Evidence map›Paper›PMID 37036756›Full record

ArticleOncotarget2023

A phase I trial of riluzole and sorafenib in patients with advanced solid tumors: CTEP #8850.

Kristen R Spencer, Daniella E Portal, Joseph Aisner, Mark N Stein, Jyoti Malhotra, Weichung Shih, Nancy Chan, Ann W Silk, Shridar Ganesan, Susan Goodin and 7 more

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

Article in Oncotarget, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

6 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Article
  3. Riluzole in Combination with mFOLFOX6 and Bevacizumab in Treating Patients with Metastatic Colorectal Cancer: A Phase I Clinical Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
    Article
  4. Article
  5. Review
  6. 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

17 authors at 4 institutions in 1 country.

Kristen R SpencerRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08903, USA.
Daniella E PortalRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08903, USA.
Joseph AisnerRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08903, USA.
Mark N SteinRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08903, USA.
Jyoti MalhotraRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08903, USA.
Weichung ShihRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08903, USA.
Nancy ChanRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08903, USA.
Ann W SilkRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08903, USA.
Shridar GanesanRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08903, USA.
Susan GoodinRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08903, USA.
Murugesan GounderRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08903, USA.
Hongxia LinRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08903, USA.
Jiadong LiRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08903, USA.
Robert CerchioSusan Lehman Cullman Laboratory for Cancer Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
Christina MarinaroSusan Lehman Cullman Laboratory for Cancer Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
Suzie ChenRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08903, USA.
Janice M MehnertDepartment of Medicine, New York University Grossman School of Medicine, Perlmutter Cancer Center of NYU Langone Health, NY 10016, USA.
Rutgers, The State University of New Jersey · USRutgers Cancer Institute · USJohnson University · USNew York University · US

Funding

TRANSCRIPTIONAL PROFILINGP30CA072720 · NCI · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI Tracie Saunders · 1997 to 2026
$94.5M
Combination Therapy that Targets Glutamate Signaling in MelanomaR01CA149627 · NCI · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI GOYDOS, JAMES S. · 2010 to 2014
$1.7M
Translational application of mouse models of melanoma brain metastasesI01BX003742 · VA · VA NEW JERSEY HEALTH CARE SYSTEM · PI CHEN, SUZIE · 2018 to 2024
–
BLRD Research Career Scientist Award ApplicationIK6BX006319 · VA · VA NEW JERSEY HEALTH CARE SYSTEM · PI CHEN, SUZIE · 2023 to 2025
–
BLRD VA I01 BX003742BLRD VA IK6 BX006319NCI NIH HHS P30 CA072720NCI NIH HHS R01 CA149627
6 · The paper itself

Abstract

backgroundOverexpression of metabotropic glutamate receptor 1 (GRM1) has been implicated in the pathogenesis of multiple cancers. Riluzole, an inhibitor of glutamate release, showed synergistic antitumor activity in combination with the multi-kinase inhibitor sorafenib in preclinical models. This phase I trial identified the toxicity profile, dose-limiting toxicities, maximum tolerated dose (MTD), and pharmacokinetic and pharmacodynamic properties of riluzole combined with sorafenib in patients with advanced cancers. PATIENTS AND

methodsPatients with refractory solid tumors were enrolled utilizing a 3+3 dose-escalation design. Riluzole was given at 100 mg PO BID in combination with sorafenib, beginning at 200 mg PO daily and escalating in 200 mg increments per level in 28-day cycles. Restaging evaluations were performed every 2 cycles.

results35 patients were enrolled over 4 dose levels. The MTD was declared at dose level 3 (riluzole: 100 mg PO BID; sorafenib: 400 mg AM/200 mg PM). Pharmacokinetic analyses did not reveal definitive evidence of drug-drug interactions. Consistent decreases in phospho-forms of ERK and AKT in tumor tissue analyses with accompanying decrease in GRM1 expression and increase in pro-apoptotic BIM suggest target engagement by the combination. Best responses included a partial response in 1 (2.9%) patient with pancreatic acinar cell carcinoma with a KANK4-RAF1 fusion, and stable disease in 11 (36%) patients.

conclusionCombination therapy with riluzole and sorafenib was safe and tolerable in patients with advanced solid tumors. The partial response in a patient with a RAF1 fusion suggests that further exploration in a genomically selected cohort may be warranted.

Indexed as

NeoplasmsPancreatic NeoplasmsAntineoplastic Combined Chemotherapy ProtocolsHumansMaximum Tolerated DoseNiacinamidePhenylurea CompoundsRiluzoleSorafenibNiacinamidePhenylurea CompoundsRiluzoleSorafenibclinical trialGRM1phase Iriluzolesorafenib

Identifiers

PMID37036756
PMCPMC10085060
OpenAlexW4362734529

What OpenQuestion holds

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Registered trials

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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.