Evidence map›Paper›PMID 24764124›Full record

Trial reportInvestigational new drugs2014

Targeting DNA repair with combination veliparib (ABT-888) and temozolomide in patients with metastatic castration-resistant prostate cancer.

Maha Hussain, Michael A Carducci, Susan Slovin, Jeremy Cetnar, Jiang Qian, Evelyn M McKeegan, Marion Refici-Buhr, Brenda Chyla, Stacie P Shepherd, Vincent L Giranda and 1 more

Registry-linked trialAbstract readClinical TrialMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Investigational new drugs, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01085422 (A Pilot Study Combining ABT-888, an Oral PARP Inhibitor, With Temozolomide in Patients With Metastatic Castration Resistant Prostate Cancer Who Have Failed Up to Two Non-hormonal Systemic Therapies), which is not on this map. Cited by 57 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 3 pooled it
3.9field-weighted citation impact, top 5% 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.

NCT01085422 phase1completednot on this map

A Pilot Study Combining ABT-888, an Oral PARP Inhibitor, With Temozolomide in Patients With Metastatic Castration Resistant Prostate Cancer Who Have Failed Up to Two Non-hormonal Systemic Therapies

TypeinterventionalSponsorAbbVie (prior sponsor, Abbott)Ran2010 to 2011Enrolled35ConditionsProstate CancerArmsABT-888, temozolomide
3 · Its place in the literature

Who cites it

57 citing papers in PubMed, 3 syntheses or guidelines pooled it, 95 citations in OpenAlex.

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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

11 authors at 7 institutions in 1 country.

Maha HussainComprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA, mahahuss@med.umich.edu.
Michael A Carducci
Susan Slovin
Jeremy Cetnar
Jiang Qian
Evelyn M McKeegan
Marion Refici-Buhr
Brenda Chyla
Stacie P Shepherd
Vincent L Giranda
Joshi J Alumkal
AbbVie (Japan)AbbVie (United States) · USMemorial Sloan Kettering Cancer Center · USOregon Health & Science University · USSidney Kimmel Comprehensive Cancer Center · USUniversity of Michigan–Ann Arbor · USUniversity of Wisconsin Carbone Cancer Center · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
NCI NIH HHS P30 CA006973
6 · The paper itself

Abstract

Androgen receptor-mediated transcription is directly coupled with the induction of DNA damage, and castration-resistant tumor cells exhibit increased activity of poly (ADP-ribose) polymerase (PARP)-1, a DNA repair enzyme. This study assessed the efficacy and safety of low dose oral PARP inhibitor veliparib (ABT-888) and temozolomide (TMZ) in docetaxel-pretreated patients with metastatic castration-resistant prostate cancer (mCRPC) in a single-arm, open-label, pilot study. Patients with mCRPC progressing on at least one docetaxel-based therapy and prostate specific antigen (PSA) ≥ 2 ng/mL were treated with veliparib 40 mg twice daily on days 1-7 and TMZ once daily (150 mg/m(2)/day cycle 1; if well tolerated then 200 mg/m(2)/day cycle 2 onwards) on days 1-5 q28 days. Patients received 2 (median) treatment cycles (range, 1-9). The primary endpoint was confirmed PSA response rate (decline ≥ 30 %). Twenty-six eligible patients were enrolled, 25 evaluable for PSA response. Median baseline PSA was 170 ng/mL. Two patients had a confirmed PSA response (8.0 %; 95 % CI: 1.0-26.0), 13 stable PSA, and 10 PSA progression. The median progression-free survival was 9 weeks (95 % CI: 7.9-17) and median overall survival 39.6 weeks (95 % CI: 26.6-not estimable). The most frequent treatment-emergent adverse events (AEs) were thrombocytopenia (77 %), anemia (69 %), fatigue (50 %), neutropenia (42 %), nausea (38 %), and constipation (23 %). Grade 3/4 AEs occurring in > 10 % of patients were thrombocytopenia (23 %) and anemia (15 %). Veliparib and TMZ combination was well tolerated but with modest activity. Biomarker analysis supported the proof of concept that this combination has some antitumor activity in mCRPC.

Indexed as

AgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBenzimidazolesDacarbazineDNA RepairHumansKallikreinsMaleMiddle AgedPilot ProjectsPoly(ADP-ribose) Polymerase InhibitorsProstate-Specific AntigenProstatic Neoplasms, Castration-ResistantTemozolomideTreatment OutcomeBenzimidazolesDacarbazineKallikreinsKLK3 protein, humanPoly(ADP-ribose) Polymerase InhibitorsProstate-Specific AntigenTemozolomideveliparib

Identifiers

PMID24764124
PMCPMC4659356
OpenAlexW2037352738

What OpenQuestion holds

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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.