Evidence map›Paper›PMID 28424323›Full record

SynthesisThe oncologist2017

Dosing Three-Drug Combinations That Include Targeted Anti-Cancer Agents: Analysis of 37,763 Patients.

Mina Nikanjam, Sariah Liu, Jincheng Yang, Razelle Kurzrock

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in The oncologist, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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

32 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
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  3. Trial
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  5. Observational
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  11. Cancer: slaying the nine-headed Hydra.Annals of oncology : official journal of the European Society for Medical Oncology · 2023
    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

4 authors.

Mina NikanjamDivision of Hematology-Oncology, University of California Los Angeles, Los Angeles, California, USA mnikanjam@mednet.ucla.edu.
Sariah LiuDepartment of Hematology-Oncology, Kaiser Permanente San Diego Medical Center, San Diego, California, USA.
Jincheng YangSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, California, USA.
Razelle KurzrockCenter for Personalized Cancer Therapy and Division of Hematology and Oncology, UC San Diego Moores Cancer Center, San Diego, California, USA.

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
Training for Academic HematologyT32HL066992 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHUTE, JOHN P, TIMMERMAN, JOHN M · 2002 to 2017
$3.6M
NCI NIH HHS P30 CA016672NHLBI NIH HHS T32 HL066992
6 · The paper itself

Abstract

backgroundCombining targeted and cytotoxic agents has the potential to improve efficacy and attenuate resistance for metastatic cancer. Information regarding safe starting doses for clinical trials of novel three-drug combinations is lacking. MATERIALS AND

methodsPublished phase I-III adult oncology clinical trials of three-drug combinations involving a targeted agent were identified by PubMed search (January 1, 2010 to December 31, 2013). A dose percentage was calculated to compare the dose used in combination to the single agent recommended dose: (U.S. Food and Drug Administration-approved/recommended phase II dose/maximum tolerated dose). The additive dose percentage was the sum of the dose percentages for each drug in the combination.

resultsA total of 37,763 subjects and 243 drug combinations were included. Only 28% of studies could give each of the three agents at 100%. For combinations involving two targeted agents and a cytotoxic agent, the lowest starting additive dose percentage was 133%, which increased to 250% if two antibodies were included. For combinations of one targeted agent and two cytotoxic agents, the lowest additive safe dose percentage was 137%. When both cytotoxic agents were held at 100%, as occurred in 56% of studies (which generally used cytotoxic doublets with known combination safety dosing), the lowest safe dose percentage was 225% (providing that a histone deacetylase inhibitor was not the targeted agent).

conclusionThese findings serve as a safe starting point for dosing novel three-drug combinations involving a targeted agent in clinical trials and practice.

Indexed as

Antineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsClinical Trials as TopicDose-Response Relationship, DrugHistone Deacetylase InhibitorsHumansNeoplasmsAntineoplastic AgentsHistone Deacetylase InhibitorsCytotoxic chemotherapyMaximum tolerated dosePrecision medicineRecommended phase II doseTargeted therapy

Identifiers

PMID28424323
PMCPMC5423521

What OpenQuestion holds

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Registered trials

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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.