Evidence map›Paper›PMID 24821881›Full record

Trial reportJournal of clinical oncology : official journal of the American Society of Clinical Oncology2014

Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin is safe, effective, and efficient neoadjuvant treatment for muscle-invasive bladder cancer: results of a multicenter phase II study with molecular correlates of response and toxicity.

Elizabeth R Plimack, Jean H Hoffman-Censits, Rosalia Viterbo, Edouard J Trabulsi, Eric A Ross, Richard E Greenberg, David Y T Chen, Costas D Lallas, Yu-Ning Wong, Jianqing Lin and 10 more

3 registry-linked trialsOpen access · bronzeAbstract readClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 132 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
132citing papers in PubMed, 6 pooled it
23.2field-weighted citation impact, top 1% 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.

NCT01031420 phase2completednot on this map

Phase II Trial of Neoadjuvant Dose Dense MVAC in Muscle Invasive Bladder Cancer and High Risk Urothelial Carcinoma of the Upper Urinary Tract

TypeinterventionalSponsorFox Chase Cancer CenterRan2009 to 2013Enrolled54ConditionsMuscle Invasive Bladder Cancer, High Risk Urothelial Carcinoma of the Upper Urinary TractsArmssingle arm dose dense MVAC
NCT03498196 phase1 / phase2terminatednot on this mapstarted 2018, after this paper: background citation

A Window of Opportunity Trial: Avelumab in Non-metastatic Muscle Invasive Bladder Cancer (BL-AIR: Bladder Cancer-Avelumab for Invasive Resectable Disease)

TypeinterventionalSponsorBaylor College of MedicineRan2018 to 2019Enrolled1ConditionsBladder Cancer, Metastatic Bladder Cancer, Invasive Bladder CancerArmsAvelumab
NCT04047693 phase2unknown statusnot on this mapstarted 2019, after this paper: background citation

Efficacy and Safety of Neoadjuvant Chemotherapy With Dose Dense MVAC Followed by Radical Surgery in Patients With MIBC and Locally Advanced Urothelial Carcinoma of Bladder: Phase II, Single-arm Study

TypeinterventionalSponsorPusan National University Yangsan HospitalRan2019 to 2022Enrolled32ConditionsMuscle Invasive Bladder Cancer, Urothelial Carcinoma, Neoadjuvant ChemotherapyArmsdose dense MVAC with pegylated GCSF
3 · Its place in the literature

Who cites it

132 citing papers in PubMed, 6 syntheses or guidelines pooled it, 279 citations in OpenAlex.

  1. Guideline
  2. Pooled it
  3. Pooled it
  4. Guideline
  5. NCCN Guidelines Insights: Bladder Cancer, Version 2.2016.Journal of the National Comprehensive Cancer Network : JNCCN · 2016
    Guideline
  6. Pooled it
  7. Phase II Trial of Risk-Enabled Therapy After Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer (RETAIN 1).Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025
    Trial
  8. Trial
  9. Neoadjuvant Atezolizumab With Gemcitabine and Cisplatin in Patients With Muscle-Invasive Bladder Cancer: A Multicenter, Single-Arm, Phase II Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2022
    Trial
  10. Trial
  11. A Randomized Phase II Study of Coexpression Extrapolation (COXEN) with Neoadjuvant Chemotherapy for Bladder Cancer (SWOG S1314; NCT02177695).Clinical cancer research : an official journal of the American Association for Cancer Research · 2021
    Trial
  12. Trial
  13. Trial
  14. Multicenter Prospective Phase II Trial of Neoadjuvant Dose-Dense Gemcitabine Plus Cisplatin in Patients With Muscle-Invasive Bladder Cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2018
    Trial
  15. Trial
  16. Trial
  17. Trial
  18. Observational
  19. Article
  20. Review

72 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 1 institution in 1 country.

