ArticleAnnals of oncology : official journal of the European Society for Medical Oncology2013
Temsirolimus combined with sorafenib in hepatocellular carcinoma: a phase I dose-finding trial with pharmacokinetic and biomarker correlates.
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 34 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
34 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Pooled it
- Inefficiencies and Patient Burdens in the Development of the Targeted Cancer Drug Sorafenib: A Systematic Review.PLoS biology · 2017Pooled it
- Trial
- Trial
- A phase II trial of bevacizumab plus temsirolimus in patients with advanced hepatocellular carcinoma.Investigational new drugs · 2015Trial
- Prevalence of gastrointestinal side effects in hepatocellular carcinoma patients receiving sorafenib: a meta-analysis of 136 studies and 14,416 patients.Therapeutic advances in medical oncology · 2026Article
- mTOR Signaling: Roles in Hepatitis B Virus Infection and Hepatocellular Carcinoma.International journal of biological sciences · 2024Review
- Unraveling the Janus-Faced Role of Autophagy in Hepatocellular Carcinoma: Implications for Therapeutic Interventions.International journal of molecular sciences · 2023Review
- Mutant Kras and mTOR crosstalk drives hepatocellular carcinoma development via PEG3/STAT3/BEX2 signaling.Theranostics · 2022Article
- Phase II Trial of the Combination of Temsirolimus and Sorafenib in Advanced Hepatocellular Carcinoma with Tumor Mutation Profiling.Liver cancer · 2021Article
- Nephrotoxicity of Anti-Angiogenic Therapies.Diagnostics (Basel, Switzerland) · 2021Review
- Is the era of sorafenib over? A review of the literature.Therapeutic advances in medical oncology · 2020Review
- Article
- Clinical Pharmacokinetics and Pharmacodynamics of Transarterial Chemoembolization and Targeted Therapies in Hepatocellular Carcinoma.Clinical pharmacokinetics · 2019Review
- [Research advances in the mammalian target of rapamycin signaling pathway and its inhibitors in treatment of hepatocellular carcinoma].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2018Review
- Precision medicine for hepatocellular carcinoma: driver mutations and targeted therapy.Oncotarget · 2017Review
- Combination of Photon and Carbon Ion Irradiation with Targeted Therapy Substances Temsirolimus and Gemcitabine in Hepatocellular Carcinoma Cell Lines.Frontiers in oncology · 2017Article
- Combination treatment including targeted therapy for advanced hepatocellular carcinoma.Oncotarget · 2016Review
- Advanced Hepatocellular Cancer: the Current State of Future Research.Current treatment options in oncology · 2016Review
- Dosing de novo combinations of two targeted drugs: Towards a customized precision medicine approach to advanced cancers.Oncotarget · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors.
Funding
Abstract
backgroundBased upon preclinical evidence for improved antitumor activity in combination, this phase I study investigated the maximum-tolerated dose (MTD), safety, activity, pharmacokinetics (PK), and biomarkers of the mammalian target of rapamycin inhibitor, temsirolimus, combined with sorafenib in hepatocellular carcinoma (HCC). PATIENTS AND
methodsPatients with incurable HCC and Child Pugh score ≤B7 were treated with sorafenib plus temsirolimus by 3 + 3 design. The dose-limiting toxicity (DLT) interval was 28 days. The response was assessed every two cycles. PK of temsirolimus was measured in a cohort at MTD.
resultsTwenty-five patients were enrolled. The MTD was temsirolimus 10 mg weekly plus sorafenib 200 mg twice daily. Among 18 patients at MTD, DLT included grade 3 hand-foot skin reaction (HFSR) and grade 3 thrombocytopenia. Grade 3 or 4 related adverse events at MTD included hypophosphatemia (33%), infection (22%), thrombocytopenia (17%), HFSR (11%), and fatigue (11%). With sorafenib, temsirolimus clearance was more rapid (P < 0.05). Two patients (8%) had a confirmed partial response (PR); 15 (60%) had stable disease (SD). Alpha-fetoprotein (AFP) declined ≥50% in 60% assessable patients.
conclusionThe MTD of sorafenib plus temsirolimus in HCC was lower than in other tumor types. HCC-specific phase I studies are necessary. The observed efficacy warrants further study.
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Registered trials
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