ArticleInvestigational new drugs2017
A phase I dose-escalation study of Selumetinib in combination with Erlotinib or Temsirolimus in patients with advanced solid tumors.
Article in Investigational new drugs, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT00600496 (A Phase I, Open-Label, Multi-center Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD6244), which is not on this map. Cited by 12 papers, 1 of them a synthesis that pooled it.
What it found
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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.
A Phase I, Open-Label, Multi-center Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD6244 (ARRY-142886) When Given in Combination With Standard Doses of Selected Chemotherapies to Patients With Advanced Solid Tumors
Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Reporting on patient's body mass index (BMI) in recent clinical trials for patients with breast cancer: a systematic review.Breast cancer research : BCR · 2024Pooled it
- SARC031: A Phase II Trial of Selumetinib and Sirolimus for Patients with Unresectable or Metastatic Malignant Peripheral Nerve Sheath Tumors (MPNST).Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Selumetinib in Combination with Anti Retroviral Therapy in HIV-associated Kaposi sarcoma (SCART): an open-label, multicentre, phase I/II trial.BMC cancer · 2025Trial
- A Phase I Study of Dinaciclib in Combination With MK-2206 in Patients With Advanced Pancreatic Cancer.Clinical and translational science · 2020Trial
- Hypoxia-induced drug-resistance bias 3D cancer spheroid drug screens.APL bioengineering · 2026Article
- Molecular mechanisms underlying the action of carcinogens in gastric cancer with a glimpse into targeted therapy.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Targeting mTOR in the Context of Diet and Whole-body Metabolism.Endocrinology · 2022Review
- Therapy resistance: opportunities created by adaptive responses to targeted therapies in cancer.Nature reviews. Cancer · 2022Review
- Clinical Pharmacokinetics and Pharmacodynamics of Selumetinib.Clinical pharmacokinetics · 2021Review
- Activation of the IGF Axis in Thyroid Cancer: Implications for Tumorigenesis and Treatment.International journal of molecular sciences · 2019Review
- β-Catenin mRNA Silencing and MEK Inhibition Display Synergistic Efficacy in Preclinical Tumor Models.Molecular cancer therapeutics · 2018Article
- Combination MEK and mTOR inhibitor therapy is active in models of glioblastoma.Neuro-oncology advancesArticle
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 7 institutions in 2 countries.
Funding
Abstract
Background Combinations of molecularly targeted agents may provide optimal anti-tumor activity and improve clinical outcomes for patients with advanced cancers. Selumetinib (AZD6244, ARRY-142886) is an oral, potent and highly selective, allosteric inhibitor of MEK1/2, a component of the RAS/RAF/MEK/ERK pathway which is constitutively activated in many cancers. We investigated the safety, tolerability, and pharmacokinetics (PK) of selumetinib in combination with molecularly targeted drugs erlotinib or temsirolimus in patients with advanced solid tumors. Methods Two-part study: dose escalation, to determine the maximum tolerated dose (MTD) of selumetinib in combination with erlotinib 100 mg once daily (QD) or temsirolimus 25 mg once weekly, followed by dose expansion at the respective combination MTDs to further investigate safety and anti-tumor effects. Results 48 patients received selumetinib plus erlotinib and 32 patients received selumetinib plus temsirolimus. The MTD with erlotinib 100 mg QD was selumetinib 100 mg QD, with diarrhea being dose limiting. The most common all grade adverse events (AEs): diarrhea, rash, nausea, and fatigue. Four (8.3%) patients had ≥12 weeks stable disease. The MTD with temsirolimus 25 mg once weekly was selumetinib 50 mg twice daily (BID), with mucositis and neutropenia being dose limiting. The most commonly reported AEs: nausea, fatigue, diarrhea, and mucositis. Ten (31.3%) patients had ≥12 weeks stable disease. The combination PK profiles were comparable to previously observed monotherapy profiles. Conclusions MTDs were established for selumetinib in combination with erlotinib or temsirolimus. Overlapping toxicities prevented the escalation of selumetinib to its recommended phase II monotherapy dose of 75 mg BID.
trial registrationClinicalTrials.gov NCT00600496; registered 8 July 2009.
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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.