Evidence map›Paper›PMID 26848151›Full record

ArticleJournal of the National Cancer Institute2016

Veliparib Alone or in Combination with Mitomycin C in Patients with Solid Tumors With Functional Deficiency in Homologous Recombination Repair.

Miguel A Villalona-Calero, Wenrui Duan, Weiqiang Zhao, Konstantin Shilo, Larry J Schaaf, Jennifer Thurmond, Judith A Westman, John Marshall, Li Xiaobai, Jiuping Ji and 5 more

Open access · bronzeAbstract readControlled Clinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of the National Cancer Institute, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 18% 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

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.

  1. Pooled it
  2. Hypoxia alters the response of ovarian cancer cells to the mitomycin C drug.Frontiers in cell and developmental biology · 2025
    Article
  3. Article
  4. Review
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  7. Review
  8. Towards Personalized Management of Ovarian Cancer.Cancer management and research · 2022
    Review
  9. Article
  10. Review
  11. Review
  12. Review
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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 4 institutions in 1 country.

Miguel A Villalona-CaleroDivisions of Medical Oncology (MAVC, WD, JR, ML, TBS) and Clinical Cancer Genetics (JAW), Department of Pathology (WZ, KS), Comprehensive Cancer Center (MAVC, WD, LJS, JT, TBS, CT), and Center for Biostatistics (LX), The Ohio State University , Columbus, OH ; Lombardi Cancer Center, Georgetown University , Washington, DC (JM); National Cancer Institute , Bethesda, MD (JJ, AC).
Wenrui DuanDivisions of Medical Oncology (MAVC, WD, JR, ML, TBS) and Clinical Cancer Genetics (JAW), Department of Pathology (WZ, KS), Comprehensive Cancer Center (MAVC, WD, LJS, JT, TBS, CT), and Center for Biostatistics (LX), The Ohio State University , Columbus, OH ; Lombardi Cancer Center, Georgetown University , Washington, DC (JM); National Cancer Institute , Bethesda, MD (JJ, AC).
Weiqiang ZhaoDivisions of Medical Oncology (MAVC, WD, JR, ML, TBS) and Clinical Cancer Genetics (JAW), Department of Pathology (WZ, KS), Comprehensive Cancer Center (MAVC, WD, LJS, JT, TBS, CT), and Center for Biostatistics (LX), The Ohio State University , Columbus, OH ; Lombardi Cancer Center, Georgetown University , Washington, DC (JM); National Cancer Institute , Bethesda, MD (JJ, AC).
Konstantin ShiloDivisions of Medical Oncology (MAVC, WD, JR, ML, TBS) and Clinical Cancer Genetics (JAW), Department of Pathology (WZ, KS), Comprehensive Cancer Center (MAVC, WD, LJS, JT, TBS, CT), and Center for Biostatistics (LX), The Ohio State University , Columbus, OH ; Lombardi Cancer Center, Georgetown University , Washington, DC (JM); National Cancer Institute , Bethesda, MD (JJ, AC).
Larry J SchaafDivisions of Medical Oncology (MAVC, WD, JR, ML, TBS) and Clinical Cancer Genetics (JAW), Department of Pathology (WZ, KS), Comprehensive Cancer Center (MAVC, WD, LJS, JT, TBS, CT), and Center for Biostatistics (LX), The Ohio State University , Columbus, OH ; Lombardi Cancer Center, Georgetown University , Washington, DC (JM); National Cancer Institute , Bethesda, MD (JJ, AC).
Jennifer ThurmondDivisions of Medical Oncology (MAVC, WD, JR, ML, TBS) and Clinical Cancer Genetics (JAW), Department of Pathology (WZ, KS), Comprehensive Cancer Center (MAVC, WD, LJS, JT, TBS, CT), and Center for Biostatistics (LX), The Ohio State University , Columbus, OH ; Lombardi Cancer Center, Georgetown University , Washington, DC (JM); National Cancer Institute , Bethesda, MD (JJ, AC).
