Capecitabine Pattern of Usage, Rate of Febrile Neutropaenia and Treatment Related Death in Asian Cancer Patients in Clinical Practice

  • Phua, Vincent Chee Ee (Clinical Oncology Unit, Faculty of Medicine, University of Malaya) ;
  • Wong, Wei Quan (Jeffrey Cheah School of Medicine and Health Sciences, Monash University) ;
  • Tan, Pei Lin (Pharmacology Department, University Malaya Medical Centre, University of Malaya) ;
  • Bustam, Anita Zarina (Clinical Oncology Unit, Faculty of Medicine, University of Malaya) ;
  • Saad, Marniza (Clinical Oncology Unit, Faculty of Medicine, University of Malaya) ;
  • Alip, Adlinda (Clinical Oncology Unit, Faculty of Medicine, University of Malaya) ;
  • Ishak, Wan Zamaniah Wan (Clinical Oncology Unit, Faculty of Medicine, University of Malaya)
  • Published : 2015.03.09


Background: Oral capecitabine is increasingly replacing intravenous 5-fluorouracil in many chemotherapy regimens. However, data on the risk of febrile neutropaenia (FN) and treatment related death (TRD) with the drug remain sparse outside of clinical trial settings despite its widespread usage. This study aimed to determine these rates in a large cohort of patients treated in the University of Malaya Medical Centre (UMMC). Materials and Methods: We reviewed the clinical notes of all patients prescribed with oral capecitabine chemotherapy for any tumour sites in University Malaya Medical Centre (UMMC) from $1^{st}$ January 2009 till $31^{st}$ June 2010. Information collected included patient demographics, histopathological features, treatment received including the different chemotherapy regimens and intent of treatment whether the chemotherapy was given for neoadjuvant, concurrent with radiation, adjuvant or palliative intent. The aim of this study is to establish the pattern of usage, FN and TRD rates with capecitabine in clinical practice outside of clinical trial setting. FN is defined as an oral temperature > $38.5^{\circ}C$ or two consecutive readings of > $38.0^{\circ}C$ for 2 hours and an absolute neutrophil count < $0.5{\times}10^9/L$, or expected to fall below $0.5{\times}10^9/L$ (de Naurois et al., 2010). Treatment related death was defined as death occurring during or within 30 days of last chemotherapy treatment. Results: Between $1^{st}$ January 2009 and $30^{th}$ June 2010, 274 patients were treated with capecitabine chemotherapy in UMMC. The mean age was 58 years (range 22 to 82 years). Capecitabine was used in 14 different tumour sites with the colorectal site predominating with a total of 128 cases (46.7%), followed by breast cancer (35.8%). Capecitabine was most commonly used in the palliative setting accounting for 63.9% of the cases, followed by the adjuvant setting (19.7%). The most common regimen was single agent capecitabine with 129 cases (47.1%). The other common regimens were XELOX (21.5%) and ECX (10.2%). The main result of this study showed an overall FN rate of 2.2% (6/274). The overall TRD rate was 5.1% (14/274). The FN rate for the single agent capecitabine regimen was 1.6% (2/129) and the TRD rate was 5.4% (7/129). All the TRDs were with single agent capecitabine regimen were used for palliative intent. Conclusions: Oral capecitabine is used widely in clinical practice in a myriad of tumour sites and bears a low risk of febrile neutropaenia. However, capecitabine like any other intravenous chemotherapeutic agent carries a significant risk of treatment related death.


Capecitabine;chemotherapy;febrile neutropaenia;treatment related death


  1. Bilici A, Selcukbiricik F, Demir, et al (2014). Modified docetaxel and cisplatin in combination with capecitabine (DCX) as a first-line treatment in HER2-negative advanced gastric cancer. Asian Pac J Cancer Prev, 15, 8661-6.
  2. Bayoglu IV, Varol U, Yildiz I, et al (2014). Second-Line capecitabine and oxaliplatin combination for gemcitabineresistant advanced pancreatic cancer. Asian Pac J Cancer Prev, 15, 7119-23.
