Skip to main content

Advertisement

SpringerLink
Log in

Prevalence of hand-foot syndrome following chemotherapy for colorectal cancer: a systematic review and meta-analysis

  • RESEARCH
  • Published:
International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Objective

To systematically evaluate the prevalence of hand-foot syndrome (HFS) in patients with colorectal cancer undergoing chemotherapy.

Methods

The PubMed, Embase, and Cochrane Library databases were searched, from their inception to September 20, 2022, to identify studies on the prevalence of HFS in patients with colorectal cancer receiving chemotherapy. Comprehensive retrieval of literature was performed using the literature tracing method. We calculated the prevalence of HFS in patients with colorectal cancer undergoing chemotherapy based on meta-analyses. Subgroup analysis and meta-regression analyses were performed to determine the sources of heterogeneity.

Results

A total of 20 studies were included, involving 4773 cases. Meta-analysis of the random effects model showed that the total prevalence of HFS in patients with colorectal cancer undergoing chemotherapy was 49.1% (95% confidence interval [CI]: 0.332, 0.651). Subgroup analysis demonstrated that the most frequent grades of HFS were grades 1 and 2, accounting for 40.1% (95% CI: 0.285, 0.523) of cases; this rate was markedly higher than that of grades 3 and 4 (5.8%; 95% CI: 0.020, 0.112). The meta-regression results illustrated that the type of research, country of the study population, type of drug, and year of publication were not sources of heterogeneity in this setting (P > 0.05).

Conclusion

The present findings showed that the prevalence of HFS in patients with colorectal cancer receiving chemotherapy was high. Healthcare professionals should provide knowledge to such patients regarding the prevention and management of HFS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Santucci C, Carioli G, Bertuccio P, Malvezzi M, Pastorino U, Boffetta P, Negri E, Bosetti C, La Vecchia C (2020) Progress in cancer mortality, incidence, and survival: a global overview. European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (ECP) 29(5):367–381

    Article  PubMed  Google Scholar 

  2. Lotfollahzadeh S, Recio-Boiles A, Cagir B (2022) Colon cancer. In: StatPearls. edn. Treasure Island (FL): StatPearls Publishing Copyright © 2022, StatPearls Publishing LLC 3

  3. Siegel RL, Miller KD, Fuchs HE, Jemal A (2022) Cancer statistics, 2022. CA Cancer J Clin 72(1):7–33

    Article  PubMed  Google Scholar 

  4. Pomeroy AE, Schmidt EV, Sorger PK, Palmer AC (2022) Drug independence and the curability of cancer by combination chemotherapy. Trends Cancer 8(11):915–929

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Yap YS, Kwok LL, Syn N, Chay WY, Chia JWK, Tham CK, Wong NS, Lo SK, Dent RA, Tan S et al (2017) Predictors of hand-foot syndrome and pyridoxine for prevention of capecitabine-induced hand-foot syndrome: a randomized clinical trial. JAMA Oncol 3(11):1538–1545

    Article  PubMed  PubMed Central  Google Scholar 

  6. Lu W, Huang Z, Chen S, Lv H, Chen X, Lei J, Ke C, Hong C, Wei Y, Su R et al (2021) The effectiveness of EVOSKIN®Palm and sole moisturizing cream in treating capecitabine-associated hand-foot syndrome: a randomized double-blind clinical trial. Ann Palliat Med 10(3):3009–3017

    Article  PubMed  Google Scholar 

  7. Kwakman JJM, Simkens LHJ, van Rooijen JM, van de Wouw AJ, Ten Tije AJ, Creemers GJM, Hendriks MP, Los M, van Alphen RJ, Polée MB et al (2017) Randomized phase III trial of S-1 versus capecitabine in the first-line treatment of metastatic colorectal cancer: SALTO study by the Dutch Colorectal Cancer Group. Annals of Oncology : Official Journal of the European Society for Medical Oncology 28(6):1288–1293

    Article  CAS  PubMed  Google Scholar 

  8. Simkens LH, van Tinteren H, May A, ten Tije AJ, Creemers GJ, Loosveld OJ, de Jongh FE, Erdkamp FL, Erjavec Z, van der Torren AM et al (2015) Maintenance treatment with capecitabine and bevacizumab in metastatic colorectal cancer (CAIRO3): a phase 3 randomised controlled trial of the Dutch Colorectal Cancer Group. Lancet 385(9980):1843–1852