Elizabeth R PlimackElizabeth R. Plimack, Rosalia Viterbo, Eric A. Ross, Richard E. Greenberg, David Y.T. Chen, Yu-Ning Wong, Alexander Kutikov, Efrat Dotan, Essel Dulaimi, Reza Mehrazin, Robert G. Uzzo, and Gary R. Hudes, Fox Chase Cancer Center, Temple Health; Jean H. Hoffman-Censits, Edouard J. Trabulsi, Costas D. Lallas, Jianqing Lin, and William Kevin Kelly, Thomas Jefferson University Hospital, Philadelphia, PA; Timothy A. Brennan and Norma Palma, Foundation Medicine, Cambridge, MA; and Stephen A. Boorjian, Mayo Clinic, Rochester, MN. elizabeth.plimack@fccc.edu.
Jean H Hoffman-CensitsElizabeth R. Plimack, Rosalia Viterbo, Eric A. Ross, Richard E. Greenberg, David Y.T. Chen, Yu-Ning Wong, Alexander Kutikov, Efrat Dotan, Essel Dulaimi, Reza Mehrazin, Robert G. Uzzo, and Gary R. Hudes, Fox Chase Cancer Center, Temple Health; Jean H. Hoffman-Censits, Edouard J. Trabulsi, Costas D. Lallas, Jianqing Lin, and William Kevin Kelly, Thomas Jefferson University Hospital, Philadelphia, PA; Timothy A. Brennan and Norma Palma, Foundation Medicine, Cambridge, MA; and Stephen A. Boorjian, Mayo Clinic, Rochester, MN.
Rosalia ViterboElizabeth R. Plimack, Rosalia Viterbo, Eric A. Ross, Richard E. Greenberg, David Y.T. Chen, Yu-Ning Wong, Alexander Kutikov, Efrat Dotan, Essel Dulaimi, Reza Mehrazin, Robert G. Uzzo, and Gary R. Hudes, Fox Chase Cancer Center, Temple Health; Jean H. Hoffman-Censits, Edouard J. Trabulsi, Costas D. Lallas, Jianqing Lin, and William Kevin Kelly, Thomas Jefferson University Hospital, Philadelphia, PA; Timothy A. Brennan and Norma Palma, Foundation Medicine, Cambridge, MA; and Stephen A. Boorjian, Mayo Clinic, Rochester, MN.
Edouard J TrabulsiElizabeth R. Plimack, Rosalia Viterbo, Eric A. Ross, Richard E. Greenberg, David Y.T. Chen, Yu-Ning Wong, Alexander Kutikov, Efrat Dotan, Essel Dulaimi, Reza Mehrazin, Robert G. Uzzo, and Gary R. Hudes, Fox Chase Cancer Center, Temple Health; Jean H. Hoffman-Censits, Edouard J. Trabulsi, Costas D. Lallas, Jianqing Lin, and William Kevin Kelly, Thomas Jefferson University Hospital, Philadelphia, PA; Timothy A. Brennan and Norma Palma, Foundation Medicine, Cambridge, MA; and Stephen A. Boorjian, Mayo Clinic, Rochester, MN.
Eric A RossElizabeth R. Plimack, Rosalia Viterbo, Eric A. Ross, Richard E. Greenberg, David Y.T. Chen, Yu-Ning Wong, Alexander Kutikov, Efrat Dotan, Essel Dulaimi, Reza Mehrazin, Robert G. Uzzo, and Gary R. Hudes, Fox Chase Cancer Center, Temple Health; Jean H. Hoffman-Censits, Edouard J. Trabulsi, Costas D. Lallas, Jianqing Lin, and William Kevin Kelly, Thomas Jefferson University Hospital, Philadelphia, PA; Timothy A. Brennan and Norma Palma, Foundation Medicine, Cambridge, MA; and Stephen A. Boorjian, Mayo Clinic, Rochester, MN.
Richard E GreenbergElizabeth R. Plimack, Rosalia Viterbo, Eric A. Ross, Richard E. Greenberg, David Y.T. Chen, Yu-Ning Wong, Alexander Kutikov, Efrat Dotan, Essel Dulaimi, Reza Mehrazin, Robert G. Uzzo, and Gary R. Hudes, Fox Chase Cancer Center, Temple Health; Jean H. Hoffman-Censits, Edouard J. Trabulsi, Costas D. Lallas, Jianqing Lin, and William Kevin Kelly, Thomas Jefferson University Hospital, Philadelphia, PA; Timothy A. Brennan and Norma Palma, Foundation Medicine, Cambridge, MA; and Stephen A. Boorjian, Mayo Clinic, Rochester, MN.
David Y T ChenElizabeth R. Plimack, Rosalia Viterbo, Eric A. Ross, Richard E. Greenberg, David Y.T. Chen, Yu-Ning Wong, Alexander Kutikov, Efrat Dotan, Essel Dulaimi, Reza Mehrazin, Robert G. Uzzo, and Gary R. Hudes, Fox Chase Cancer Center, Temple Health; Jean H. Hoffman-Censits, Edouard J. Trabulsi, Costas D. Lallas, Jianqing Lin, and William Kevin Kelly, Thomas Jefferson University Hospital, Philadelphia, PA; Timothy A. Brennan and Norma Palma, Foundation Medicine, Cambridge, MA; and Stephen A. Boorjian, Mayo Clinic, Rochester, MN.
