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Survival outcome and prognostic model of patients with colorectal cancer on phase 1 trials

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Summary

Background Patients with metastatic colorectal cancer (mCRC) who progress on standard therapies may be eligible for phase I trials. To better delineate the risk-benefit ratio, we assessed toxicities, clinical outcomes and prognostic factors. Methods Records of mCRC patients on phase I trials at our institution over 18 years were reviewed. Univariable (UVA) and multivariable analyses (MVA) were undertaken and a prognostic model developed. Results There were 187 enrollments on 37 phase I trials. Median age was: 59 (29–83) years and number of prior therapies: 3 (0–8). The clinical benefit rate (CBR): response (5.6%) + stable disease, was 43.1%. Median progression free survival (PFS) and overall survival (OS) was 7.7 weeks and 43.7 weeks, respectively. The MVA identified age > 60 years (HR 1.63, p < 0.004), albumin<3.5 g/dL (HR 3.69, p < 0.001), direct bilirubin>ULN (HR1.69, p < 0.01), and WBC ≥ 5.2 k/uL (HR 1.97, p < 0.001) as negative prognostic factors. A risk score based on the MVA revealed that patients with a score of 0–1 had an improved OS (58.7 weeks) compared to a score of 2 (49.9 weeks, p < 0.01) and 3 (14.1 weeks, p < 0.001). Conclusions Phase 1 trials may offer similar or better clinical outcome for mCRC patients than standard third line therapies; the prognostic model could assist in selecting appropriate patients.

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Authors and Affiliations

  1. Montefiore Medical Center, 1695 Eastchester Road, Bronx, NY, 10461, USA

    Audrey E. Kam, Umang H. Shah, Mohammad H. Ghalib, Imran Chaudhary, Jennifer Chuy, Lakshmi Rajdev, Andreas Kaubisch, Santiago Aparo, Ioannis Mantzaris & Sanjay Goel

  2. Jacobi Medical Center, 1400 Pelham Pkwy S, Bronx, NY, 10461, USA

    Gopichand Pendurti

  3. Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461, USA

    Gopichand Pendurti, Jennifer Chuy, Lakshmi Rajdev, Andreas Kaubisch, Santiago Aparo, Ioannis Mantzaris & Sanjay Goel

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  1. Audrey E. Kam
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Correspondence to Sanjay Goel.

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Conflict of interest

The authors declare no conflict of interest.

Ethical approval

Each individual clinical trial from which data was extracted was approved by the ethics committee of Montefiore Medical Center. Each individual trial was performed in accordance with the 1964 Helsinki declaration and its later amendments.

Informed consent

All patients entering the clinical trials have signed the informed consent document.

Electronic supplementary material

Supplementary Table A1

(DOC 41 kb)

Summary of hematologic and nonhematologic toxicities of patients on phase 1 trials. Grading of toxicity based on CTCAE version at the time of study entry. Abbreviations: CTCAE = Common Terminology Criteria for Adverse Events.

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Kam, A.E., Pendurti, G., Shah, U.H. et al. Survival outcome and prognostic model of patients with colorectal cancer on phase 1 trials. Invest New Drugs 37, 490–497 (2019). https://doi.org/10.1007/s10637-018-0675-9

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  • DOI: https://doi.org/10.1007/s10637-018-0675-9

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