The DOI matches its Crossref record; 25 of the 26 references it cites were found in a registry or an index.
Insulin Growth Factor-Receptor (IGF-1R) Antibody Cixutumumab Combined with the mTOR Inhibitor Temsirolimus in Patients with Refractory Ewing's Sarcoma Family Tumors
Open accessAbstract
PURPOSE: Temsirolimus was combined with cixutumumab, a fully human IgG1 monoclonal antibody directed at the insulin growth factor-1 receptor (IGF-1R). EXPERIMENTAL DESIGN: 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. CONCLUSION: Cixutumumab combined with temsirolimus was well-tolerated and showed preliminary evidence of durable antitumor activity in heavily pretreated EWS family tumors.
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“In another study, cixutumab in combination with temsirolimus was evaluated in 10 patients with ACC. Stable disease in 4 patients, at a maximum lasting for greater than 8 months, was the best response (317).”
From Adrenocortical carcinoma (2014) · cites this paper as [317]
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“Despite a wealth of preclinical information and two recent clinical trials demonstrating marked tumor regression in a subset of patients with EWS treated with combined antagonists of the IGF-1R/mTOR pathway, we noted a surprising lackluster cellular response to IGF-1R antagonists in conventional 2D monolayer culture (…”
BackgroundSingh, P., Alex, J. M., & Bast, F. (2013) · Medical Oncology · doi:10.1007/s12032-013-0805-3 · Cited by 208
“A series of conventional drugs such as Temsirolimus were combined with cixutumumab, a fully human IgG1 monoclonal antibody intended to target IGF-1R resulted in antitumor activity against Ewing’s family tumors without side effects [133].”
BackgroundIGF-1R as an anti-cancer target--trials and tribulations
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Metadata
- Authors
- Naing, A., LoRusso, P., Fu, S., Hong, D. S., Anderson, P., Benjamin, R. S., Ludwig, J., Chen, H. X., Doyle, L. A., & Kurzrock, R.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Naing, Aung
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2012-04-30
- Volume
- 18
- Issue
- 9
- Pages
- 2625-2631
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC3875297
- OpenAlex
- W1991236371
- Cited by
- 205
- References
- 26
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 7 · 2023: 5 · 2022: 7 · 2021: 15 · 2020: 10 · 2019: 10 · 2018: 9 · 2017: 12 · 2016: 15 · 2015: 27 · 2014: 31 · 2013: 31 · 2012: 13
- FWCI
- 26.32
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (U01-CA62487, U01 CA 62461, R21-CA13763301A1, U01CA062487, R21CA137633, U01CA062461, P30CA016672)
- Topics
- Health Sciences › Medicine › Oncology › Sarcoma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Health Sciences › Medicine › Hematology › Acute Lymphoblastic Leukemia research
- Keywords
- cixutumumab, temsirolimus, mTOR inhibitors, Ewing sarcoma, desmoplastic small round cell tumor, refractory cancer, combination therapy, hyperglycemia, mucositis, thrombocytopenia, anticancer activity
- MeSH terms
- Adolescent, Adult, Antibodies, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Bone Neoplasms, Female, Humans, Male, Prognosis, Remission Induction, Sarcoma, Ewing, Cohort Studies, Receptor, IGF Type 1, Sirolimus, Young Adult, Desmoplastic Small Round Cell Tumor, TOR Serine-Threonine Kinases, Neoplasm Grading, Antibodies, Monoclonal, Humanized
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