Evidence map›Paper›PMID 26632033›Full record

ArticleJournal of clinical pharmacology2016

Phase 1 Study of ABT-751 in Combination With CAPIRI (Capecitabine and Irinotecan) and Bevacizumab in Patients With Advanced Colorectal Cancer.

Michelle A Rudek, Arvind Dasari, Daniel Laheru, Ping He, Runyan Jin, Rosalind Walker, Gretchen E Taylor, Antonio Jimeno, Ross C Donehower, Manuel Hidalgo and 2 more

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

Article in Journal of clinical pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 37% 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

3 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Article
  3. 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

12 authors at 4 institutions in 2 countries.

Michelle A RudekSidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
Arvind DasariUniversity of Colorado Cancer Center, Denver, CO, USA.
Daniel LaheruSidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
Ping HeSidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
Runyan JinSidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
Rosalind WalkerSidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
Gretchen E TaylorSidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
Antonio JimenoSidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
Ross C DonehowerSidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
Manuel HidalgoSidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
Wells A MessersmithSidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
W Thomas PurcellSidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
Johns Hopkins University · USSidney Kimmel Comprehensive Cancer Center · USUniversity of Colorado Cancer Center · USCentro Oncológico de Galicia · ES

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

ABT-751 is an orally bioavailable sulfonamide with antimitotic properties. A nonrandomized phase 1 dose-escalation study of ABT-751 in combination with CAPIRI (capecitabine and irinotecan) and bevacizumab was conducted to define the maximum tolerated dose, dose-limiting toxicity (DLT), and pharmacokinetics in patients with advanced colorectal cancer. Patients were treated with ABT-751 daily for 7 days (alone) and then began 21-day cycles of treatment with ABT-751 daily and capecitabine twice daily for 14 days plus irinotecan on day 1 intravenously. Bevacizumab was added as standard of care at 7.5 mg/kg on day 1 after the first 2 dose levels. Because of intolerance to the regimen, a reduced dose of ABT-751 was also explored with reduced-dose and full-dose CAPIRI with bevacizumab. ABT-751 and irinotecan pharmacokinetics, ABT-751 glucuronidation, and protein binding were explored. Twenty-four patients were treated over 5 dose levels. The maximum tolerated dose was ABT-751 125 mg combined with full-dose CAPIRI and bevacizumab 7.5 mg/kg on day 1. DLTs were hypokalemia, elevated liver tests, and febrile neutropenia. ABT-751 is metabolized by UGT1A8 and to a lesser extent UGT1A4 and UGT1A1. Irinotecan and APC exposure were increased, SN-38 exposure was similar, and SN-38 glucuronide exposure was decreased. Clinically relevant alterations in ABT-751 and irinotecan pharmacokinetics were not observed. Despite modest efficacy, the combination of ABT-751, CAPIRI, and bevacizumab will not be studied further in colorectal cancer.

Indexed as

AdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBevacizumabCamptothecinColorectal NeoplasmsDeoxycytidineDrug Therapy, CombinationFemaleFluorouracilFollow-Up StudiesHumansMaleMiddle AgedSulfonamidesABT751BevacizumabCamptothecinDeoxycytidineFluorouracilSulfonamidescolorectal cancerpharmacokineticstoxicitytubulin inhibitor

Identifiers

PMID26632033
PMCPMC4892995
OpenAlexW2192585329

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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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.