Costas D LallasElizabeth R. Plimack, Rosalia Viterbo, Eric A. Ross, Richard E. Greenberg, David Y.T. Chen, Yu-Ning Wong, Alexander Kutikov, Efrat Dotan, Essel Dulaimi, Reza Mehrazin, Robert G. Uzzo, and Gary R. Hudes, Fox Chase Cancer Center, Temple Health; Jean H. Hoffman-Censits, Edouard J. Trabulsi, Costas D. Lallas, Jianqing Lin, and William Kevin Kelly, Thomas Jefferson University Hospital, Philadelphia, PA; Timothy A. Brennan and Norma Palma, Foundation Medicine, Cambridge, MA; and Stephen A. Boorjian, Mayo Clinic, Rochester, MN.
Yu-Ning WongElizabeth R. Plimack, Rosalia Viterbo, Eric A. Ross, Richard E. Greenberg, David Y.T. Chen, Yu-Ning Wong, Alexander Kutikov, Efrat Dotan, Essel Dulaimi, Reza Mehrazin, Robert G. Uzzo, and Gary R. Hudes, Fox Chase Cancer Center, Temple Health; Jean H. Hoffman-Censits, Edouard J. Trabulsi, Costas D. Lallas, Jianqing Lin, and William Kevin Kelly, Thomas Jefferson University Hospital, Philadelphia, PA; Timothy A. Brennan and Norma Palma, Foundation Medicine, Cambridge, MA; and Stephen A. Boorjian, Mayo Clinic, Rochester, MN.
Jianqing LinElizabeth R. Plimack, Rosalia Viterbo, Eric A. Ross, Richard E. Greenberg, David Y.T. Chen, Yu-Ning Wong, Alexander Kutikov, Efrat Dotan, Essel Dulaimi, Reza Mehrazin, Robert G. Uzzo, and Gary R. Hudes, Fox Chase Cancer Center, Temple Health; Jean H. Hoffman-Censits, Edouard J. Trabulsi, Costas D. Lallas, Jianqing Lin, and William Kevin Kelly, Thomas Jefferson University Hospital, Philadelphia, PA; Timothy A. Brennan and Norma Palma, Foundation Medicine, Cambridge, MA; and Stephen A. Boorjian, Mayo Clinic, Rochester, MN.
Alexander KutikovElizabeth R. Plimack, Rosalia Viterbo, Eric A. Ross, Richard E. Greenberg, David Y.T. Chen, Yu-Ning Wong, Alexander Kutikov, Efrat Dotan, Essel Dulaimi, Reza Mehrazin, Robert G. Uzzo, and Gary R. Hudes, Fox Chase Cancer Center, Temple Health; Jean H. Hoffman-Censits, Edouard J. Trabulsi, Costas D. Lallas, Jianqing Lin, and William Kevin Kelly, Thomas Jefferson University Hospital, Philadelphia, PA; Timothy A. Brennan and Norma Palma, Foundation Medicine, Cambridge, MA; and Stephen A. Boorjian, Mayo Clinic, Rochester, MN.
Efrat DotanElizabeth R. Plimack, Rosalia Viterbo, Eric A. Ross, Richard E. Greenberg, David Y.T. Chen, Yu-Ning Wong, Alexander Kutikov, Efrat Dotan, Essel Dulaimi, Reza Mehrazin, Robert G. Uzzo, and Gary R. Hudes, Fox Chase Cancer Center, Temple Health; Jean H. Hoffman-Censits, Edouard J. Trabulsi, Costas D. Lallas, Jianqing Lin, and William Kevin Kelly, Thomas Jefferson University Hospital, Philadelphia, PA; Timothy A. Brennan and Norma Palma, Foundation Medicine, Cambridge, MA; and Stephen A. Boorjian, Mayo Clinic, Rochester, MN.
Timothy A BrennanElizabeth R. Plimack, Rosalia Viterbo, Eric A. Ross, Richard E. Greenberg, David Y.T. Chen, Yu-Ning Wong, Alexander Kutikov, Efrat Dotan, Essel Dulaimi, Reza Mehrazin, Robert G. Uzzo, and Gary R. Hudes, Fox Chase Cancer Center, Temple Health; Jean H. Hoffman-Censits, Edouard J. Trabulsi, Costas D. Lallas, Jianqing Lin, and William Kevin Kelly, Thomas Jefferson University Hospital, Philadelphia, PA; Timothy A. Brennan and Norma Palma, Foundation Medicine, Cambridge, MA; and Stephen A. Boorjian, Mayo Clinic, Rochester, MN.
