Everolimus in Diffuse Large B-Cell Lymphomas
Copyright policy )Everolimus in Diffuse Large B-Cell Lymphomas
Satisfactory treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL) is not currently available and novel therapies are needed. mTOR is an intracellular kinase that is part of an aberrantly activated pathway in DLBCL. Preclinical studies in DLBCL cell lines demonstrated that everolimus, an oral selective mTOR inhibitor, induces cell cycle arrest and is synergistic with rituximab. Phase I studies indicated 10 mg daily to be the best dosing of everolimus in DLBCL. A large Phase II study in relapsed/refractory DLBCL confirmed the substantial activity (overall response rate: 30%) and good tolerability of everolimus in DLBCL, with thrombocytopenia being the main toxicity. The combination of everolimus and rituximab showed encouraging results (objective response rate: 38%; complete response: 13%), without increasing toxicity. Combination studies of everolimus with novel agents or with immunochemotherapy are underway.
- University of Pavia Italy
- Policlinico San Matteo Fondazione Italy
- Università dell Insubria (Varese) Italy
- University of Insubria Italy
Cancer Research, Lymphoma, diffuse large B-cell lymphoma; everolimus; mTOR pathway; rapamycin analogs; Oncology; Cancer Research, diffuse large B-cell lymphoma, rapamycin analog, Drug Evaluation, Preclinical, Protein Kinase Inhibitor, 610, Antineoplastic Agents, Phase I as Topic, Antineoplastic Agent, Clinical Trials, Phase II as Topic, Antineoplastic Combined Chemotherapy Protocols, Large B-Cell, Animals, Humans, Clinical Trials, Sirolimu, Everolimus, Protein Kinase Inhibitors, Sirolimus, Antineoplastic Combined Chemotherapy Protocol, TOR Serine-Threonine Kinase, Clinical Trials, Phase I as Topic, Animal, Medicine (all), TOR Serine-Threonine Kinases, Phase II as Topic, everolimu, Diffuse, Preclinical, mTOR pathway, Treatment Outcome, Oncology, Drug Evaluation, Lymphoma, Large B-Cell, Diffuse, Human, Signal Transduction
Cancer Research, Lymphoma, diffuse large B-cell lymphoma; everolimus; mTOR pathway; rapamycin analogs; Oncology; Cancer Research, diffuse large B-cell lymphoma, rapamycin analog, Drug Evaluation, Preclinical, Protein Kinase Inhibitor, 610, Antineoplastic Agents, Phase I as Topic, Antineoplastic Agent, Clinical Trials, Phase II as Topic, Antineoplastic Combined Chemotherapy Protocols, Large B-Cell, Animals, Humans, Clinical Trials, Sirolimu, Everolimus, Protein Kinase Inhibitors, Sirolimus, Antineoplastic Combined Chemotherapy Protocol, TOR Serine-Threonine Kinase, Clinical Trials, Phase I as Topic, Animal, Medicine (all), TOR Serine-Threonine Kinases, Phase II as Topic, everolimu, Diffuse, Preclinical, mTOR pathway, Treatment Outcome, Oncology, Drug Evaluation, Lymphoma, Large B-Cell, Diffuse, Human, Signal Transduction
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