Clinical and Translational Oncology

, Volume 14, Issue 9, pp 689–697

Incidence of hand–foot syndrome with capecitabine in combination with chemotherapy as first-line treatment in patients with advanced and/or metastatic gastric cancer suitable for treatment with a fluoropyrimidine-based regimen

  • Carlos Gómez-Martin
  • Antonio Sánchez
  • Antonio Irigoyen
  • Beatriz Llorente
  • Begoña Pérez
  • Raquel Serrano
  • Mª José Safont
  • Esther Falcó
  • Adelaida Lacasta
  • Margarita Reboredo
  • Jorge Aparicio
  • Rosario Dueñas
  • Marta Llanos Muñoz
  • Pilar Regueiro
  • Elena Sanchez-Viñes
  • Rafael López López
Research Article



Hand–foot syndrome (HFS) is a limiting toxicity of capecitabine, which is not life-threatening but could compromise capecitabine efficacy.

Materials and methods

This phase II, multicenter, non-controlled study assessed the safety, particularly grade three HFS incidence, and efficacy of four capecitabine-based chemotherapy regimens [cisplatin/capecitabine (CX), epirubicin/cisplatin/capecitabine (ECX), epirubicin/oxaliplatin/capecitabine (EOX) and docetaxel/cisplatin/capecitabine (DCX)] as first-line treatment for advanced and/or metastatic gastric cancer.


One hundred and eight patients were assigned to one of the four treatment groups, according to investigator’s criteria, and grouped together for both safety and efficacy primary analyses. HFS was reported in 31 patients (19.6 %) and its first presentation occurred at a median of 72 days (range 19–209 days). Grade 3 HFS developed in 6.3, 5.2, 3.7 and 2.4 %, of patients receiving ECX, DCX, EOX or CX chemotherapy regimen, respectively. Capecitabine dose reduction/discontinuation due to HFS was required in 5.7 % of patients (9/158). The most common (>10 %) grade 3–4 treatment-related AEs were neutropenia (15.2 %), asthenia (12.0 %) and diarrhoea (11.4 %).


A moderate incidence of HFS was reported in patients treated with capecitabine, which generally presented late and required dose reduction in <1/3 of patients. The results suggest that capecitabine may be useful in combination with standard fluorouracil-based regimens in patients with advanced and/or metastatic gastric cancer with favourable safety profile.


Capecitabine stomach neoplasms Neoplasm metastasis Fluorouracil Foot dermatoses/chemically induced Hand dermatoses/chemically induced 


