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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1 retracted
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RetractedNew Guidelines to Evaluate the Response to Treatment in Solid Tumors
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SEER Cancer Statistics Review, 1975-2003
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mTOR Inhibition Induces Upstream Receptor Tyrosine Kinase Signaling and Activates Akt
O'Reilly, K. E., Rojo, F., She, Q.-B., Solit, D., Mills, G. B., Smith, D., Lane, H., Hofmann, F., Hicklin, D. J., Ludwig, D. L., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-2925 · Cited by 2,561
Rapamycin induces feedback activation of Akt signaling through an IGF-1R-dependent mechanism
Wan, X., Harkavy, B., Shen, N., Grohar, P. J., & Helman, L. J. (2006) · Oncogene · doi:10.1038/sj.onc.1209990 · Cited by 761
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“EWS–FLI can bind the IGFBP3 promoter and repress its activity, further supporting the role of IGF-1R signaling in this malignancy (19).”
Olmos, D., Postel-Vinay, S. C., Molife, L. R., Okuno, S. H., Schuetze, S. M., Paccagnella, M. L., Batzel, G. N., Yin, D., Pritchard‐Jones, K., Judson, I. R., et al. (2009) · The Lancet Oncology · doi:10.1016/s1470-2045(09)70354-7 · Cited by 339
Tolcher, A. W., Sarantopoulos, J., Patnaik, A., Papadopoulos, K. P., Lin, C., Rodon, J. A., Murphy, B. A., Roth, B. J., McCaffery, I., Gorski, K. S., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.23.6745 · Cited by 306
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Items 201–204 of 204
Yakoub, M. A., Saoud, C., Reed, D. R., Wexler, L., Slotkin, E. K., Tap, W. D., Hameed, M., & Antonescu, C. R. (2026) · JCO Precision Oncology · doi:10.1200/po-25-00909
Current Status and Progress of Targeted and Immunotherapy for DSRCT
Wei, T., Zhao, Q., & Li, Y. (2026) · Cancers · doi:10.3390/cancers18111711
“In another study [95], 3 patients with DSRCT received combination therapy with cixutumumab (anti-IGF1R antibody) and temsirolimus (mTOR inhibitor), resulting in durable PFS exceeding 5 months in 2 patients.”
Insulin-like growth factor receptor signaling in physiology and disease
Dilawar, M., Malik, A., Liao, J., Shen, P., Huang, Z., Zhang, P., Wang, J., Zhang, N., Nisar, M. F., & Chen, G. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-026-02843-w · Cited by 1
Que, Y., Xie, X., Xie, W., Zuo, Y., Chen, W., Xu, Z., Gong, C., & Li, X. (2026) · Journal of Orthopaedic Translation · doi:10.1016/j.jot.2026.101235
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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