Judith A WestmanDivisions of Medical Oncology (MAVC, WD, JR, ML, TBS) and Clinical Cancer Genetics (JAW), Department of Pathology (WZ, KS), Comprehensive Cancer Center (MAVC, WD, LJS, JT, TBS, CT), and Center for Biostatistics (LX), The Ohio State University , Columbus, OH ; Lombardi Cancer Center, Georgetown University , Washington, DC (JM); National Cancer Institute , Bethesda, MD (JJ, AC).
John MarshallDivisions of Medical Oncology (MAVC, WD, JR, ML, TBS) and Clinical Cancer Genetics (JAW), Department of Pathology (WZ, KS), Comprehensive Cancer Center (MAVC, WD, LJS, JT, TBS, CT), and Center for Biostatistics (LX), The Ohio State University , Columbus, OH ; Lombardi Cancer Center, Georgetown University , Washington, DC (JM); National Cancer Institute , Bethesda, MD (JJ, AC).
Li XiaobaiDivisions of Medical Oncology (MAVC, WD, JR, ML, TBS) and Clinical Cancer Genetics (JAW), Department of Pathology (WZ, KS), Comprehensive Cancer Center (MAVC, WD, LJS, JT, TBS, CT), and Center for Biostatistics (LX), The Ohio State University , Columbus, OH ; Lombardi Cancer Center, Georgetown University , Washington, DC (JM); National Cancer Institute , Bethesda, MD (JJ, AC).
Jiuping JiDivisions of Medical Oncology (MAVC, WD, JR, ML, TBS) and Clinical Cancer Genetics (JAW), Department of Pathology (WZ, KS), Comprehensive Cancer Center (MAVC, WD, LJS, JT, TBS, CT), and Center for Biostatistics (LX), The Ohio State University , Columbus, OH ; Lombardi Cancer Center, Georgetown University , Washington, DC (JM); National Cancer Institute , Bethesda, MD (JJ, AC).
Jeffrey RoseDivisions of Medical Oncology (MAVC, WD, JR, ML, TBS) and Clinical Cancer Genetics (JAW), Department of Pathology (WZ, KS), Comprehensive Cancer Center (MAVC, WD, LJS, JT, TBS, CT), and Center for Biostatistics (LX), The Ohio State University , Columbus, OH ; Lombardi Cancer Center, Georgetown University , Washington, DC (JM); National Cancer Institute , Bethesda, MD (JJ, AC).
Maryam LustbergDivisions of Medical Oncology (MAVC, WD, JR, ML, TBS) and Clinical Cancer Genetics (JAW), Department of Pathology (WZ, KS), Comprehensive Cancer Center (MAVC, WD, LJS, JT, TBS, CT), and Center for Biostatistics (LX), The Ohio State University , Columbus, OH ; Lombardi Cancer Center, Georgetown University , Washington, DC (JM); National Cancer Institute , Bethesda, MD (JJ, AC).
Tanios Bekaii-SaabDivisions of Medical Oncology (MAVC, WD, JR, ML, TBS) and Clinical Cancer Genetics (JAW), Department of Pathology (WZ, KS), Comprehensive Cancer Center (MAVC, WD, LJS, JT, TBS, CT), and Center for Biostatistics (LX), The Ohio State University , Columbus, OH ; Lombardi Cancer Center, Georgetown University , Washington, DC (JM); National Cancer Institute , Bethesda, MD (JJ, AC).
Alice ChenDivisions of Medical Oncology (MAVC, WD, JR, ML, TBS) and Clinical Cancer Genetics (JAW), Department of Pathology (WZ, KS), Comprehensive Cancer Center (MAVC, WD, LJS, JT, TBS, CT), and Center for Biostatistics (LX), The Ohio State University , Columbus, OH ; Lombardi Cancer Center, Georgetown University , Washington, DC (JM); National Cancer Institute , Bethesda, MD (JJ, AC).
Cynthia TimmersDivisions of Medical Oncology (MAVC, WD, JR, ML, TBS) and Clinical Cancer Genetics (JAW), Department of Pathology (WZ, KS), Comprehensive Cancer Center (MAVC, WD, LJS, JT, TBS, CT), and Center for Biostatistics (LX), The Ohio State University , Columbus, OH ; Lombardi Cancer Center, Georgetown University , Washington, DC (JM); National Cancer Institute , Bethesda, MD (JJ, AC).
Georgetown University Medical Center · USThe Ohio State University · USCancer Genetics (United States) · USGeorgetown University · US

