Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2011
Phase I trial of cixutumumab combined with temsirolimus in patients with advanced cancer.
Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 5 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
71 citing papers in PubMed, 5 syntheses or guidelines pooled it, 116 citations in OpenAlex.
- Assessment of Risk of Bias in Osteosarcoma and Ewing's Sarcoma Randomized Controlled Trials: A Systematic Review.Current oncology (Toronto, Ont.) · 2021Pooled it
- mTOR Inhibitors in Castration-Resistant Prostate Cancer: A Systematic Review.Targeted oncology · 2017Pooled it
- Adverse Events and Efficacy of Cixutumumab in Phase II Clinical Trials: A systematic Review and Meta-Analysis.Clinical drug investigation · 2017Pooled it
- Management of adrenocortical carcinoma: a consensus statement of the Italian Society of Endocrinology (SIE).Journal of endocrinological investigation · 2016Guideline
- The adverse events profile of anti-IGF-1R monoclonal antibodies in cancer therapy.British journal of clinical pharmacology · 2014Pooled it
- A parallel-arm phase I trial of the humanised anti-IGF-1R antibody dalotuzumab in combination with the AKT inhibitor MK-2206, the mTOR inhibitor ridaforolimus, or the NOTCH inhibitor MK-0752, in patients with advanced solid tumours.British journal of cancer · 2014Trial
- Trial
- IGF-1R inhibitors in cancer: A review of available evidence and future outlook.Critical reviews in oncology/hematology · 2025Review
- ERα/PR crosstalk is altered in the context of the ERα Y537S mutation and contributes to endocrine therapy-resistant tumor proliferation.NPJ breast cancer · 2023Article
- Insulin Receptor Isoforms and Insulin Growth Factor-like Receptors: Implications in Cell Signaling, Carcinogenesis, and Chemoresistance.International journal of molecular sciences · 2023Review
- Hyperglycemia and Glycemic Variability Associated with Glucocorticoids in Women without Pre-Existing Diabetes Undergoing Neoadjuvant or Adjuvant Taxane Chemotherapy for Early-Stage Breast Cancer.Journal of clinical medicine · 2023Article
- Altered expression of theInternational journal of oncology · 2022Article
- Review
- Targeting the IGF/PI3K/mTOR pathway and AXL/YAP1/TAZ pathways in primary bone cancer.Journal of bone oncology · 2022Article
- SIRT1 is involved in adrenocortical cancer growth and motility.Journal of cellular and molecular medicine · 2021Article
- A Phase I Trial of IGF-1R Inhibitor Cixutumumab and mTOR Inhibitor Temsirolimus in Metastatic Castration-resistant Prostate Cancer.Clinical genitourinary cancer · 2020Article
- Systematic analysis of breast atypical hyperplasia-associated hub genes and pathways based on text mining.European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) · 2019Article
- Targeting mTOR for cancer therapy.Journal of hematology & oncology · 2019Review
- microRNA-431 as a Chemosensitizer and Potentiator of Drug Activity in Adrenocortical Carcinoma.The oncologist · 2019Article
- Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
purposeMammalian target of rapamycin (mTOR) inhibitors mediate AKT activation through a type 1 insulin-like growth factor receptor (IGF-1R)-dependent mechanism. Combining the mTOR inhibitor temsirolimus with cixutumumab, a fully human immunoglobulin G1 monoclonal antibody directed against IGF-1R, was expected to enhance mTOR-targeted anticancer activity by modulating resistance to mTOR inhibition. The objectives of this phase I study were to evaluate the tolerability and activity of temsirolimus and cixutumumab. EXPERIMENTAL
designPatients in sequential cohorts ("3 + 3" design) received escalating doses of temsirolimus with cixutumumab weekly for 28 days. At the maximum tolerated dose (MTD), 21 patients were randomized into three separate drug sequence treatment groups for serial blood draws and 2[18F]fluoro-2-deoxy-d-glucose positron emission tomography combined with X-ray computed tomography (FDG-PET/CT) scans for pharmacodynamic analyses (PD).
resultsForty-two patients with advanced cancer (19 male/23 female, median age = 53, median number of prior therapies = 4) were enrolled. MTD was reached at cixutumumab, 6 mg/kg IV and temsirolimus, 25 mg IV. Dose-limiting toxicities included grade 3 mucositis, febrile neutropenia, and grade 4 thrombocytopenia. The most frequent toxicities were hypercholesterolemia, hypertriglyceridemia, hyperglycemia, thrombocytopenia, and mucositis. Tumor reduction was observed in 2 of 3 patients with Ewing's sarcoma and in 4 of 10 patients with adrenocortical carcinoma. PD data suggest that cixutumumab alone or combined with temsirolimus increased plasma IGF-1 and IGF binding protein 3. FDG-PET/CT showed the odds of achieving stable disease decreased by 58% (P = 0.1213) with a one-unit increase in absolute change of standard uptake value from baseline to day 3.
conclusionsTemsirolimus combined with cixutumumab was well tolerated. We are currently enrolling expansion cohorts at the MTD for Ewing's sarcoma and adrenocortical carcinoma.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.