Evidence map›Paper›PMID 25573239›Full record

Trial reportInternational journal of oncology2015

Favorable effect of the combination of vinorelbine and dihydropyrimidine dehydrogenase‑inhibitory fluoropyrimidine in EGFR‑mutated lung adenocarcinoma: retrospective and in vitro studies.

Hiroki Izumi, Hirokazu Touge, Tadashi Igishi, Haruhiko Makino, Shizuka Nishii-Ito, Miyako Takata, Hirofumi Nakazaki, Yasuto Ueda, Shingo Matsumoto, Masahiro Kodani and 7 more

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

Trial report in International journal of oncology, 2015. 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
–field-weighted citation impact, top 92% 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, 3 citations in OpenAlex.

  1. Article
  2. Article
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 2 institutions in 2 countries.

Hiroki IzumiDivision of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, Yonago, Tottori 683‑8504, Japan.
Hirokazu TougeDivision of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, Yonago, Tottori 683‑8504, Japan.
Tadashi IgishiDivision of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, Yonago, Tottori 683‑8504, Japan.
Haruhiko MakinoDivision of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, Yonago, Tottori 683‑8504, Japan.
Shizuka Nishii-ItoDivision of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, Yonago, Tottori 683‑8504, Japan.
Miyako TakataDivision of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, Yonago, Tottori 683‑8504, Japan.
Hirofumi NakazakiDivision of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, Yonago, Tottori 683‑8504, Japan.
Yasuto UedaDivision of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, Yonago, Tottori 683‑8504, Japan.
Shingo MatsumotoDivision of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, Yonago, Tottori 683‑8504, Japan.
Masahiro KodaniDivision of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, Yonago, Tottori 683‑8504, Japan.
Jun KuraiDivision of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, Yonago, Tottori 683‑8504, Japan.
Kenichi TakedaDivision of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, Yonago, Tottori 683‑8504, Japan.
Tomohiro SakamotoDivision of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, Yonago, Tottori 683‑8504, Japan.
Masaaki YanaiDivision of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, Yonago, Tottori 683‑8504, Japan.
Natsumi TanakaDivision of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, Yonago, Tottori 683‑8504, Japan.
Chaitanya S NirodiDepartment of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA.
Eiji ShimizuDivision of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, Yonago, Tottori 683‑8504, Japan.
Tottori University · JPUniversity of South Alabama · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Although cytotoxic chemotherapy is essential in epidermal growth factor receptor (EGFR)‑mutated non‑small cell lung cancer (NSCLC), it is unclear which regimen is most effective. We retrospectively compared the efficacy of standard platinum‑based chemotherapy with that of combination chemotherapy using vinorelbine (VNR) plus dihydropyrimidine dehydrogenase‑inhibitory fluoropyrimidine (DIF) in EGFR‑mutated lung adenocarcinomas, and we investigated a potential mechanism by which the combination chemotherapy of VNR + DIF was favorable in the treatment of EGFR‑mutated lung adenocarcinoma in vitro. In our retrospective analysis, the response rate and disease control rate afforded by the VNR + DIF treatment tended to be better than those by platinum‑based chemotherapy, and the progression‑free survival of the 24 VNR + DIF‑treated patients was significantly longer than that of the 15 platinum‑based chemotherapy patients. In EGFR‑mutated PC9 cells, VNR induced EGFR dephosphorylation at a clinically achievable concentration. 1BR3‑LR cells, a line of fibroblast cells transfected with a mutant EGFR construct, were completely resistant to gefitinib in the medium containing 10% fetal bovine serum (FBS), whereas the sensitivity of these cells to gefitinib was increased in 0.5% FBS‑containing medium. Similarly, the sensitivity of 1BR3‑LR cells to VNR was increased when they were cultured in low‑serum condition. In addition, sodium orthovanadate (Na3VO4) inhibited the EGFR dephosphorylation induced by VNR or gefitinib and suppressed the cell growth inhibition by these agents in PC9 cells. VNR and gefitinib showed synergistic cell growth inhibition in combination with 5‑fluorouracil (5‑FU) in PC9 cells. We propose that the EGFR dephosphorylation induced by VNR is related to cell growth inhibitory activity of VNR, and that this is one of the mechanisms of the synergistic effect of VNR + 5‑FU in EGFR‑mutated lung cancer cells. In conclusion, the combination chemotherapy of VNR + DIF may be a promising treatment for NSCLC patients with EGFR mutations.

Indexed as

AdenocarcinomaAdenocarcinoma of LungAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungCell Line, TumorDihydrouracil Dehydrogenase (NADP)Drug CombinationsErbB ReceptorsFemaleFluorouracilGefitinibHumansKaplan-Meier EstimateDihydrouracil Dehydrogenase (NADP)Drug CombinationsEGFR protein, humanErbB ReceptorsFluorouracilGefitinibOxonic AcidQuinazolinesS 1 (combination)TegafurVinblastineVinorelbine

Identifiers

PMID25573239
PMCPMC4324589
OpenAlexW2080519615

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.