  3. Cassidy J, Twelves C, Van Cutsem E, et al (2002). First-line oral capecitabine therapy in metastatic colorectal cancer: a favorable safety profile compared with intravenous 5-fluorouracil/leucovorin. Ann Oncol, 13, 566-75.
  4. Cassidy J, Clarke S, Diaz-Rubio E, et al (2008). Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol, 26, 2006-12.
  5. Cassidy J, Clarke S, Diaz-Rubio E, et al (2011). XELOX vs FOLFOX-4 as first-line therapy for metastatic colorectal cancer: NO16966 updated results. Br J Cancer, 105, 58-64.
  6. Choi JG, Seo JH, Oh SC, et al (2012). A Phase II Trial of Gemcitabine plus Capecitabine for Patients with Advanced Pancreatic Cancer. Cancer Res Treat, 44, 127-32.
  7. Chua DT, Sham JS, Au GK (2003). A phase II study of capecitabine in patients with recurrent and metastatic nasopharyngeal carcinoma pretreated with platinum-based chemotherapy. Oral Oncol, 39, 361.
  8. Chua D, Wei WI, Sham JS, et al (2008). Capecitabine monotherapy for recurrent and metastatic nasopharyngeal cancer. Jpn J Clin Oncol, 38, 244-9.
  9. Chua DT, Yiu HH, Seetalarom K, et al (2012). Phase II trial of capecitabine plus cisplatin as first-line therapy in patients with metastatic nasopharyngeal cancer. Head Neck, 34, 1225-30.
  10. Chiu J, Tang V, Leung R, et al (2014). Efficacy and tolerability of adjuvant oral capecitabine plus intravenous oxaliplatin (XELOX) in Asian patients with colorectal cancer: 4-year analysis. Asian Pac J Cancer Prev, 14, 6585-90.
  11. Ciuleanu E, Irimie A, Ciuleanu TE, et al (2008). Capecitabine as salvage treatment in relapsed nasopharyngeal carcinoma: a phase II study. J Buon, 13, 37-42.
  12. Comella P, Massidda B, Filippelli G, et al (2009). Randomised trial comparing biweekly oxaliplatin plus oral capecitabine versus oxaliplatin plus i.v. bolus fluorouracil/leucovorin in metastatic colorectal cancer patients: results of the Southern Italy Cooperative Oncology study 0401. J Cancer Res Clin Oncol, 135, 217-26.
  13. Cunningham D, Starling N, Rao S, et al (2008). Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med, 358, 36-46.
  14. de Naurois J, Novitzky-Basso I, Gill MJ, et al (2010). Management of febrile neutropaenia: ESMO clinical practice guidelines. Ann Oncol, 21, 252-6.
  15. Diaz-Rubio E, Tabernero J, Gomez-Espana A, et al (2007). Phase III study of capecitabine plus oxaliplatin compared with continuous-infusion fluorouracil plus oxaliplatin as firstline therapy in metastatic colorectal cancer: final report of the spanish cooperative group for the treatment of digestive tumors trial. J Clin Oncol, 25, 4224-30.
  16. Ducreux M, Bennouna J, Hebbar M, et al (2011). Capecitabine plus oxaliplatin (XELOX) versus 5-fluorouracil/leucovorin plus ox-aliplatin (FOLFOX-6) as first-line treatment for metastatic colorectal cancer. Int J Cancer, 128, 682-90.
  17. Goldberg RM, Sargent DJ, Morton RF, et al (2004). A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol, 22, 23-30.
  18. Jenkins AD, Ramondetta LM, Sun C, et al (2005). Phase II trial of capecitabine in recurrent squamous cell carcinoma of the cervix. Gynecol Oncol, 97, 840-4.
  19. Kang YK, Kang WK, Shin DB, et al (2009). Capecitabine/ cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol, 20, 666-73.
