chemotherapy regimens. Vorinostat was approved in 2006 for the treatment of cutaneous manifestations in patients with progressive, persistent, or recurrent CTCL.
"Vorinostat is a welcome addition to the treatment armamentarium for CTCL, and patients are pleased that they only need to take one dose by mouth daily," said Nermin Boles-Attia, pharmacy supervisor at The University Hospital in Newark, N.J. Healthcare practitioners should be aware that vorinostat can increase the risk of developing deep vein thrombosis and pulmonary embolism. In addition, severe thrombocytopenia and gastrointestinal bleeding have been reported with concomitant use of vorinostat and other HDAC inhibitors. Therefore, it is recommended that platelet counts be monitored every two weeks during the first two months of treatment with vorinostat.
Another change to the NHL guidelines is the addition of alemtuzumab (Campath, Genzyme), an anti-CD52 humanized monoclonal antibody, as a first-line therapy option for certain patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Specifically, patients with the 17-p mutation are eligible for first-line treatment with alemtuzumab, which is approved for the treatment of relapsed and refractory CLL.
For patients without the mutation, rituximab (Rituxan, Genentech/Biogen Idec) was added to first-line therapy options in combination with chlorambucil (Leukeran, GlaxoSmithKline), cyclophosphamide, or CVP (cyclophosphamide, vincristine, and prednisone). Fludarabine with or without rituximab is still considered appropriate for first-line therapy of CLL/SLL. Rituximab was also added as an option for relapsed or refractory diffuse large B-cell lymphoma when used as part of a combination regimen.
With regard to diagnostic testing, the NCCN panel recommended that hepatitis B testing be included as part of the "essential" workup obtained in all patients with B-cell lymphomas. This comes largely as a result of findings that patients with B-cell NHL, but not those with T-cell NHL, have a higher prevalence of hepatitis B virus infection when compared with those who have other cancers.
To view the updated NCCN NHL guidelines in their entirety, go to http://www.nccn.org/.