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 language | English (US) |
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Pages (from-to) | 826-830 |
Number of pages | 5 |
Journal | British Journal of Cancer |
Volume | 108 |
Issue number | 4 |
DOIs | |
State | Published - Mar 5 2013 |
Keywords
- adrenocortical carcinoma
- cixutumumab
- IGF-1R pathway
- mTOR pathway
- phase I clinical trials
ASJC Scopus subject areas
- Cancer Research
- Oncology