Norma PalmaElizabeth R. Plimack, Rosalia Viterbo, Eric A. Ross, Richard E. Greenberg, David Y.T. Chen, Yu-Ning Wong, Alexander Kutikov, Efrat Dotan, Essel Dulaimi, Reza Mehrazin, Robert G. Uzzo, and Gary R. Hudes, Fox Chase Cancer Center, Temple Health; Jean H. Hoffman-Censits, Edouard J. Trabulsi, Costas D. Lallas, Jianqing Lin, and William Kevin Kelly, Thomas Jefferson University Hospital, Philadelphia, PA; Timothy A. Brennan and Norma Palma, Foundation Medicine, Cambridge, MA; and Stephen A. Boorjian, Mayo Clinic, Rochester, MN.
Essel DulaimiElizabeth R. Plimack, Rosalia Viterbo, Eric A. Ross, Richard E. Greenberg, David Y.T. Chen, Yu-Ning Wong, Alexander Kutikov, Efrat Dotan, Essel Dulaimi, Reza Mehrazin, Robert G. Uzzo, and Gary R. Hudes, Fox Chase Cancer Center, Temple Health; Jean H. Hoffman-Censits, Edouard J. Trabulsi, Costas D. Lallas, Jianqing Lin, and William Kevin Kelly, Thomas Jefferson University Hospital, Philadelphia, PA; Timothy A. Brennan and Norma Palma, Foundation Medicine, Cambridge, MA; and Stephen A. Boorjian, Mayo Clinic, Rochester, MN.
Reza MehrazinElizabeth R. Plimack, Rosalia Viterbo, Eric A. Ross, Richard E. Greenberg, David Y.T. Chen, Yu-Ning Wong, Alexander Kutikov, Efrat Dotan, Essel Dulaimi, Reza Mehrazin, Robert G. Uzzo, and Gary R. Hudes, Fox Chase Cancer Center, Temple Health; Jean H. Hoffman-Censits, Edouard J. Trabulsi, Costas D. Lallas, Jianqing Lin, and William Kevin Kelly, Thomas Jefferson University Hospital, Philadelphia, PA; Timothy A. Brennan and Norma Palma, Foundation Medicine, Cambridge, MA; and Stephen A. Boorjian, Mayo Clinic, Rochester, MN.
Stephen A BoorjianElizabeth R. Plimack, Rosalia Viterbo, Eric A. Ross, Richard E. Greenberg, David Y.T. Chen, Yu-Ning Wong, Alexander Kutikov, Efrat Dotan, Essel Dulaimi, Reza Mehrazin, Robert G. Uzzo, and Gary R. Hudes, Fox Chase Cancer Center, Temple Health; Jean H. Hoffman-Censits, Edouard J. Trabulsi, Costas D. Lallas, Jianqing Lin, and William Kevin Kelly, Thomas Jefferson University Hospital, Philadelphia, PA; Timothy A. Brennan and Norma Palma, Foundation Medicine, Cambridge, MA; and Stephen A. Boorjian, Mayo Clinic, Rochester, MN.
William Kevin KellyElizabeth R. Plimack, Rosalia Viterbo, Eric A. Ross, Richard E. Greenberg, David Y.T. Chen, Yu-Ning Wong, Alexander Kutikov, Efrat Dotan, Essel Dulaimi, Reza Mehrazin, Robert G. Uzzo, and Gary R. Hudes, Fox Chase Cancer Center, Temple Health; Jean H. Hoffman-Censits, Edouard J. Trabulsi, Costas D. Lallas, Jianqing Lin, and William Kevin Kelly, Thomas Jefferson University Hospital, Philadelphia, PA; Timothy A. Brennan and Norma Palma, Foundation Medicine, Cambridge, MA; and Stephen A. Boorjian, Mayo Clinic, Rochester, MN.
Robert G UzzoElizabeth R. Plimack, Rosalia Viterbo, Eric A. Ross, Richard E. Greenberg, David Y.T. Chen, Yu-Ning Wong, Alexander Kutikov, Efrat Dotan, Essel Dulaimi, Reza Mehrazin, Robert G. Uzzo, and Gary R. Hudes, Fox Chase Cancer Center, Temple Health; Jean H. Hoffman-Censits, Edouard J. Trabulsi, Costas D. Lallas, Jianqing Lin, and William Kevin Kelly, Thomas Jefferson University Hospital, Philadelphia, PA; Timothy A. Brennan and Norma Palma, Foundation Medicine, Cambridge, MA; and Stephen A. Boorjian, Mayo Clinic, Rochester, MN.
Gary R HudesElizabeth R. Plimack, Rosalia Viterbo, Eric A. Ross, Richard E. Greenberg, David Y.T. Chen, Yu-Ning Wong, Alexander Kutikov, Efrat Dotan, Essel Dulaimi, Reza Mehrazin, Robert G. Uzzo, and Gary R. Hudes, Fox Chase Cancer Center, Temple Health; Jean H. Hoffman-Censits, Edouard J. Trabulsi, Costas D. Lallas, Jianqing Lin, and William Kevin Kelly, Thomas Jefferson University Hospital, Philadelphia, PA; Timothy A. Brennan and Norma Palma, Foundation Medicine, Cambridge, MA; and Stephen A. Boorjian, Mayo Clinic, Rochester, MN.
Community Health Center · US

