ArticleAnnals of oncology : official journal of the European Society for Medical Oncology2013
Phase I study of humanized monoclonal antibody AVE1642 directed against the type 1 insulin-like growth factor receptor (IGF-1R), administered in combination with anticancer therapies to patients with advanced solid tumors.
Article in Annals of oncology : official journal of the European Society for Medical Oncology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 3 of them syntheses that pooled it.
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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.
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Who cites it
30 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Neutropenia and docetaxel exposure in metastatic castration-resistant prostate cancer patients: A meta-analysis and evaluation of a clinical cohort.Cancer medicine · 2019Pooled it
- Introducing fluorescence guided surgery into orthopedic oncology: A systematic review of candidate protein targets for Ewing sarcoma.Journal of surgical oncology · 2018Pooled it
- Adverse Events and Efficacy of Cixutumumab in Phase II Clinical Trials: A systematic Review and Meta-Analysis.Clinical drug investigation · 2017Pooled 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
- Circulating levels of insulin-like growth factor I (IGF-I) and risk of multiple myeloma: An observational and Mendelian randomisation study.British journal of haematology · 2026Observational
- Drug discovery for chemotherapeutic resistance based on pathway-responsive gene sets and its application in breast cancer.Frontiers in bioinformatics · 2025Article
- Insulin Receptor Isoforms and Insulin Growth Factor-like Receptors: Implications in Cell Signaling, Carcinogenesis, and Chemoresistance.International journal of molecular sciences · 2023Review
- Article
- Advances in insulin-like growth factor biology and -directed cancer therapeutics.Advances in cancer research · 2020Review
- 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
- Ceritinib-Induced Regression of an Insulin-Like Growth Factor-Driven Neuroepithelial Brain Tumor.International journal of molecular sciences · 2019Article
- Activation of the IGF Axis in Thyroid Cancer: Implications for Tumorigenesis and Treatment.International journal of molecular sciences · 2019Review
- Exploiting Signaling Pathways and Immune Targets Beyond the Standard of Care for Ewing Sarcoma.Frontiers in oncology · 2019Review
- Targeting Insulin-Like Growth Factor-I and Extracellular Matrix Interactions in Melanoma Progression.Scientific reports · 2018Article
- Protein Tyrosine Signaling and its Potential Therapeutic Implications in Carcinogenesis.Current pharmaceutical design · 2017Review
- Unbalancing p53/Mdm2/IGF-1R axis by Mdm2 activation restrains the IGF-1-dependent invasive phenotype of skin melanoma.Oncogene · 2017Article
- Expressions of insulin-like growth factor receptor-1 and cezanne-1 in lung adenocarcinoma.Medical oncology (Northwood, London, England) · 2017Article
- Type I insulin-like growth factor receptor signaling in hematological malignancies.Oncotarget · 2017Review
- Targeted therapy for soft tissue sarcomas in adolescents and young adults.Adolescent health, medicine and therapeutics · 2017Review
- Clinical Observations and Molecular Variables of Primary Vascular Leiomyosarcoma.JAMA surgery · 2016Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
backgroundType 1 insulin-like growth factor receptor (IGF-1R) mediates resistance to chemotherapy and targeted agents. This study assessed the safety, pharmacokinetics (PK), and tolerability of humanized IGF-1R antibody AVE1642 with other cancer treatments. PATIENTS: Patients with advanced solid tumors received three weekly AVE1642 dosed at 6 mg/kg, chosen following previous study, with 75 (cohort A) or 100 mg/m(2) (B) docetaxel, 1250 mg/m(2) gemcitabine/100 mg erlotinib (C1), or 60 mg/m(2) doxorubicin (D1). Blood samples were assayed for PK, IGFs, and IGF-BP3.
resultsFifty-eight patients received 317 AVE1642 infusions. The commonest adverse events were diarrhea (37/58 patients), asthenia (34/58), nausea (30/58), and stomatitis (21/58). Dose-limiting toxic effects in cohorts C1 (diarrhea) and D1 (neutropenia) prompted addition of cohorts C2 (1000 mg/m(2) gemcitabine/75 mg erlotinib) and D2 (50 mg/m(2) doxorubicin). Grade 3-4 hyperglycemia (three cases) accompanied steroid premedication for docetaxel administration. No PK interactions were detected. There were three partial responses in cohorts B (melanoma) and C (leiomyosarcoma, two cases) and 22 stabilizations ≥12 weeks, giving a control rate of 25/57 (44%). On treatment IGF-II rose by 68 ± 25 ng/ml in patients discontinuing treatment <12 weeks, and fell by 55.5 ± 21 ng/ml with disease control (P < 0.001).
conclusionAVE1642 was tolerable with 75-100 mg/m(2) docetaxel and 1000 mg/m(2) gemcitabine/75 mg erlotinib, achieving durable disease control in 44%, with an association between IGF-II and response.
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