Update on cancer therapeutics最新文献

{"title":"Plasma cell dyscrasias and leukemias","authors":"Peter H. Wiernik","doi":"10.1016/j.uct.2006.05.007","DOIUrl":"10.1016/j.uct.2006.05.007","url":null,"abstract":"<div><p><span>There has been remarkable progress in our understanding of plasma cell dyscrasias<span><span><span> and leukemias in recent years. New prognostic factors have come to light. Del(1)(p12) and t(4;14) confer poor prognoses on patients with </span>myeloma. COX-2 positivity is associated with poorer progression-free and overall survival in myeloma patients and a role for COX-2 inhibitors in myeloma has been suggested. </span>Thalidomide (400</span></span> <span>mg/day) and dexamethasone (20</span> <!-->mg/m²<span><span> daily for 4 days) has emerged as first-line treatment for myelomas. Serious toxicities have been recognized, however. The thalidomide derivative, </span>lenalidomide<span> may be more active and less toxic than the parent compound and may replace it. Lenolidomide is also highly active against 5q-syndrome. Bortezomib is at least as active as thalidomide and less toxic, and the two drugs are not cross-resistant. Although marrow transplantation was the standard of care for newly diagnosed myeloma patients, recent prospective randomized studies cast doubt on its role.</span></span></p><p><span><span><span>ZAP-70 and CD38<span> expression have major prognostic impact on outcome of chronic lymphocytic leukemia (CLL). The former may be a stronger predictor of the need for treatment than the presence of an unmutated IgV(H) gene. Although </span></span>fludarabine is highly active in CLL, it may be associated with a higher number of second malignancies than are other treatments. </span>Rituximab has major activity against CLL. However, at standard dose its effectiveness is limited by the fact that </span>CD20 density is relatively low on CLL cells and circulating CD20 binds a significant fraction of administered drug. Either combining rituximab with other agents, or giving it in mega doses, which are safe and highly effective, can overcome these impediments.</p><p><span>Imatinib has revolutionized the treatment of chronic phase </span>chronic myelocytic leukemia<span><span><span> (CML) and markedly decreased the number of allogeneic bone marrow transplants done for this neoplasm. However, the development of rapid resistance to the agent in </span>blast crisis of CML or Philadelphia chromosome-positive </span>acute lymphocytic leukemia<span><span> gives the agent only a minor role in those diseases. More effective tyrosine kinase inhibitors currently under development may prove to be more useful in </span>acute leukemias<span> with the Philadelphia chromosome.</span></span></span></p><p><span>Clofarabine is a successful new drug for </span>acute myeloid leukemias<span><span> of childhood and juvenile myelomonocytic leukemia<span>. Drugs such as gemtuzumab ozogamicin<span>, FLT3 inhibitors and farnesyl transferase inhibitors have been disappointing in acute leukemia. </span></span></span>Histone deacetylase<span> inhibition, especially in combination with proteasome inhibition, may be effective acute leukemia treatment.</","PeriodicalId":87487,"journal":{"name":"Update on cancer therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.uct.2006.05.007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"55737633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}