Evidence map›Paper›PMID 35907014›Full record

ArticleCancer chemotherapy and pharmacology2022

A phase I dose escalation, dose expansion and pharmacokinetic trial of gemcitabine and alisertib in advanced solid tumors and pancreatic cancer.

Justin A Chen, Jasmine C Huynh, Chun-Yi Wu, Ai-Ming Yu, Karen Matsukuma, Thomas J Semrad, David R Gandara, Tianhong Li, Jonathan W Riess, Kit Tam and 5 more

Open access · hybridAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer chemotherapy and pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.8field-weighted citation impact, top 33% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 7 citations in OpenAlex.

  1. Review
  2. The two sides of chromosomal instability: drivers and brakes in cancer.Signal transduction and targeted therapy · 2024
    Review
  3. Article
  4. 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

15 authors at 3 institutions in 1 country.

Justin A ChenDivision of Hematology and Oncology, Davis Comprehensive Cancer Center, University of California, 4501 X Street, Suite 3016, Sacramento, CA, 95817, USA.
Jasmine C HuynhDivision of Hematology and Oncology, Davis Comprehensive Cancer Center, University of California, 4501 X Street, Suite 3016, Sacramento, CA, 95817, USA.
Chun-Yi WuBioanalysis and Pharmacokinetics Core Facility, University of California, Sacramento, CA, 95817, USA.
Ai-Ming YuDepartment of Biochemistry and Molecular Medicine, University of California, Sacramento, CA, 95817, USA.
Karen MatsukumaDepartment of Pathology and Laboratory Medicine, University of California, Sacramento, CA, 95817, USA.
Thomas J SemradGene Upshaw Memorial Tahoe Forest Cancer Center, Truckee, CA, 96161, USA.
David R GandaraDivision of Hematology and Oncology, Davis Comprehensive Cancer Center, University of California, 4501 X Street, Suite 3016, Sacramento, CA, 95817, USA.
Tianhong LiDivision of Hematology and Oncology, Davis Comprehensive Cancer Center, University of California, 4501 X Street, Suite 3016, Sacramento, CA, 95817, USA.
Jonathan W RiessDivision of Hematology and Oncology, Davis Comprehensive Cancer Center, University of California, 4501 X Street, Suite 3016, Sacramento, CA, 95817, USA.
Kit TamDivision of Hematology and Oncology, Davis Comprehensive Cancer Center, University of California, 4501 X Street, Suite 3016, Sacramento, CA, 95817, USA.
Philip C MackDivision of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Anthony MartinezOffice of Clinical Research, Davis Comprehensive Cancer Center, University of California, Sacramento, CA, 95817, USA.
Nichole MahaffeyOffice of Clinical Research, Davis Comprehensive Cancer Center, University of California, Sacramento, CA, 95817, USA.
Karen L KellyDivision of Hematology and Oncology, Davis Comprehensive Cancer Center, University of California, 4501 X Street, Suite 3016, Sacramento, CA, 95817, USA.
Edward J KimDivision of Hematology and Oncology, Davis Comprehensive Cancer Center, University of California, 4501 X Street, Suite 3016, Sacramento, CA, 95817, USA. jhkim@ucdavis.edu.ORCID 0000-0002-8660-7465
Icahn School of Medicine at Mount Sinai · USTahoe Forest Hospital · USUniversity of California, Davis · US

Funding

Staff InvestigatorsP30CA093373 · NCI · UNIVERSITY OF CALIFORNIA DAVIS · PI Gina M Dayton · 2002 to 2026
$84.9M
NCI NIH HHS P30 CA093373
6 · The paper itself

Abstract

purposeAurora Kinase A (AKA) inhibition with gemcitabine represents a potentially synergistic cancer treatment strategy via mitotic catastrophe. The feasibility, safety, and preliminary efficacy of alisertib (MLN8237), an oral AKA inhibitor, with gemcitabine was evaluated in this open-label phase I trial with dose escalation and expansion.

methodsKey inclusion criteria included advanced solid tumor with any number of prior chemotherapy regimens in the dose escalation phase, and advanced pancreatic adenocarcinoma with up to two prior chemotherapy regimens. Four dose levels (DLs 1-4) of alisertib (20, 30, 40, or 50 mg) were evaluated in 3 + 3 design with gemcitabine 1000 mg/m

resultsIn total, 21 subjects were treated in dose escalation and 5 subjects were treated in dose expansion at DL4. Dose-limiting toxicities were observed in 1 of 6 subjects each in DL3 and DL4. All subjects experienced treatment-related adverse events. Grade ≥ 3 treatment-related adverse events were observed in 73% of subjects, with neutropenia observed in 54%. Out of 22 subjects evaluable for response, 2 subjects (9%) had partial response and 14 subjects (64%) had stable disease. Median PFS was 4.1 months (95% CI 2.1-4.5). No significant changes in pharmacokinetic parameters for gemcitabine or its metabolite dFdU were observed with alisertib co-administration.

conclusionsThis trial established the recommended phase 2 dose of alisertib 50 mg to be combined with gemcitabine. Gemcitabine and alisertib are a feasible strategy with potential for disease control in multiple heavily pre-treated tumors, though gastrointestinal and hematologic toxicity was apparent.

Indexed as

AdenocarcinomaNeoplasmsPancreatic NeoplasmsAntineoplastic Combined Chemotherapy ProtocolsAzepinesDeoxycytidineGemcitabineHumansMaximum Tolerated DosePyrimidinesAzepinesDeoxycytidineGemcitabineMLN 8237PyrimidinesAlisertibAurora kinase aGemcitabinePharmacokineticsPhase I

Identifiers

PMID35907014
PMCPMC9402746
OpenAlexW4288684675

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.