The relationship between eGFR and capecitabine efficacy/toxicity in metastatic breast cancer


The objective of this study was to evaluate the efficacy and toxicity of capecitabine in metastatic breast cancer (mBC) according to the estimated glomerular filtration rate (eGFR). A total of 135 patients included in the final analysis were stratified into 3 categories according to baseline eGFR, i.e., eGFR <60 mL/min/1.73 m2 (Group 1), eGFR 60–90 mL/min/1.73 m2 (Group 2) and eGFR >90 mL/min/1.73 m2 (Group 3). If a patient developed a level of toxicity that would lead to capecitabine dose reduction, this was recognized as dose-limiting toxicity (DLT). The dose was reduced due to toxicity in 95 cycles. A total of 95 DLTs were seen in 76 (56.2%) of the 135 patients. When 76 patients with DLT were evaluated according to eGFR, DLT was observed in 93.3% of those in Group 1, 72.5% of those in Group 2 and 41.3% of those in Group 3 (p < 0.001). The median time to progression (TTP) of all patients was 7.4 months. No significant difference in TTP was observed in patients stratified into 3 groups according to eGFR. When the patients were divided into two groups as DLT and without DLT, the median TTP was 8.68 months (95% CI, 7.53–9.81 months) in those with toxicity and 6.23 months (95% CI, 4.04–8.43 months) in those without toxicity (log-rank p = 0.004). We found a significant relationship between low eGFR and increased risk of DLT. Having a DLT was associated with a longer TTP. It indicates the need for more data/larger study investigating these discrepancies.

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  1. 1.

    Al-Batran S-E, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet. 2019;393:1948–57.

    Article  Google Scholar 

  2. 2.

    Masuda N, Lee S-J, Ohtani S, Im Y-H, Lee E-S, Yokota I, et al. Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med. 2017;376:2147–59.

    Article  CAS  Google Scholar 

  3. 3.

    Chen J, Wang X-T, Luo P-H, He Q-J. Effects of unidentified renal insufficiency on the safety and efficacy of chemotherapy for metastatic colorectal cancer patients: a prospective, observational study. Support Care Cancer. 2015;23:1043–8.

    Article  Google Scholar 

  4. 4.

    Poole C, Gardiner J, Twelves C, Johnston P, Harper P, Cassidy J, et al. Effect of renal impairment on the pharmacokinetics and tolerability of capecitabine (Xeloda) in cancer patients. Cancer Chemother Pharmacol. 2002;49:225–34.

    Article  Google Scholar 

  5. 5.

    Daher-Abdi Z, Lavau-Denes S, Prémaud A, Urien S, Sauvage F-L, MARTIN J, et al. Pharmacokinetics and exposure-effect relationships of capecitabine in elderly patients with breast or colorectal cancer. Cancer Chemother Pharmacol. 2014;73:1285–93.

    Article  CAS  Google Scholar 

  6. 6.


  7. 7.

    Bins S, Ratain MJ, Mathijssen RHJ. Conventional dosing of anticancer agents: precisely wrong or just inaccurate? Clin Pharmacol Ther. 2014;95:361–4.

    Article  CAS  Google Scholar 

  8. 8.

    Mathijssen RHJ, de Jong FA, Loos WJ, van der Bol JM, Verweij J, Sparreboom A. Flat-fixed dosing versus body surface area based dosing of anticancer drugs in adults: does it make a difference? Oncologist. 2007;12:913–23.

    Article  Google Scholar 

  9. 9.

    Launay-Vacher V, Janus N, Ray-Coquard IL, Beuzeboc P, Thariat J, Deray G. Overall survival in solid tumor patients with abnormal renal function or renal insufficiency. JCO Am Soc Clin Oncol. 2015;33:1589.

    Article  Google Scholar 

  10. 10.

    Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999;130:461–70.

    Article  CAS  Google Scholar 

  11. 11.

    National Kidney Foundation. KDOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification.

  12. 12.

    Verbraecken J, Van de Heyning P, De Backer W, Van Gaal L. Body surface area in normal-weight, overweight, and obese adults. A comparison study. Metab Clin Exp. 2006;55:515–24.

    Article  CAS  Google Scholar 

  13. 13.

