Skip to main content

Predictors of toxicity-related hospitalization in four randomized studies of 5-fluorouracil-based chemotherapy in metastatic colorectal cancer

Abstract

Objective

To evaluate the predictors of toxicity-related hospitalization associated with various chemotherapy regimens among metastatic colorectal cancer patients

Methods

This pooled analysis includes patient-level datasets from four randomized clinical studies (NCT00272051; NCT00305188; NCT00115765; NCT00364013). Through univariate and multivariate logistic regression analyses, factors predicting the development of serious adverse events, fatal adverse events, and toxicity-related hospitalizations were determined.

Results

A total of 2533 patients were included in the current study. A total of 1010 patients (39.9%) experienced one or more episodes of serious adverse events. These include 914 patients (36.1%) who were hospitalized at least once and 148 patients (5.8%) who suffered from a fatal adverse event. Within multivariate logistic regression analysis, older age (P < 0.001), higher ECOG score (P < 0.001), bevacizumab-containing chemotherapy (P < 0.001), and panitumumab-containing chemotherapy (P < 0.001) were predictive of hospitalization. Similarly, older age (P < 0.001), higher ECOG score (P < 0.001), and panitumumab-containing chemotherapy (P = 0.003) were predictive of fatal adverse events in multivariate logistic regression analysis. Moreover, in a multivariate Cox regression analysis, hospitalization was predictive of worse overall survival (P < 0.001) and progression-free survival (P < 0.001).

Conclusions

Older age, poorer performance status, and bevacizumab- and panitumumab-containing regimens are associated with a higher risk of hospitalization. Moreover, hospitalization is predictive of worse overall and progression-free survival.

This is a preview of subscription content, access via your institution.

References

  1. 1.

    Numico G, Cristofano A, Mozzicafreddo A, Cursio OE, Franco P, Courthod G, Trogu A, Malossi A, Cucchi M, Sirotovà Z, Alvaro MR, Stella A, Grasso F, Spinazzé S, Silvestris N (2015) Hospital admission of cancer patients: avoidable practice or necessary care? PLoS One 10(3):e0120827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Brooks GA, Abrams TA, Meyerhardt JA, Enzinger PC, Sommer K, Dalby CK, Uno H, Jacobson JO, Fuchs CS, Schrag D (2014) Identification of potentially avoidable hospitalizations in patients with GI cancer. J Clin Oncol 32(6):496–503

    Article  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Russo CA, Stocks C (2006) Hospitalizations for colorectal cancer, 2006: Statistical Brief #69. 2009 Mar. In: Healthcare Cost and Utilization Project (HCUP) Statistical Briefs [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US). Available from: https://www.ncbi.nlm.nih.gov/books/NBK54563/. Accessed 10 Jan 2018

  4. 4.

    Oster G (1999) Hospitalization for 5-FU toxicity in metastatic colorectal cancer: incidence and cost. Oncology (Williston Park, NY) 13(7 Suppl 3):41

    CAS  Google Scholar 

  5. 5.

    Devani K, Patil N, Simons-Linares CR, Patel N, Jaiswal P, Patel P, Patel S, Savani C, Sajnani K, Young M, Reddy C (2017) Trends in hospitalization and mortality of venous thromboembolism in hospitalized patients with colon cancer and their outcomes: US perspective. Clin Colorectal Cancer 16(3):e199–e204

    Article  PubMed  Google Scholar 

  6. 6.

    https://www.projectdatasphere.org/projectdatasphere/html/home. Last accessed on 7/10/2017

  7. 7.

    globocan.iarc.fr. Last accessed on 27/11/2016

  8. 8.

    Labianca R, Nordlinger B, Beretta GD, Mosconi S, Mandala M, Cervantes A et al (2013) Early colon cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 24(Suppl 6):vi64–vi72

    Article  PubMed  Google Scholar 

  9. 9.

    Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Błasińska-Morawiec M, Šmakal M, Canon JL, Rother M, Oliner KS, Tian Y, Xu F, Sidhu R (2014) Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer. Ann Oncol 25(7):1346–1355

    Article  CAS  PubMed  Google Scholar 

  10. 10.

    Hecht JR, Mitchell E, Chidiac T, Scroggin C, Hagenstad C, Spigel D, Marshall J, Cohn A, McCollum D, Stella P, Deeter R, Shahin S, Amado RG (2009) A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J Clin Oncol 27(5):672–680

    Article  CAS  PubMed  Google Scholar 

  11. 11.

    https://www.fda.gov/safety/medwatch/howtoreport/ucm053087.htm. Last accessed on 7/10/2018

  12. 12.

    Bansal P, Rabinowitz I, Boumber Y, Bansal D (2017) Cost of colon cancer care: results of nationwide inpatient sample (NIS) data. J Clin Oncol 35(4_suppl):692

    Article  Google Scholar 

Download references

Acknowledgments

This publication is based on research using information obtained from www.projectdatasphere.org.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Omar Abdel-Rahman.

Ethics declarations

Informed consent

Informed consent was obtained from all participants included in the study.

Ethical approval

All procedures performed were in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Abdel-Rahman, O., Ahmed, O. Predictors of toxicity-related hospitalization in four randomized studies of 5-fluorouracil-based chemotherapy in metastatic colorectal cancer. Int J Colorectal Dis 34, 675–680 (2019). https://doi.org/10.1007/s00384-019-03252-y

Download citation

Keywords

  • 5-fluorouracil
  • Serious adverse events
  • Fatal adverse events
  • Hospitalization
  • Colorectal cancer