    Article  CAS  PubMed  Google Scholar 

  9. Zhao Y, Ding Y, Lu Y, Zhang J, Gu J, Li M (2013) Incidence and self-management of hand-foot syndrome in patients with colorectal cancer. Clin J Oncol Nurs 17(4):434–437

    Article  PubMed  Google Scholar 

  10. Son HS, Lee WY, Lee WS, Yun SH, Chun HK (2009) Compliance and effective management of the hand-foot syndrome in colon cancer patients receiving capecitabine as adjuvant chemotherapy. Yonsei Med J 50(6):796–802

    Article  PubMed  PubMed Central  Google Scholar 

  11. Munn Z, Moola S, Lisy K, Riitano D, Tufanaru C (2015) Methodological guidance for systematic reviews of observational epidemiological studies reporting prevalence and cumulative incidence data. Int J Evid Based Healthc 13(3):147–153

    Article  PubMed  Google Scholar 

  12. Wu J, Wang Z, Jin C, Ren H, Hu Y, Yang B, Hu Y (2021) Effect of cetuximab combined with chemotherapy in treating metastatic colorectal cancer and its prognostic analysis. J BUON 26(1):101–108

    PubMed  Google Scholar 

  13. Pietrantonio F, Lobefaro R, Antista M, Lonardi S, Raimondi A, Morano F, Mosconi S, Rimassa L, Murgioni S, Sartore-Bianchi A et al (2020) Capecitabine and temozolomide versus FOLFIRI in RAS-mutated, MGMT-methylated metastatic colorectal cancer. Clin Cancer Res 26(5):1017–1024

    Article  CAS  PubMed  Google Scholar 

  14. Mizumoto Y, Yokoyama S, Matsuda K, Iwamoto H, Mitani Y, Tamura K, Nakamura Y, Murakami D, Oka M, Kobayashi Y et al (2020) Modulation of capecitabine administration to improve continuity of adjuvant chemotherapy for patients with colorectal cancer: a phase II study. Mol Clin Oncol 12(2):126–133

    CAS  PubMed  Google Scholar 

  15. Guo Y, Zheng T, Zhang C, Zhang Y (2020) A study of the S-1 or capecitabine as first-line regimen in patients with metastatic colorectal cancer: a real world study. J Cancer 11(7):1839–1845

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Yamazaki K, Matsumoto S, Imamura CK, Yamagiwa C, Shimizu A, Yoshino T (2019) Clinical impact of baseline renal function on safety and early discontinuation of adjuvant capecitabine plus oxaliplatin in elderly patients with resected colon cancer: a multicenter post-marketing surveillance study. Jpn J Clin Oncol 50(2):122–128

    Google Scholar 

  17. Xu JL, Tang CW, Feng WM, Bao Y, Chai ZZ (2019) Prolonged capecitabine chemotherapy following capecitabine and oxaliplatin (CAPOX) regimen chemotherapy failed to improve survival of stage III colorectal cancer after radical resection. Medical Science Monitor : International Medical Journal of Experimental and Clinical Research 25:4831–4836

    Article  CAS  PubMed  Google Scholar 

  18. Sánchez-Gundín J, Torres-Suárez AI, Fernández-Carballido AM, Barreda-Hernández D (2019) Capecitabine safety profile, innovative and generic adjuvant formulation of nonmetastatic colorectal cancer. Farmacia hospitalaria : organo oficial de expresion cientifica de la Sociedad Espanola de Farmacia Hospitalaria 43(5):158–162

    PubMed  Google Scholar 

  19. Lu CX, Zheng BW, Bai B, Hu JL, Fan SF, Shang DF, Yang D, Zhao CL, Cang SD (2019) Effect of omeprazole on plasma concentration and adverse reactions of capecitabine in patients with colon cancer. Zhonghua zhong liu za zhi [Chinese journal of oncology] 41(9):708–711

    CAS  PubMed  Google Scholar 

  20. Suenaga M, Akiyoshi T, Shinozaki E, Fujimoto Y, Matsusaka S, Konishi T, Nagayama S, Fukunaga Y, Kawakami K, Yokokawa T et al (2018) A feasibility study of capecitabine and oxaliplatin for patients with stage II/III colon cancer -ACTOR study. Anticancer Res 38(3):1741–1747

