Insulin growth factor receptor (IGF-1R) antibody cixutumumab combined with the mTOR inhibitor temsirolimus in patients with metastatic adrenocortical carcinoma

A. Naing, P. Lorusso, S. Fu, D. Hong, H. X. Chen, L. A. Doyle, A. T. Phan, M. A. Habra, R. Kurzrock

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

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.Conclusion:Cixutumumab combined with temsirolimus was well tolerated and >40% of patients achieved prolonged SD.

Original languageEnglish (US)
Pages (from-to)826-830
Number of pages5
JournalBritish Journal of Cancer
Volume108
Issue number4
DOIs
StatePublished - Mar 5 2013

Keywords

  • adrenocortical carcinoma
  • cixutumumab
  • IGF-1R pathway
  • mTOR pathway
  • phase I clinical trials

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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