  1. 1.
    Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127(12):2893–2917PubMedCrossRefGoogle Scholar
  2. 2.
    Cabanes A, Perez-Gomez B, Aragones N, Pollan M, Lopez-Abente G (2009) La situación del cáncer en España, 1975–2006. INE-MadridGoogle Scholar
  3. 3.
    Altekruse SF, Kosary CL, Krapcho M et al (2011) SEER cancer statistics review, 1975–2007, National Cancer Institute. Bethesda, MD., based on November 2009 SEER data submission, posted to the SEER web site, 2010
  4. 4.
    Hendlisz A, Bleiberg H (1995) Diagnosis and treatment of gastric cancer. Drugs 49(5):711–720PubMedCrossRefGoogle Scholar
  5. 5.
    Schipper DL, Wagener DJ (1996) Chemotherapy of gastric cancer. Anticancer Drugs 7(2):137–149PubMedCrossRefGoogle Scholar
  6. 6.
    Lacave AJ, Baron FJ, Anton LM et al (1991) Combination chemotherapy with cisplatin and 5-fluorouracil 5-day infusion in the therapy of advanced gastric cancer: a phase II trial. Ann Oncol 2(10):751–754PubMedGoogle Scholar
  7. 7.
    Kim NK, Park YS, Heo DS et al (1993) A phase III randomized study of 5-fluorouracil and cisplatin versus 5-fluorouracil, doxorubicin, and mitomycin C versus 5-fluorouracil alone in the treatment of advanced gastric cancer. Cancer 71(12):3813–3818PubMedCrossRefGoogle Scholar
  8. 8.
    Webb A, Cunningham D, Scarffe JH et al (1997) Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. J Clin Oncol 15(1):261–267PubMedGoogle Scholar
  9. 9.
    Van Cutsem E, Moiseyenko VM, Tjulandin S et al (2006) Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol 24(31):4991–4997PubMedCrossRefGoogle Scholar
  10. 10.
    Hong YS, Song SY, Lee SI et al (2004) A phase II trial of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer. Ann Oncol 15(9):1344–1347PubMedCrossRefGoogle Scholar
  11. 11.
    Koizumi W, Saigenji K, Ujiie S, Terashima M, Sakata Y, Taguchi T (2003) A pilot phase II study of capecitabine in advanced or recurrent gastric cancer. Oncology 64(3):232–236PubMedCrossRefGoogle Scholar
  12. 12.
    Sakamoto J, Chin K, Kondo K et al (2006) Phase II study of a 4-week capecitabine regimen in advanced or recurrent gastric cancer. Anticancer Drugs 17(2):231–236PubMedCrossRefGoogle Scholar
  13. 13.
    Kim TW, Kang YK, Ahn JH et al (2002) Phase II study of capecitabine plus cisplatin as first-line chemotherapy in advanced gastric cancer. Ann Oncol 13(12):1893–1898PubMedCrossRefGoogle Scholar
  14. 14.
    Lee J, Im YH, Cho EY et al (2008) A phase II study of capecitabine and cisplatin (XP) as first-line chemotherapy in patients with advanced esophageal squamous cell carcinoma. Cancer Chemother Pharmacol 62(1):77–84PubMedCrossRefGoogle Scholar
  15. 15.
    Kang YK, Ryu MH, Yoo C et al (2011) Phase I/II study of a combination of docetaxel, capecitabine, and cisplatin (DXP) as first-line chemotherapy in patients with advanced gastric cancer. Cancer Chemother Pharmacol 67(6):1435–1443PubMedCrossRefGoogle Scholar
  16. 16.
    Cunningham D, Starling N, Rao S et al (2008) Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med 358(1):36–46PubMedCrossRefGoogle Scholar
  17. 17.
    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(4):666–673PubMedCrossRefGoogle Scholar
  18. 18.
    National Institute for Health and Clinical Excellence (2010) Capecitabine for the treatment of advanced gastric cancer. NICE technology appraisal guidance 191 Accessed 19 Jan 2011
  19. 19.
    Webster-Gandy JD, How C, Harrold K (2007) Palmar-plantar erythrodysesthesia (PPE): a literature review with commentary on experience in a cancer centre. Eur J Oncol Nurs 11(3):238–246PubMedCrossRefGoogle Scholar
  20. 20.
    Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European organization for research and treatment of cancer, national cancer institute of the United States, national cancer institute of Canada. J Natl Cancer Inst 92(3):205–216PubMedCrossRefGoogle Scholar
  21. 21.
    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(21):4097–4106PubMedGoogle Scholar
  22. 22.
    Nagore E, Insa A, Sanmartin O (2000) Antineoplastic therapy-induced palmar plantar erythrodysesthesia (‘hand–foot’) syndrome. Incidence, recognition and management. Am J Clin Dermatol 1(4):225–234PubMedCrossRefGoogle Scholar
  23. 23.
    Abushullaih S, Saad ED, Munsell M, Hoff PM (2002) Incidence and severity of hand–foot syndrome in colorectal cancer patients treated with capecitabine: a single-institution experience. Cancer Invest 20(1):3–10PubMedCrossRefGoogle Scholar
  24. 24.
    Capecitabine -SPC (2010) Xeloda (capecitabine)–Roche Pharma AG. Summary of Product CharacteristicsGoogle Scholar
  25. 25.
    Oxaliplatin-SPC (2010) Oxaliplatin. Summary of Product CharacteristicsGoogle Scholar
  26. 26.
    Epirubicin-SPC (2010) Epirubicin. Summary of Product CharacteristicsGoogle Scholar
  27. 27.
    Martinez Amores B, Alsina M, Jiménez E et al (2011) Observational transversal study to relate functional status and age with the doublet or triplet chemotherapy based on capecitabine in advanced gastric cancer patients. J Clin Oncol 29: (suppl 4), abstract 59Google Scholar

Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2012

Authors and Affiliations

  • Carlos Gómez-Martin
    • 1
    • 16
  • Antonio Sánchez
    • 2
  • Antonio Irigoyen
    • 3
  • Beatriz Llorente
    • 4
  • Begoña Pérez
    • 5
  • Raquel Serrano
    • 6
  • Mª José Safont
    • 7
  • Esther Falcó
    • 8
  • Adelaida Lacasta
    • 9
  • Margarita Reboredo
    • 10
  • Jorge Aparicio
    • 11
  • Rosario Dueñas
    • 12
  • Marta Llanos Muñoz
    • 13
  • Pilar Regueiro
    • 14
  • Elena Sanchez-Viñes
    • 14
  • Rafael López López
    • 15
  1. 1.Gastrointestinal Cancer Unit, Medical Oncology DivisionDoce de Octubre University HospitalMadridSpain
  2. 2.Oncology DepartmentPuerta de Hierro University HospitalMadridSpain
  3. 3.Oncology DepartmentVirgen de las Nieves HospitalGranadaSpain
  4. 4.Medical Oncology DepartmentGeneral Yagüe HospitalBurgosSpain
  5. 5.Oncology DepartmentVirgen del Rocío HospitalSevillaSpain
  6. 6.Oncology DepartmentReina Sofía HospitalCórdobaSpain
  7. 7.Oncology DepartmentGeneral Hospital of ValenciaValenciaSpain
  8. 8.Oncology DepartmentSon Llatzer HospitalPalma de MallorcaSpain
  9. 9.Oncology DepartmentDonostia HospitalDonostiaSpain
  10. 10.Oncology DepartmentJuan Canalejo HospitalA CoruñaSpain
  11. 11.Oncology DepartmentLa Fé HospitalValenciaSpain
  12. 12.Oncology DepartmentHospital of JaenJaenSpain
  13. 13.Oncology DepartmentUniversity Hospital of CanariasSanta Cruz de TenerifeSpain
  14. 14.Medical DepartmentRoche FarmaMadridSpain
  15. 15.Oncology DepartmentComplejo Hospitalario Universitario of SantiagoSantiago de CompostelaSpain
  16. 16.Gastrointestinal Cancer Clinical Research Unit, Clinical Research ProgrammeSpanish National Câncer Research Centre (CNIO), Fuenlabrada University HospitalMadridSpain

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