title: Insulin growth factor-receptor (IGF-1R) antibody cixutumumab combined with the mTOR inhibitor temsirolimus in patients with refractory Ewing's sarcoma family tumors.
abstract: OBJECTIVE
  Temsirolimus was combined with cixutumumab, a fully human IgG1 monoclonal antibody directed at the insulin growth factor-1 receptor (IGF-1R).
  
  
  METHODS
  Patients received cixutumumab, 6 mg/kg i.v. weekly, and temsirolimus, 25 to 37.5 mg i.v. weekly (4-week cycles), with restaging after 8 weeks. Median follow-up was 8.9 months.
  
  
  RESULTS
  Twenty patients [17 with Ewing's sarcoma (EWS), 3 with desmoplastic small-round cell tumor (DSRCT)] were enrolled. Twelve patients (60%) were men with a median age of 24 years and six median prior systemic therapies in a metastatic setting. The most frequent toxicities were thrombocytopenia (85%), mucositis (80%), hypercholesterolemia (75%), hypertriglyceridemia (70%), and hyperglycemia (65%; mostly grade I-II). Seven of 20 patients (35%) achieved stable disease (SD) for more than 5 months or complete/partial (CR/PR) responses. Tumor regression of more than 20% (23%, 23%, 27%, 100%, 100%) occurred in five of 17 (29%) patients with EWS, and they remained on study for 8 to 27 months. One of six patients with EWS who previously developed resistance to a different IGF-1R inhibitor antibody achieved a CR. Four of the seven best responders developed grade III mucositis, myelosuppression, or hyperglycemia, which were controlled while maintaining drug dose.
  
  
  CONCLUSIONS
  Cixutumumab combined with temsirolimus was well-tolerated and showed preliminary evidence of durable antitumor activity in heavily pretreated EWS family tumors.
authors.affiliation: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. anaing@mdanderson.org
authors.forename: Aung
authors.initials: A
authors.lastname: Naing
authors.forename: Patricia
authors.initials: P
authors.lastname: LoRusso
authors.forename: Siqing
authors.initials: S
authors.lastname: Fu
authors.forename: David S
authors.initials: DS
authors.lastname: Hong
authors.forename: Pete
authors.initials: P
authors.lastname: Anderson
authors.forename: Robert S
authors.initials: RS
authors.lastname: Benjamin
authors.forename: Joseph
authors.initials: J
authors.lastname: Ludwig
authors.forename: Helen X
authors.initials: HX
authors.lastname: Chen
authors.forename: Laurence A
authors.initials: LA
authors.lastname: Doyle
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy*; D015331:Cohort Studies; D058405:Desmoplastic Small Round Cell Tumor / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D011379:Prognosis; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors*; D012074:Remission Induction; D012512:Sarcoma, Ewing / Q000188:drug therapy*; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C557414:cixutumumab; C401859:temsirolimus; C546842:MTOR protein, human; D017526:Receptor, IGF Type 1; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus