Evidence map›Paper›PMID 27793021›Full record

ArticleOncotarget2017

Phase 1 study of sirolimus in combination with oral cyclophosphamide and topotecan in children and young adults with relapsed and refractory solid tumors.

Kieuhoa T Vo, Erin E Karski, Nicole M Nasholm, Shelly Allen, Fabienne Hollinger, W Clay Gustafson, Janel R Long-Boyle, Stephen Shiboski, Katherine K Matthay, Steven G DuBois

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

Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.1field-weighted citation impact, top 20% 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

11 citing papers in PubMed, 19 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

10 authors at 2 institutions in 1 country.

Kieuhoa T VoDepartment of Pediatrics, UCSF Benioff Children's Hospital, University of California, San Francisco School of Medicine, San Francisco, CA, USA.
Erin E KarskiDepartment of Pediatrics, UCSF Benioff Children's Hospital, University of California, San Francisco School of Medicine, San Francisco, CA, USA.
Nicole M NasholmDepartment of Pediatrics, UCSF Benioff Children's Hospital, University of California, San Francisco School of Medicine, San Francisco, CA, USA.
Shelly AllenDepartment of Pediatrics, UCSF Benioff Children's Hospital, University of California, San Francisco School of Medicine, San Francisco, CA, USA.
Fabienne HollingerDepartment of Pediatrics, UCSF Benioff Children's Hospital, University of California, San Francisco School of Medicine, San Francisco, CA, USA.
W Clay GustafsonDepartment of Pediatrics, UCSF Benioff Children's Hospital, University of California, San Francisco School of Medicine, San Francisco, CA, USA.
Janel R Long-BoyleDepartment of Clinical Pharmacy, UCSF Benioff Children's Hospital, University of California, San Francisco School of Medicine, San Francisco, CA, USA.
Stephen ShiboskiDepartment of Epidemiology and Biostatistics, UCSF Benioff Children's Hospital, University of California, San Francisco School of Medicine, San Francisco, CA, USA.
Katherine K MatthayDepartment of Pediatrics, UCSF Benioff Children's Hospital, University of California, San Francisco School of Medicine, San Francisco, CA, USA.
Steven G DuBoisDepartment of Pediatrics, UCSF Benioff Children's Hospital, University of California, San Francisco School of Medicine, San Francisco, CA, USA.
UCSF Benioff Children's Hospital · USUniversity of California, San Francisco · US

Funding

Research Training in Childhood CancerT32CA128583 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Eric Alejandro Sweet-Cordero · 2007 to 2026
$6.0M
NCI NIH HHS T32 CA128583
6 · The paper itself

Abstract

purposeTo determine the maximum tolerated dose (MTD), toxicities, and pharmacodynamics effects of sirolimus combined with oral metronomic topotecan and cyclophosphamide in a pediatric population. MATERIALS AND

methodsPatients who were 1 to 30 years of age with relapsed/refractory solid tumors (including CNS) were eligible. Patients received daily oral sirolimus and cyclophosphamide (25-50 mg/m2/dose) on days 1-21 and oral topotecan (0.8 mg/m2/dose) on days 1-14 in 28-day cycles. Sirolimus steady-state plasma trough concentrations of 3-7.9 ng/mL and 8-12.0 ng/mL were evaluated, with dose escalation based on a 3+3 phase 1 design. Biomarkers of angiogenesis were also evaluated.

resultsTwenty-one patients were treated (median age 18 years; range 9-30). Dose-limiting toxicities included myelosuppression, ALT elevation, stomatitis, and hypertriglyceridemia. The MTD was sirolimus with trough goal of 8-12.0 ng/mL; cyclophosphamide 25 mg/m2/dose; and topotecan 0.8 mg/m2/dose. No objective responses were observed. Four patients had prolonged stable disease > 4 cycles (range 4-12). Correlative biomarker analyses demonstrated reductions in thrombospondin-1 (p=0.043) and soluble vascular endothelial growth factor receptor-2 plasma concentrations at 21 days compared to baseline.

conclusionsThe combination of oral sirolimus, topotecan, and cyclophosphamide was well tolerated and biomarker studies demonstrated modulation of angiogenic pathways with this regimen.

Indexed as

AdolescentAdultAntibiotics, AntineoplasticAntineoplastic Combined Chemotherapy ProtocolsChildCyclophosphamideFemaleHumansMaleNeoplasm Recurrence, LocalNeoplasmsSirolimusTopotecanYoung AdultAntibiotics, AntineoplasticCyclophosphamideSirolimusTopotecancyclophosphamidemTORphase 1sirolimustopotecan

Identifiers

PMID27793021
PMCPMC5410349
OpenAlexW2535297451

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.