Investigational New Drugs

, Volume 37, Issue 1, pp 166–174 | Cite as

Global trends in the distribution of cancer types among patients in oncology phase I trials, 1991–2015

  • Kota Itahashi
  • Toshio Shimizu
  • Takafumi Koyama
  • Shunsuke Kondo
  • Yutaka Fujiwara
  • Noboru YamamotoEmail author


Background Systematic analyses regarding cancer types of patients enrolled in oncology phase I trials are scarce. The global distribution, time-dependent change, and regional differences were evaluated. Methods A systematic search of the PubMed database, in which all single-agent phase I trials permitting the enrollment of all-comer patients with any type of solid tumor published between January 1991 and December 2015 were specified, was performed. Trials expected to enroll specific patient populations were excluded according to predefined criteria. Results Eight hundred and sixty-six eligible trials, which had enrolled 29,112 advanced solid tumor patients, were identified. Colorectal (n = 7510; 25.8%) and lung cancer (n = 3212; 11.0%) were the most prevalent solid tumors, followed by sarcoma (n = 1756; 6.0%), breast cancer (n = 1623; 5.6%), and renal cancer (n = 1589; 5.5%). The proportion of patients with either colorectal or lung cancer tended to decrease over time. The proportion of trials, in which patients with either of these two cancers accounted for ≥50.0% of the total number of patients in each trial, also decreased: 33 of 67 trials (31/67) (46.3%) in 1991–1995, 58/142 (40.8%) in 1996–2000, 59/223 (26.5%) in 2001–2005, 38/189 (20.1%) in 2006–2010, and 41/245 (16.7%) in 2011–2015. Instead, the proportion of patients with various types of cancer increased, leading to diversification of enrolled patients. Conclusions The distribution of cancer types among patients in phase I trials has changed. The comprehensive review of the distribution of solid tumor types could contribute to flexible trial designs and optimal patient recruitment.


Phase I trial Cancer Cancer type Global trend 


Author contributions

Itahashi and Yamamoto had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Itahashi, Yamamoto.

Acquisition, analysis, or interpretation of data: all authors.

Drafting of the manuscript: Itahashi, Shimizu, Yamamoto.

Critical revision of the manuscript for important intellectual content: all authors.

Statistical analysis: Itahashi.

Administrative, technical, or material support: Koyama, Yamamoto.

Study Supervision: Yamamoto.

Compliance with ethical standards

Conflict of interest disclosures

Kota Itahashi has no conflicts of interest.

Toshio Shimizu has provided consulting for Takeda Oncology; received honoraria from Ono Pharmaceutical, ONO Pharma Taiwan CO., LTD., Boehringer Ingelheim, Taiho Pharmaceutical and Chugai Pharmaceutical; and received research funding from Takeda Oncology, PharmaMar, Bristol-Myers Squibb Japan, Daiichi Sankyo, SymBio Pharmaceuticals, Five Prime Therapeutics, and 3D Medicine.

Takafumi Koyama has no conflicts of interest.

Shunsuke Kondo has received research funding from Astrazeneca, Eli Lilly, and Pfizer.

Yutaka Fujiwara has provided consulting for Ono Pharmaceutical and Bristol-Myers Squibb Japan; participated in speakers’ bureau for Ono Pharmaceutical, Bristol-Myers Squibb Japan, MSD, and Taiho Pharmaceutical; and received research funding from AstraZeneca, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Lilly Japan, Novartis, Bristol-Myers Squibb Japan, MSD, Merck Serono, Abbvie, and Incyte.

Noboru Yamamoto has provided consulting for Eisai, Takeda, Otsuka Pharmaceutical, and OncoTherapy Science; participated in speakers’ bureau for Bristol-Myers Squibb Japan, Pfizer, AstraZeneca, Lilly Japan, Ono Pharmaceutical, and Chugai Pharmaceutical; and received research funding from Chugai Pharmaceutical, Taiho Pharmaceutical, Eisai, Quintiles, Astellas Pharma, Novartis, Daiichi Sankyo, Boehringer Ingelheim, Takeda, Kyowa Hakko Kirin, Bayer, Pfizer, Bristol-Myers Squibb Japan, Ono Pharmaceutical, and Bayer.

Research involving human participants and/or animals

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

For this type of study formal consent is not required.

Meeting presentation

We presented this work at the Annual Meeting of the American Society of Clinical Oncology; June 2–6, 2017; Chicago, Illinois.


All opinions expressed by the authors in this paper are solely the author’s opinions and do not reflect the opinions of the journal.

Supplementary material

10637_2018_654_MOESM1_ESM.pdf (90 kb)
Supplementary Fig. S1 (PDF 89 kb)
10637_2018_654_MOESM2_ESM.pdf (159 kb)
Supplementary Table S1 (PDF 159 kb)
10637_2018_654_MOESM3_ESM.pdf (97 kb)
Supplementary Table S2 (PDF 97 kb)
10637_2018_654_MOESM4_ESM.pdf (196 kb)
Supplementary Table S3 (PDF 195 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Kota Itahashi
    • 1
  • Toshio Shimizu
    • 1
  • Takafumi Koyama
    • 1
  • Shunsuke Kondo
    • 1
  • Yutaka Fujiwara
    • 1
  • Noboru Yamamoto
    • 1
    Email author
  1. 1.Department of Experimental TherapeuticsNational Cancer Center HospitalTokyoJapan

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