Funding

Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Tasleem J Padamsee · 1985 to 2026
$132.3M
Therapuetic Immune Targeting of EphA2 Expressed by Melanoma & Its Tumor-AssociateP50CA121973 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KIRKWOOD, JOHN MUNN · 2008 to 2018
$22.9M
UM1 Supplement for Early Therapeutic Trials with Phase 2 IntentUM1CA186712 · NCI · OHIO STATE UNIVERSITY · PI SUSANNE M ARNOLD, WILLIAM E. CARSON · 2014 to 2026
$19.3M
Targeting Somatic Homologous Recombination in Solid TumorsR01CA152101 · NCI · OHIO STATE UNIVERSITY · PI VILLALONA, MIGUEL A · 2010 to 2014
$2.3M
Discovery of Homologous Recombination DNA Repair Deficiency in Lung TumorR21CA181291 · NCI · OHIO STATE UNIVERSITY · PI DUAN, WENRUI · 2014 to 2015
$368k
NCI NIH HHS N01-CM-2011-00070NCI NIH HHS P30 CA016058NCI NIH HHS P30 CA016058-38NCI NIH HHS P50CA121973NCI NIH HHS R01 CA152101NCI NIH HHS R21 CA181291NCI NIH HHS UM1 CA186712
6 · The paper itself

Abstract

backgroundBRCA germline mutations are being targeted for development of PARP inhibitors. BRCA genes collaborate with several others in the Fanconi Anemia (FA) pathway. We screened cancer patients' tumors for FA functional defects then aimed to establish the safety/feasibility of administering PARP inhibitors as monotherapy and combined with a DNA-breaking agent.

methodsPatients underwent FA functional screening for the presence (or lack) of tumor FancD2 nuclear foci formation on their archival tumor material, utilizing a newly developed method (Fanconi Anemia triple-stain immunofluorescence [FATSI]), performed in a Clinical Laboratory Improvement Amendments-certified laboratory. FATSI-negative patients were selected for enrollment in a two-arm dose escalation trial of veliparib, or veliparib/mitomycin-C (MMC).

resultsOne hundred eighty-five of 643 (28.7%) screened patients were FATSI-negative. Sixty-one received veliparib or veliparib/MMC through 14 dose levels. Moderate/severe toxicities included fatigue (DLT at veliparib 400mg BID), diarrhea, and thrombocytopenia. Recommended doses are 300mg BID veliparib and veliparib 200mg BID for 21 days following 10mg/m(2) MMC every 28 days. Six antitumor responses occurred, five in the combination arm (3 breast, 1 ovarian, 1 endometrial [uterine], and 1 non-small cell lung cancer). Two patients have received 36 and 60 cycles to date. BRCA germline analysis among 51 patients revealed five deleterious mutations while a targeted FA sequencing gene panel showed missense/nonsense mutations in 29 of 49 FATSI-negative tumor specimens.

conclusionsFATSI screening showed that a substantial number of patients' tumors have FA functional deficiency, which led to germline alterations in several patients' tumors. Veliparib alone or with MMC was safely administered to these patients and produced clinical benefit in some. However, a better understanding of resistance mechanisms in this setting is needed.

Indexed as

Recombinational DNA RepairAdultAgedAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBenzimidazolesDiarrheaDrug Administration ScheduleFanconi AnemiaFatigueFeasibility StudiesFemaleGenes, BRCA1Genes, BRCA2Germ-Line MutationHumansAntineoplastic AgentsBenzimidazolesMitomycinPoly(ADP-ribose) Polymerase Inhibitorsveliparib

Identifiers

PMID26848151
PMCPMC4948564
OpenAlexW2314899769

What OpenQuestion holds

Textmetadata
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.