title: Temsirolimus for the treatment of mantle cell lymphoma.
abstract: Although recent progress has been made in the treatment of mantle cell lymphoma (MCL) the majority of patients experience relapse and ultimately die of their disease. The translocation t(11;14) is a prerequisite for the diagnosis of MCL and results in overexpression of cyclin D1. Its protein translation is controlled by mTOR, a key element of the PI3K/Akt pathway, and mTOR constitutes an attractive therapeutic target. Temsirolimus, a specific inhibitor of mTOR, has been evaluated in two Phase II trials in patients with relapsed MCL, and promising response rates up to 40% were found. Subsequently, a randomized Phase III trial was initiated, in which superiority in remission induction and progression-free survival could be demonstrated for a regimen of temsirolimus 175 mg for 3 weeks, followed by a 75-mg weekly application in comparison with established agents. This adds temsirolimus to the therapeutic armamentarium for the treatment of MCL. Further developments target combination therapy in MCL and other lymphoid neoplasms.
authors.affiliation: Department of Hematology, Oncology and Pneumology, Universitätsmedizin der Johannes Gutenberg-Universität, K.ö.R, Langenbeckstrasse 1, Mainz, Germany. g.hess@3-med.klinik.uni-mainz.de
authors.forename: Georg
authors.initials: G
authors.lastname: Hess
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D019938:Cyclin D1 / Q000032:analysis* / Q000378:metabolism*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D055502:Secondary Prevention; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D047908:Intracellular Signaling Peptides and Proteins; D019938:Cyclin D1; C401859:temsirolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus