Evidence map›Paper›PMID 33507338›Full record

ArticleCancer chemotherapy and pharmacology2021

Extrapolation of pharmacokinetics and pharmacodynamics of sunitinib in children with gastrointestinal stromal tumors.

Reza Khosravan, Steven G DuBois, Katherine Janeway, Erjian Wang

Open access · hybridAbstract read
In one paragraph

Article in Cancer chemotherapy and pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
1.0field-weighted citation impact, top 26% 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, 1 synthesis or guideline pooled it, 8 citations in OpenAlex.

  1. Pooled it
  2. Review
  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

4 authors at 2 institutions in 1 country.

Reza KhosravanPfizer Inc, Oncology Clinical Pharmacology, 10646 Science Center Drive, CB10, Pfizer Oncology, La Jolla, CA, 92121, USA. Reza.Khosravan@pfizer.com.ORCID http://orcid.org/0000-0002-4181-8728
Steven G DuBoisPediatric Hematology/Oncology, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA, USA.
Katherine JanewayPediatric Hematology/Oncology, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA, USA.
Erjian WangPfizer Inc, Oncology Clinical Pharmacology, 10646 Science Center Drive, CB10, Pfizer Oncology, La Jolla, CA, 92121, USA.
Harvard University · USPfizer (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeThe starting dose of sunitinib in children with gastrointestinal stromal tumors (GIST) was extrapolated based on data in adults with GIST or solid tumors and children with solid tumors.

methodsIntegrated population pharmacokinetics (PK), PK/pharmacodynamics (PD), and exposure-response analyses using nonlinear mixed-effects modeling approaches were performed to extrapolate PK and PD of sunitinib in children with GIST at projected dose(s) with plasma drug exposures comparable to 50-mg/day in adults with GIST. The analysis datasets included PK/PD data in adults with GIST and adults and children with solid tumors. The effect of covariates on PK and safety/efficacy endpoints were explored.

resultsTwo-compartment models with lag time were successfully used to describe the PK of sunitinib and its active metabolite SU012662. PK/PD models were successfully built to describe key continuous safety and efficacy endpoints. The effect of age on sunitinib apparent clearance (CL/F) and body surface area on SU012662 CL/F was statistically significant (P ≤ 0.001): children who were younger or of smaller body size had lower CL/F; however, age and body size did not appear to negatively affect safety or efficacy response to plasma drug exposure.

conclusionBased on PK, safety, and efficacy trial simulations, a sunitinib starting dose of ~ 25 mg/m

Indexed as

AdolescentAdultAgedAged, 80 and overChildChild, PreschoolGastrointestinal NeoplasmsGastrointestinal Stromal TumorsHumansMiddle AgedModels, BiologicalSunitinibYoung AdultSunitinibDose extrapolationGastrointestinal stromal tumorPediatric cancerSunitinib

Identifiers

PMID33507338
PMCPMC8026416
OpenAlexW3121669850

What OpenQuestion holds

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LicenceCC BY
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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.