Margaret von Mehren

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Background:This retrospective pooled analysis assessed the effect of age on the efficacy and safety of trabectedin in young and elderly patients with recurrent advanced soft tissue sarcoma (STS).Methods:Data from 350 adults with STS treated in five phase II trials with trabectedin were divided in the younger (<60 years; n=267) and the older cohort (⩾60(More)
Most gastrointestinal stromal tumors (GISTs) possess a gainof-function mutation in c-KIT . Imatinib mesylate, a smallmolecule inhibitor against several receptor tyrosine kinases, including KIT, platelet-derived growth factor receptor-A, and BCR-ABL, has therapeutic benefit for GISTs both via KIT and via unknown mechanisms. Clinical evidence suggests that a(More)
Approximately 15% of gastrointestinal stromal tumors (GISTs) in adults and 85% in children lack mutations in KIT and PDGFRA and are known as wild-type GISTs. Wild-type GISTs from adults and children express high levels of insulin-like growth factor 1 receptor (IGF1R) and exhibit stable genomes compared to mutant GISTs. Pediatric wild-type GISTs, GISTs from(More)
The contemporary clinical landscape of gastrointestinal stromal tumor (GIST) has evolved rapidly over the past several years. Widely used treatment guidelines--from the European Society of Medical Oncology (ESMO) and the National Comprehensive Cancer Network--have recently been updated and represent the most up-to-date, comprehensive tools guiding the(More)
 The bispecific monoclonal antibody (bsmAb) 2B1, targeting the extracellular domain of c-erbB-2, the protein product of the HER-2/neu proto-oncogene, and FcγRIII (CD16), expressed by human natural killer cells, neutrophils and differentiated monocytes, mediates the specific cytotoxic activity of these effector cells to tumor cells. A group of 24 patients(More)
Toll-like receptors are potent activators of the innate immune system and generate signals leading to the initiation of the adaptive immune response that can be utilized for therapeutic purposes. We tested the hypothesis that combined treatment with a Toll-like receptor agonist and an antitumor monoclonal antibody is effective and induces host-protective(More)
Combination therapy with trabectedin and docetaxel was evaluated in patients with advanced malignancies. In this open-label phase 1 study, docetaxel (60 or 75 mg/m2; 1-h intravenous infusion) was given on day 1 of a 21-day cycle in combination with escalating doses of trabectedin (0.4–1.3 mg/m2 by 3-h intravenous infusion, 1 h after docetaxel) and(More)
Purpose: To study the safety, tolerability, and pharmacokinetics of the selective tyrosine kinase inhibitor nilotinib as a single agent or in combinationwith imatinib in patientswith advanced imatinib-resistant gastrointestinal stromal tumors. Experimental Design: A phase I intercohort dose-escalation trial was done in patients who received either (a)(More)
Purpose: To study the safety, tolerability, and pharmacokinetics of the selective tyrosine kinase inhibitor nilotinib as a single agent or in combinationwith imatinib in patientswith advanced imatinib-resistant gastrointestinal stromal tumors. Experimental Design: A phase I intercohort dose-escalation trial was done in patients who received either (a)(More)
Imatinib inhibits the KIT and PDGFR tyrosine kinases, resulting in its notable antitumor activity in gastrointestinal stromal tumor (GIST). We previously reported the early results of a multi-institutional prospective trial (RTOG 0132) using neoadjuvant/adjuvant imatinib either in primary resectable GIST or as a planned preoperative cytoreduction agent for(More)