title: Insulin growth factor receptor (IGF-1R) antibody cixutumumab combined with the mTOR inhibitor temsirolimus in patients with metastatic adrenocortical carcinoma.
abstract: BACKGROUND
  Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy without an available effective systemic chemotherapy. Insulin growth factor 2 (IGF-2) overexpression leading to the activation of the IGF-1 receptor (IGF-1R)/mammalian target of rapamycin (mTOR) pathway is well described in ACC. Cixutumumab, a fully human IgG1 monoclonal antibody directed at IGF-1R was combined with temsirolimus on the basis of preclinical data.
  
  
  METHODS
  Patients received cixutumumab, 3-6 mg kg(-1) intravenously (IV) weekly, and temsirolimus, 25-37.5 mg IV weekly (4-week cycles), with restaging after 8 weeks.
  
  
  RESULTS
  Twenty-six patients were enrolled (13 (50%) men); median age, 47 years; median number of prior therapies, 4. Five patients previously received an IGF-1R inhibitor and one, temsirolimus. The most frequent toxicities, at least possibly drug related, were grade 1-2 thrombocytopenia (38%), mucositis (58%), hypercholesterolaemia (31%), hypertriglyceridemia (35%), and hyperglycaemia (31%). In all, 11 of 26 patients (42%) achieved stable disease (SD) >6 months (duration range=6-21 months) with 3 of the 11 having received a prior IGF-1R inhibitor.
  
  
  CONCLUSIONS
  Cixutumumab combined with temsirolimus was well tolerated and >40% of patients achieved prolonged SD.
authors: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. anaing@mdanderson.org
authors: A
authors: A
authors: Naing
authors: P
authors: P
authors: Lorusso
authors: S
authors: S
authors: Fu
authors: D
authors: D
authors: Hong
authors: H X
authors: HX
authors: Chen
authors: L A
authors: LA
authors: Doyle
authors: A T
authors: AT
authors: Phan
authors: M A
authors: MA
authors: Habra
authors: R
authors: R
authors: Kurzrock
mesh_terms: D018268:Adrenocortical Carcinoma / Q000188:drug therapy; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives*; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C557414:cixutumumab; C401859:temsirolimus; D020123:Sirolimus