Funding

WORD PROCESSING CENTER--COREP30CA006927 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI Margaret von Mehren · 1985 to 2026
$138.8M
X-Ray Crystallography and Macromolecular CharacterizationP30CA056036 · NCI · THOMAS JEFFERSON UNIVERSITY · PI DANIEL P SILVER · 1995 to 2026
$94.8M
NCI NIH HHS 3 P30 CA-006927-47S4NCI NIH HHS P30CA00692NCI NIH HHS P30 CA006927NCI NIH HHS P30 CA056036
6 · The paper itself

Abstract

purposeNeoadjuvant cisplatin-based chemotherapy is standard of care for muscle-invasive bladder cancer (MIBC); however, it is infrequently adopted in practice because of concerns regarding toxicity and delay to cystectomy. We hypothesized that three cycles of neoadjuvant accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) would be safe, shorten the time to surgery, and yield similar pathologic complete response (pT0) rates compared with historical controls. PATIENTS AND

methodsPatients with cT2-T4a and N0-N1 MIBC were eligible and received three cycles of AMVAC with pegfilgrastim followed by radical cystectomy with lymph node dissection. The primary end point was pT0 rate. Telomere length (TL) and p53 mutation status were correlated with response and toxicity.

resultsForty-four patients were accrued; 60% had stage III to IV disease; median age was 64 years. Forty patients were evaluable for response, with 15 (38%; 95% CI, 23% to 53%) showing pT0 at cystectomy, meeting the primary end point of the study. Another six patients (14%) were downstaged to non-muscle invasive disease. Most (82%) experienced only grade 1 to 2 treatment-related toxicities. There were no grade 3 or 4 renal toxicities and no treatment-related deaths. One patient developed metastases and thus did not undergo cystectomy; all others (n = 43) proceeded to cystectomy within 8 weeks after last chemotherapy administration. Median time from start of chemotherapy to cystectomy was 9.7 weeks. TL and p53 mutation did not predict response or toxicity.

conclusionAMVAC is well tolerated and results in similar pT0 rates with 6 weeks of treatment compared with standard 12-week regimens. Further analysis is ongoing to ascertain whether molecular alterations in tumor samples can predict response to chemotherapy.

Indexed as

AgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBone MarrowCarcinoma, Transitional CellChemotherapy, AdjuvantCisplatinDisease-Free SurvivalDoxorubicinDrug Administration ScheduleFatigueFemaleFilgrastimGene Expression ProfilingGranulocyte Colony-Stimulating FactorBiomarkers, TumorCisplatinDoxorubicinFilgrastimGranulocyte Colony-Stimulating FactorMethotrexatepegfilgrastimPolyethylene GlycolsProtective AgentsRecombinant ProteinsVinblastine

Identifiers

PMID24821881
PMCPMC4050203
OpenAlexW2160107406

What OpenQuestion holds

Textmetadata
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.