Evidence map›Paper›PMID 26916138›Full record

ArticleCancer2016

Beyond the dose-limiting toxicity period: Dermatologic adverse events of patients on phase 1 trials of the Cancer Therapeutics Evaluation Program.

Alexander Drilon, Anne A Eaton, Katja Schindler, Mrinal M Gounder, David R Spriggs, Pamela Harris, S Percy Ivy, Alexia Iasonos, Mario E Lacouture, David M Hyman

Abstract readEvaluation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–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

6 citing papers in PubMed.

  1. Benralizumab for Eosinophil-Related Cutaneous Adverse Events of Anticancer Therapy: A Phase II Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Trial
  2. Article
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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.

Alexander DrilonDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Anne A EatonDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Katja SchindlerDermatology Department, Medical University of Vienna, Vienna, Austria.
Mrinal M GounderDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
David R SpriggsDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Pamela HarrisCancer Therapeutics and Evaluation Program, National Cancer Institute, Bethesda, Maryland.
S Percy IvyCancer Therapeutics and Evaluation Program, National Cancer Institute, Bethesda, Maryland.
Alexia IasonosDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Mario E LacoutureDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
David M HymanDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

backgroundDermatologic adverse events (AEs) can be key determinants of overall drug tolerability and of the maximum tolerated and recommended phase 2 doses in phase 1 trials. The authors present the largest dedicated analysis of dermatologic AEs on phase 1 trials to date.

methodsData from a prospectively maintained database of patients with solid tumors who were enrolled onto Cancer Therapeutics Evaluation Program (CTEP)-sponsored phase 1 trials of cytotoxic or molecularly targeted agents (MTAs) from 2000 to 2010 were analyzed. Cumulative incidence, site, and type of drug-related dermatologic AEs were described and compared. The timing of worst drug-related dermatologic AEs was summarized.

resultsIn total, 3517 patients with solid tumors and 6165 unique, drug-related dermatologic AEs were analyzed, including 1545 patients on MTA-only trials, 671 on cytotoxic-only trials, and 1392 on combination MTA and cytotoxic trials. Of 1270 patients who had drug-related dermatologic events, the timing of the worst AE was as follows: 743 (cycle 1), 303 (cycle 2), and 224 (cycle 3 or later). Although the cumulative incidence of grade ≥3 drug-related AEs increased to 2.4% by cycle 6, it was only 1.6% at the end of cycle 1. The cumulative incidence of drug-related AEs was highest in patients who received MTA-only therapy (P < .001) and differed by dose level (P < .001). In patients who received MTA-only therapy, drug-related AEs were most common for combination kinase inhibitor-containing therapy (P < .001).

conclusionsA substantial proportion of drug-related dermatologic AEs occur after the traditional dose-limiting toxicity monitoring period of phase 1 clinical trials. Future designs should account for late toxicities.

Indexed as

Antineoplastic AgentsClinical Trials, Phase I as TopicDatabases, FactualDose-Response Relationship, DrugDrug EruptionsFemaleFollow-Up StudiesHumansIncidenceMaleMaximum Tolerated DoseMolecular Targeted TherapyNeoplasmsRetrospective StudiesRisk AssessmentSeverity of Illness IndexAntineoplastic AgentsCancer Therapeutics Evaluation Program (CTEP)dermatologic toxicitydose-limiting toxicity (DLT) periodmolecularly targeted agentsphase 1 trial

Identifiers

PMID26916138
PMCPMC5479632

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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.