Evidence map›Paper›PMID 30128950›Full record

ArticleCancer chemotherapy and pharmacology2018

A phase I trial of topotecan plus tivantinib in patients with advanced solid tumors.

Stephen V Liu, Susan G Groshen, Karen Kelly, Karen L Reckamp, Chandra Belani, Timothy W Synold, Amir Goldkorn, Barbara J Gitlitz, Mihaela C Cristea, I-Yeh Gong and 6 more

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

Article in Cancer chemotherapy and pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.9field-weighted citation impact, top 23% 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

2 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. 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

16 authors at 5 institutions in 1 country.

Stephen V LiuLombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA. stephen.v.liu@gunet.georgetown.edu.ORCID 0000-0002-4852-3914
Susan G GroshenUniversity of Southern California, Keck School of Medicine, Los Angeles, CA, USA.
Karen KellyUniversity of California Davis Comprehensive Cancer Center, Sacramento, CA, USA.
Karen L ReckampCity of Hope Comprehensive Cancer Center, Duarte, CA, USA.
Chandra BelaniPenn State Cancer Institute, Hershey, PA, USA.
Timothy W SynoldCity of Hope Comprehensive Cancer Center, Duarte, CA, USA.
Amir GoldkornUniversity of Southern California, Keck School of Medicine, Los Angeles, CA, USA.
Barbara J GitlitzUniversity of Southern California, Keck School of Medicine, Los Angeles, CA, USA.
Mihaela C CristeaCity of Hope Comprehensive Cancer Center, Duarte, CA, USA.
I-Yeh GongUniversity of California Davis Comprehensive Cancer Center, Sacramento, CA, USA.
Thomas J SemradUniversity of California Davis Comprehensive Cancer Center, Sacramento, CA, USA.
Yucheng XuUniversity of Southern California, Keck School of Medicine, Los Angeles, CA, USA.
Tong XuUniversity of Southern California, Keck School of Medicine, Los Angeles, CA, USA.
Marianna KoczywasCity of Hope Comprehensive Cancer Center, Duarte, CA, USA.
David R GandaraUniversity of California Davis Comprehensive Cancer Center, Sacramento, CA, USA.
Edward M NewmanCity of Hope Comprehensive Cancer Center, Duarte, CA, USA.
City of Hope · USUniversity of Southern California · USUC Davis Comprehensive Cancer CenterGeorgetown University · USPenn State Milton S. Hershey Medical Center · US

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Fumito Ito · 1985 to 2026
$181.4M
Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI STANLEY R. HAMILTON · 1985 to 2026
$86.3M
Phase I Molecular and Clinical Pharmacodynamic Trials ETCTNUM1CA186717 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI A. Dimitrios Colevas, Alexey V. Danilov · 2014 to 2026
$19.8M
NCI NIH HHS P30 CA014089NCI NIH HHS P30 CA033572NCI NIH HHS UM1 CA186717
6 · The paper itself

Abstract

purposeTyrosine kinase inhibitors (TKI) that target MET signaling have shown promise in various types of cancer, including lung cancer. Combination strategies have been proposed and developed to increase their therapeutic index. Based on preclinical synergy between inhibition of MET and topoisomerase I, a phase I study was designed to explore the combination of topotecan with the MET TKI tivantinib.

methodsEligible patients with advanced solid malignancies for which there was no known effective treatment received topotecan at doses of 1.0-1.5 mg/m

resultsThe trial included 18 patients, 17 of whom received treatment. At the planned doses, the combination of topotecan and tivantinib was not tolerable due to thrombocytopenia and neutropenia. The addition of G-CSF to attenuate neutropenia did not improve tolerability. Greater tivantinib exposure, assessed through pharmacokinetic analysis, was associated with greater toxicity. No responses were seen. MET phosphorylation was feasible in CTC, but no changes were seen with therapy.

conclusionsThe combination of topotecan and oral tivantinib was not tolerable in this patient population.

Indexed as

NeutropeniaPyrrolidinonesQuinolinesThrombocytopeniaTopotecanAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsDrug MonitoringFemaleHumansMaleMiddle AgedNeoplasmsNeoplasm StagingProto-Oncogene Proteins c-metTreatment FailureAntineoplastic AgentsARQ 197Proto-Oncogene Proteins c-metPyrrolidinonesQuinolinesTopotecanARQ-197Circulating tumor cellsMET phosphorylationTivantinibTopotecan

Identifiers

PMID30128950
PMCPMC6342617
OpenAlexW2888455722

What OpenQuestion holds

Textmetadata
LicenceTDM
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.