ArticleEuropean journal of cancer (Oxford, England : 1990)2015
Results of a phase 1 trial combining ridaforolimus and MK-0752 in patients with advanced solid tumours.
Article in European journal of cancer (Oxford, England : 1990), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01295632 (Phase I Parallel Protocol of MK-8669), which is not on this map. Cited by 39 papers.
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.
Phase I Parallel Protocol of MK-8669 (Ridaforolimus) + MK-2206 and MK-8669 (Ridaforolimus) + MK-0752 Doublets (MK-MK) in Patients With Advanced Cancer
Who cites it
39 citing papers in PubMed.
- Head and neck squamous cell carcinoma: current and emerging therapeutic strategies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Emerging roles of Notch signaling in the tumor microenvironment of digestive system cancers.Frontiers in molecular biosciences · 2026Review
- Cancer stem cells: landscape, challenges and emerging therapeutic innovations.Signal transduction and targeted therapy · 2025Review
- Review
- Decoding the NRF2-NOTCH Crosstalk in Lung Cancer-An Update.Antioxidants (Basel, Switzerland) · 2025Review
- Structural basis of human γ-secretase inhibition by anticancer clinical compounds.Nature structural & molecular biology · 2025Article
- Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.Signal transduction and targeted therapy · 2024Review
- Clinical research progress of ridaforolimus (AP23573, MK8668) over the past decade: a systemic review.Frontiers in pharmacology · 2024Review
- A novel platelets-related gene signature for predicting prognosis, immune features and drug sensitivity in gastric cancer.Frontiers in immunology · 2024Article
- Oncofetal reprogramming in tumor development and progression: novel insights into cancer therapy.MedComm · 2023Review
- In vitro antineoplastic effects of MK0752 in HPV-positive head and neck squamous cell carcinoma.Journal of cancer research and clinical oncology · 2023Article
- Update on immune-based therapy strategies targeting cancer stem cells.Cancer medicine · 2023Review
- Review
- Combination Therapy as a Promising Way to Fight Oral Cancer.Pharmaceutics · 2023Review
- AL101, a gamma-secretase inhibitor, has potent antitumor activity against adenoid cystic carcinoma with activated NOTCH signaling.Cell death & disease · 2022Article
- Breast Cancer Metastasis: Mechanisms and Therapeutic Implications.International journal of molecular sciences · 2022Review
- Tumor microenvironment pathways: Cross regulation in breast cancer metastasis.Genes & diseases · 2022Review
- Heterogeneity of BCSCs contributes to the metastatic organotropism of breast cancer.Journal of experimental & clinical cancer research : CR · 2021Review
- Pharmacological Disruption of the Notch1 Transcriptional Complex Inhibits Tumor Growth by Selectively Targeting Cancer Stem Cells.Cancer research · 2021Article
- Anti-Tumor Effects of Carrimycin and Monomeric Isovalerylspiramycin I on Hepatocellular CarcinomaFrontiers in pharmacology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
Abstract
backgroundThe phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of rapamycin (PI3K-AKT-mTOR) signalling pathway is aberrantly activated in several cancers. Notch signalling maintains cell proliferation, growth and metabolism in part by driving the PI3K pathway. Combining the mTOR inhibitor ridaforolimus with the Notch inhibitor MK-0752 may increase blockade of the PI3K pathway.
methodsThis phase I dose-escalation study (NCT01295632) aimed to define the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of combination oral ridaforolimus (rising doses starting at 20 mg, 5 days/week) and oral MK-0752 (1800 mg once weekly) in patients with solid tumours. No intrapatient dose escalation was permitted.
resultsTwenty eight patients were treated on study. Ridaforolimus doses were escalated from 20 to 30 mg/day. Among 14 evaluable patients receiving ridaforolimus 20 mg, one DLT (grade 2 stomatitis, second episode) was reported. Among eight evaluable patients receiving ridaforolimus 30 mg, three DLTs were reported (one each grade 3 stomatitis, grade 3 diarrhoea, and grade 3 asthenia). The MTD was 20 mg daily ridaforolimus 5 days/week+1800 mg weekly MK-0752. The most common drug-related adverse events included stomatitis, diarrhoea, decreased appetite, hyperglycaemia, thrombocytopenia, asthenia and rash. Two of 15 (13%) patients with head and neck squamous cell carcinoma (HNSCC) had responses: one with complete response and one with partial response. In addition, one patient experienced stable disease ⩾6 months.
conclusionsCombined ridaforolimus and MK-0752 showed activity in HNSCC. However, a high number of adverse events were reported at the MTD, which would require careful management during future clinical development.
Indexed as
Identifiers
What OpenQuestion holds
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.