  20. Li YH, Wang FH, Jiang WQ, et al (2008). Phase II study of capecitabine and cisplatin combination as firstline chemotherapy in Chinese patients with metastatic nasopharyngeal carcinoma. Cancer Chemother Pharmacol, 62, 539-44.
  21. Louvet C, Andre T, Tigaud JM, et al (2002). Phase II study of oxaliplatin, fluorouracil, and folinic acid in locally advanced or metastatic gastric cancer patients. J Clin Oncol, 20, 4543-8.
  22. Martinez-Trufero J, Isla D, Adansa JC, et al (2010). Phase II study of capecitabine as palliative treatment for patients with recurrent and metastatic squamous head and neck cancer after previous platinum-based treatment. Br J Cancer, 102, 1687.
  23. Miwa M, Ura M, Nishida M et al (1998). Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue. Eur J Cancer, 34, 1274-81.
  24. Okines AF, Norman AR, McCloud P, et al (2009). Meta-analysis of the REAL-2 and ML17032 trials: evaluating capecitabinebased combination chemotherapy and infused 5-fluorouracilbased combination chemotherapy for the treatment of advanced oesophago-gastric cancer. Ann Oncol, 20, 1529-34.
  25. Rougier P, Mitry E, Cunningham D, et al (2003). Is age a prognostic factor of toxicity and efficacy in patients (pts) with metastatic colorectal cancer (MCRC) receiving irinotecan in combination with 5FU/folinic acid (FA). Proc Am Soc Clin Oncol, 22, 267
  26. Scheithauer W, Mckendrick, Begbie S, et al (2003). Oral capecitabine as an alternative to i.v. 5-fluorouracil-based adjuvant therapy for colon cancer: safety results of a randomized, phase III trial. Ann Oncol, 14, 1735-43.
  27. Stockler MR, Harvey VJ, Francis PA, et al (2011). Capecitabine versus classical cyclophosphamide, methotrexate, and fluorouracil as first-line chemotherapy for advanced breast cancer. J Clin Oncol, 29, 4498-504.
  28. Sym SJ, Chang HM, Ryu MH, et al (2010). Neoadjuvant docetaxel, capecitabine and cisplatin (DXP) in patients with unresectable locally advanced or metastatic gastric cancer. Ann Surg Oncol, 17, 1024-32.
  29. Twelves C, Wong A, Nowacki PN et al (2005). Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med, 352, 2696-704.
  30. Van Cutsem E, Twelves C, Cassidy J, et al (2001). Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol, 19, 4097-106.
  31. Van Cutsem E, Hoff PM, Harper P, et al (2004). Oral capecitabine vs intravenous 5-fluorouracil and leucovorin: integrated efficacy data and novel analyses from two large, randomised, phase III trials. Br J Cancer, 90, 1190-7.
  32. Wadell TS, Chau I, Barbachano Y, et al (2012). A randomized multicenter trial of epirubicin, oxaliplatin, and capecitabine (EOC) plus panitumumab in advanced esophagogastric cancer (REAL3). J Clin Oncol, 30, 18.
  33. Varol U, Dirican A, Yildiz I, et al (2014). First-line monochemotherapy in frail elderly patients with metastatic colorectal cancer. Asian Pac J Cancer Prev, 15, 3157-61.
  34. Vasey PA, McMahon L, Paul J, et al (2003). A phase II trial of capecitabine (Xeloda$^{(R)}$) in recurrent ovarian cancer. British J Cancer, 89, 1843-8.
  35. Xiong HQ, Varadhachary GR, Blais JC, et al (2008). Phase 2 trial of oxaliplatin plus capecitabine (XELOX) as secondline therapy for patients with advanced pancreatic cancer. Cancer, 113, 2046-52.
  36. Yoney A, Isikli L (2013). Can capecitabine be used instead of concurrent bolus 5-FU in postoperative chemoradiotherapy for gastric adenocarcinoma? Asian Pac J Cancer Prev, 14, 5127-31.