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Characterization and outcomes of patients enrolled to multiple phase I cancer trials

  • Nathan Kuehne
  • Lina Chen
  • Kate McDonald
  • Lisa Wang
  • Anna Spreafico
  • Aaron Hansen
  • Albiruni Ryan Abdul Razak
  • Philippe Lucien Bedard
  • Lillian L. Siu
  • Daniel ShepshelovichEmail author
Short Communication
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Abstract

Purpose

Some patients who participate in early phase cancer trials enroll to more than one trial. Whether these patients have different characteristics or outcomes than patients who enroll to a single phase I trial is unknown.

Methods

The study included all patients who participated in the solid tumor drug development program of the Princess Margaret Cancer Centre, a specialized academic cancer center, from July 2014 to January 2017. Patients sequentially enrolled to multiple phase I trials were compared to those enrolled in a single trial according to demographics, clinical characteristics, reported toxicities and prognosis.

Results

The study cohort included 328 patients, including 61 (19%) enrolled to multiple phase I trials and 267 (81%) enrolled to a single phase I trial. Demographics, comorbidities, performance status, cancer site and time between initial diagnosis and initial enrollment to the phase I program were comparable between both groups. Patients enrolled to multiple phase I trials received more previous non-trial treatment lines (median 3 versus 2, p < 0.001) and had a higher average response rate on phase I trials (18% versus 10%, p = 0.03). Toxicity data, including number of any adverse events (AEs), grade 3/4 AEs, serious AEs and dose-limiting toxicities were comparable between both groups. Time to disease progression and time to last documented follow-up were also comparable between both groups.

Conclusions

Patients enrolled to multiple phase I trials and those enrolled to a single trial had similar toxicity and prognostic profiles. These patients do not introduce bias into early-phase cancer trials results.

Keywords

Cancer Phase I Multiple Toxicity Prognosis 

Notes

Compliance with ethical standards

Conflict of interest

All authors declare no COI potentially influencing the research reported in this manuscript. Daniel Shepshelovich takes full responsibility for the presented data and analyses.

References

  1. 1.
    Le Tourneau C, Lee JJ, Siu LL (2009) Dose escalation methods in phase I cancer clinical trials. J Natl Cancer Inst 101(10):708–720CrossRefGoogle Scholar
  2. 2.
    NCI Dictionary of Cancer Terms. https://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=44170. Accessed 7 Nov 2019
  3. 3.
    Wong HH, Barton C, Acton G, McLeod R, Halford S (2016) Trends in the characteristics, dose-limiting toxicities and efficacy of phase I oncology trials: the Cancer Research UK experience. Eur J Cancer 66:9–16CrossRefGoogle Scholar
  4. 4.
    Rogatko A, Babb JS, Wang H, Slifker MJ, Hudes GR (2004) Patient characteristics compete with dose as predictors of acute treatment toxicity in early phase clinical trials. Clin Cancer Res 10(14):4645–4651CrossRefGoogle Scholar
  5. 5.
    Quan H, Li B, Couris CM, Fushimi K, Graham P, Hider P, Januel JM, Sundararajan V (2011) Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. Am J Epidemiol 173(6):676–682.  https://doi.org/10.1093/aje/kwq433Epub 2011 Feb 17 CrossRefPubMedGoogle Scholar
  6. 6.
    Eisenhauera EA, Therasseb P, Bogaertsc J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45(2):228–247CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Nathan Kuehne
    • 1
  • Lina Chen
    • 1
  • Kate McDonald
    • 1
  • Lisa Wang
    • 1
  • Anna Spreafico
    • 1
    • 2
  • Aaron Hansen
    • 1
    • 2
  • Albiruni Ryan Abdul Razak
    • 1
    • 2
  • Philippe Lucien Bedard
    • 1
    • 2
  • Lillian L. Siu
    • 1
    • 2
  • Daniel Shepshelovich
    • 1
    • 2
    • 3
    • 4
    Email author
  1. 1.Division of Medical Oncology and Hematology, University Health NetworkPrincess Margaret Cancer CentreTorontoCanada
  2. 2.Department of MedicineUniversity of TorontoTorontoCanada
  3. 3.Sackler School of MedicineTel-Aviv UniversityTel AvivIsrael
  4. 4.Medicine ABeilinson Hospital, Rabin Medical CenterPetach TikvaIsrael

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