Evidence map›Paper›PMID 37311055›Full record

ArticleThe oncologist2023

A Phase I Trial of Bevacizumab and Temsirolimus in Combination With Valproic Acid in Advanced Solid Tumors.

Blessie Elizabeth Nelson, Apostolia M Tsimberidou, Xueyao Fu, Siqing Fu, Vivek Subbiah, Anil K Sood, Jordi Rodon, Daniel D Karp, George Blumenschein, Scott Kopetz and 2 more

Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in The oncologist, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01552434 (A Phase I Trial of Bevacizumab, Temsirolimus Alone and in Combination With Valproic Acid, or Cetuximab in Patients With Advanced Malignancy and Other Indications), which is not on this map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.5field-weighted citation impact, top 17% of its field
1 · What the graph read from 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.

2 · The registry

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.

NCT01552434 phase1terminatednot on this map

A Phase I Trial of Bevacizumab, Temsirolimus Alone and in Combination With Valproic Acid, or Cetuximab in Patients With Advanced Malignancy and Other Indications

TypeinterventionalSponsorM.D. Anderson Cancer CenterRan2012 to 2026Enrolled154ConditionsAdvanced Malignant Neoplasm, Castleman Disease, Digestive System Carcinoma, Erdheim-Chester DiseaseArmsBevacizumab, Cetuximab, Laboratory Biomarker Analysis, Pharmacological Study, Temsirolimus
3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
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  7. Parotid Gland Tumors: Molecular Diagnostic Approaches.International journal of molecular sciences · 2024
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 1 institution in 1 country.

Blessie Elizabeth NelsonDepartment of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID 0000-0002-8227-638X
Apostolia M TsimberidouDepartment of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Xueyao FuDepartment of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Siqing FuDepartment of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Vivek SubbiahDepartment of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Anil K SoodDepartment of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jordi RodonDepartment of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Daniel D KarpDepartment of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
George BlumenscheinDepartment of Thoracic and Head and Neck Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
Scott KopetzDepartment of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID 0000-0001-9647-3416
Shubham PantDepartment of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Sarina A Piha-PaulDepartment of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID 0000-0001-9455-1660
The University of Texas MD Anderson Cancer Center · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
NCI NIH HHS P30 CA016672NIH HHS P30CA016672
6 · The paper itself

Abstract

backgroundPreclinical models suggest synergy between anti-angiogenesis therapy, mammalian target of rapamycin (mTOR), and histone deacetylase inhibitors to promote anticancer activity.

methodsThis phase I study enrolled 47 patients between April 2012 and 2018 and determined safety, maximum tolerated dose (MTD), and dose-limiting toxicities (DLTs) when combining bevacizumab, temsirolimus, and valproic acid in patients with advanced cancer.

resultsMedian age of enrolled patients was 56 years. Patients were heavily pretreated with a median of 4 lines of prior therapy. Forty-five patients (95.7%) experienced one or more treatment-related adverse events (TRAEs). Grade 3 TRAEs were lymphopenia (14.9%), thrombocytopenia (8.5%), and mucositis (6.4%). Grade 4 TRAEs included lymphopenia (2.1%) and CNS cerebrovascular ischemia (2.1%). Six patients developed DLTs across 10 dose levels with grade 3 infection, rash, mucositis, bowel perforation, elevated lipase, and grade 4 cerebrovascular ischemia. The MTD was dose level 9 (bevacizumab 5 mg/kg days 1 and 15 intravenously (IV) plus temsirolimus 25 mg days 1, 8, 15, and 22 IV and valproic acid 5 mg/kg on days 1-7 and 15-21 per orally (PO)). Objective response rate (ORR) was 7.9% with confirmed partial response (PRs) in 3 patients (one each in parotid gland, ovarian, and vaginal cancers). Stable disease (SD) ≥+6 months was seen in 5 patients (13.1%). Clinical benefit state (CBR: PR + SD ≥+6 months) was 21%.

conclusionCombination therapy with bevacizumab, temsirolimus, and valproic acid was feasible, but there were numerous toxicities, which will require careful management for future clinical development (ClinicalTrials.gov Identifier: NCT01552434).

Indexed as

LymphopeniaMucositisNeoplasmsThrombocytopeniaAntineoplastic Combined Chemotherapy ProtocolsBevacizumabFemaleHumansIschemiaMaximum Tolerated DoseMiddle AgedSirolimusValproic AcidBevacizumabSirolimustemsirolimusValproic Acidbevacizumabclinical trialHIF-1 alphahistone deacetylase inhibitorstemsirolimusvalproic acidvascular endothelial growth factor

Identifiers

PMID37311055
PMCPMC10712705
OpenAlexW4380537998

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

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.