    Launay-Vacher V, Gligorov J, Le Tourneau C, Janus N, Spano J-P, Ray-Coquard I, et al. Prevalence of renal insufficiency in breast cancer patients and related pharmacological issues. Breast Cancer Res Treat. 2010;124:745–53.

    Article  CAS  Google Scholar 

  14. 14.

    Hudis C, Traina T, Norton L. Capecitabine dosing is not yet optimized for breast cancer. Ann Oncol. 2010;21:2291.

    Article  CAS  Google Scholar 

  15. 15.

    Ilich AI, Danilak M, Kim CA, Mulder KE, Spratlin JL, Ghosh S, et al. Effects of gender on capecitabine toxicity in colorectal cancer. J Oncol Pharm Pract. 2016;22:454–60.

    Article  CAS  Google Scholar 

  16. 16.

    Miller KD, Chap LI, Holmes FA, Cobleigh MA, Marcom PK, Fehrenbacher L, et al. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. JCO. 2005;23:792–9.

    Article  CAS  Google Scholar 

  17. 17.

    Nishijima TF, Suzuki M, Muss HB. A comparison of toxicity profiles between the lower and standard dose capecitabine in breast cancer: a systematic review and meta-analysis. Breast Cancer Res Treat. 2016;156:227–36.

    Article  CAS  Google Scholar 

  18. 18.

    Cadoo KA, Gajria D, Suh E, Patil S, Theodoulou M, Norton L, et al. Decreased gastrointestinal toxicity associated with a novel capecitabine schedule (7 days on and 7 days off): a systematic review. NPJ Breast Cancer. 2016;2:1–5.

    Article  Google Scholar 

  19. 19.

    Leonard R, Hennessy BT, Blum JL, O’Shaughnessy J. Dose-adjusting capecitabine minimizes adverse effects while maintaining efficacy: a retrospective review of capecitabine for metastatic breast cancer. Clin Breast Cancer. 2011;11:349–56.

    Article  CAS  Google Scholar 

  20. 20.

    Kaufmann M, Maass N, Costa SD, Schneeweiß A, Loibl S, Sütterlin MW, et al. First-line therapy with moderate dose capecitabine in metastatic breast cancer is safe and active: results of the MONICA trial. Eur J Cancer. 2010;46:3184–91.

    Article  CAS  Google Scholar 

  21. 21.

    Naughton M. Evolution of Capecitabine dosing in breast cancer. Clin Breast Cancer. 2010;10:130–5.

    Article  CAS  Google Scholar 

  22. 22.

    Prado CMM, Baracos VE, McCargar LJ, Reiman T, Mourtzakis M, Tonkin K, et al. Sarcopenia as a determinant of chemotherapy toxicity and time to tumor progression in metastatic breast cancer patients receiving capecitabine treatment. Clin Cancer Res. 2009;15:2920–6.

    Article  CAS  Google Scholar 

  23. 23.

    Prado CM, Lieffers JR, McCargar LJ, Reiman T, Sawyer MB, Martin L, et al. Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol. 2008;9:629–35.

    Article  Google Scholar 

  24. 24.

    Lichtman SM, Cirrincione CT, Hurria A, Jatoi A, Theodoulou M, Wolff AC, et al. Effect of pretreatment renal function on treatment and clinical outcomes in the adjuvant treatment of older women with breast cancer: alliance A171201, an ancillary study of CALGB/CTSU 49907. J Clin Oncol. 2016;34:699–705.

    Article  CAS  Google Scholar 

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The authors declared that this study has received no financial support.

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All authors have made substantial contributions to the conception and design, acquisition, analysis and interpretation of the data in this study. All have also been involved in drafting the manuscript or revising it critically for important intellectual content and all have given final approval of the version to be published.

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Correspondence to Emir Celik.

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All authors declare that the research was conducted according to the principles of the World Medical Association Declaration of Helsinki “Ethical Principles for Medical Research Involving Human Subjects.” Data collection and analysis of all subjects was approved by the ethics committee of the study area.

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Celik, E., Samanci, N.S., Karadag, M. et al. The relationship between eGFR and capecitabine efficacy/toxicity in metastatic breast cancer. Med Oncol 38, 11 (2021).

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  • Breast cancer
  • Renal insufficiency
  • Capecitabine
  • Toxicity