Managed Care - July 2008 - (Page H5) FIGURE IPSS risk categories: patient distribution 39% 31% 22% Risk category Numeric score Low 0 Int-1 0.5–1.0 Int-2 1.5–2.0 Int=intermediate, IPSS=international prognostic scoring system. Source: Greenberg 1997 cently, the novel hypomethylating agents, decitabine (Dacogen) and azacitidine (Vidaza), and the immunomodulator lenalidomide (Revlimid) have been approved for use. Although these new agents represent therapeutic advances, their adoption may require clinicians to make more complicated treatment decisions when developing management strategies. The guidelines developed by the National Comprehensive Cancer Network (NCCN) provide a good framework for understanding the disease, are widely recognized as representing the standard of care, and are useful in their application. The NCCN panel of experts endorses the use of IPSS risk categories and recommends treatments according to whether patients are assigned to either the low/intermediate-1 risk or intermediate-2/high-risk group. The NCCN recommends that all patients in the first group receive supportive care in addition to any treatment with disease-modifying agents. In the higherrisk group, patients are further stratified, depending on whether they are candidates for intensive therapy. Candidates for intensive therapy are at high risk for developing acute leukemia, but are young enough and have a good enough performance status to endure chemotherapy regimens and possibly transplantation. If patients are not candidates for such aggressive treatment, they may be candidates for the hypomethylating agents recently approved for this patient population. The NCCN also strongly encourages interested patients to participate in clinical trials, which help to improve outcomes for all patients. ESAs. These agents often are an efficacious alternative to repeated RBC transfusions. As MDS evolves, refractory anemia, which occurs in a majority of patients, can re- sult in a steady decline in hemoglobin and long-term dependence on packed RBC transfusions. Such transfusion dependence has been associated with iron overload and heart and liver complications, which can significantly reduce patient survival. Although their use is not without risk (NCCN 2008), ESAs may reduce the need for transfusion, raise hemoglobin levels, and improve QoL for patients who respond to therapy. Until recently, perhaps the greatest drawback to the use of ESAs was the lack of proper criteria for determining the adequacy of an 8% erythroid response (ER). However, in 2000, an International Working Group (IWG) proposed standardized criteria for evaluating clinically significant responses in patients High with MDS; in addition to standardized meas≥2.5 ures of cytogenetic response and improvement in health-related QoL, the group proposed criteria for assessing hematologic improvement (Cheson 2000). The relevance of all IWG response criteria has been validated in clinical trials, and has gained acceptance both in research studies and clinical practice. The standardized criteria for determining ER also have — perhaps inadvertently — helped to confirm the usefulness of ESAs such as EPO. A systematic review of data from 21 studies of patients with MDS who were treated with EPO has been instrumental in obtaining support for the use of IWG criteria for ER (Moyo 2006). The studies were published between 1990 and 2005 and evaluated 895 patients. The primary aim of the review was to analyze study characteristics that affected ER rate and determine possible explanations for between- and within-study variations. Ten studies (combined 604 patients) used the IWG criteria to define ER and 11 studies (291 patients) used other definitions (Moyo 2006). The mean age of all patients was 70.6 years, and 45 percent were women. Mean baseline serum EPO levels and the proportion of patients with refractory anemia were comparable between studies; however, the proportion of transfusion-dependent patients at baseline was lower in the IWG studies compared with the non-IWG studies (36 percent versus 84 percent, respectively, P<.001). Overall, significantly higher ER rates occurred in studies that used IWG criteria. Among patients in the IWG studies who achieved an ER, 62 percent (188/305) achieved a major ER. Findings also were more consistent among the IWG criteria studies, suggesting that IWG criteria represent a more refined definition of ER and, in turn, use of the IWG criteria represents an improvement in the management of anemia. This meta-analysis that involved an elderly population who were significantly anemic also helped to confirm that treatment with EPO is most effective in patients SUPPLEMENT / HEMATOLOGIC CANCER 5
For optimal viewing of this digital publication, please enable JavaScript and then refresh the page. If you would like to try to load the digital publication without using Flash Player detection, please click here.