    CAS  PubMed  Google Scholar 

  21. Peng J, Li W, Zhang R, Lin J, Tang J, Wen Y, Lu Z, Wu X, Pan Z (2019) Safety and efficacy of a modified XELOX adjuvant regimen for patients with operated stage III colon cancer: a Chinese single-center experience. Cancer Commun 39(1)

  22. Kusumoto T, Sunami E, Ota M, Yoshida K, Sakamoto Y, Tomita N, Maeda A, Mochizuki I, Okabe M, Kunieda K et al (2018) Planned safety analysis of the ACTS-CC 02 trial: a randomized phase III trial of S-1 with oxaliplatin versus tegafur and uracil with leucovorin as adjuvant chemotherapy for high-risk stage III colon cancer. Clin Colorectal Cancer 17(2):e153–e161

    Article  PubMed  Google Scholar 

  23. Suto T, Ishiguro M, Hamada C, Kunieda K, Masuko H, Kondo K, Ishida H, Nishimura G, Sasaki K, Morita T et al (2017) Preplanned safety analysis of the JFMC37-0801 trial: a randomized phase III study of six months versus twelve months of capecitabine as adjuvant chemotherapy for stage III colon cancer. Int J Clin Oncol 22(3):494–504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Emi Y, Kakeji Y, Oki E, Saeki H, Ando K, Kitazono M, Sakaguchi Y, Morita M, Samura H, Ogata Y et al (2013) Initial report of KSCC0803: feasibility study of capecitabine as adjuvant chemotherapy for stage III colon cancer in Japanese patients. Int J Clin Oncol 18(2):254–259

    Article  CAS  PubMed  Google Scholar 

  25. Hong YS, Park YS, Lim HY, Lee J, Kim TW, Kim KP, Kim SY, Baek JY, Kim JH, Lee KW et al (2012) S-1 plus oxaliplatin versus capecitabine plus oxaliplatin for first-line treatment of patients with metastatic colorectal cancer: a randomised, non-inferiority phase 3 trial. Lancet Oncol 13(11):1125–1132

    Article  CAS  PubMed  Google Scholar 

  26. Law CC, Fu YT, Chau KK, Choy TS, So PF, Wong KH (2007) Toxicity profile and efficacy of oral capecitabine as adjuvant chemotherapy for Chinese patients with stage III colon cancer. Dis Colon Rectum 50(12):2180–2187

    Article  PubMed  Google Scholar 

  27. Bajetta E, Di Bartolomeo M, Mariani L, Cassata A, Artale S, Frustaci S, Pinotti G, Bonetti A, Carreca I, Biasco G et al (2004) Randomized multicenter phase II trial of two different schedules of irinotecan combined with capecitabine as first-line treatment in metastatic colorectal carcinoma. Cancer 100(2):279–287

    Article  CAS  PubMed  Google Scholar 

  28. 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):3–10

    Article  CAS  PubMed  Google Scholar 

  29. Chiara S, Nobile MT, Barzacchi C, Sanguineti O, Vincenti M, Di Somma C, Meszaros P, Rosso R (1997) Hand-foot syndrome induced by high-dose, short-term, continuous 5-fluorouracil infusion. Eur J Cancer 33(6):967–969

    Article  CAS  PubMed  Google Scholar 

  30. Nakamura N, Shiraiwa H, Haruna Y, Ichijima T, Takeda T, Hasegawa K, Kusumoto M, Yano Y (2021) Effectiveness of protocol-based pharmacotherapy management collaboration between hospital and community pharmacists to address capecitabine-related hand–foot syndrome in cancer patients: a retrospective study. J Pharm Health Care Sci 7(1)

  31. Chen J, Wang B, Yin X, Liang Q, Li Y, Xie X, Zeng X (2022) Application value of nutrition support team in chemotherapy period of colon cancer based on internet multidisciplinary treatment mode. Comput Math Methods Med 2022

  32. Ye JX, Liu AQ, Ge LY, Zhou SZ, Liang ZG (2014) Effectiveness and safety profile of S-1-based chemotherapy compared with capecitabine-based chemotherapy for advanced gastric and colorectal cancer: a meta-analysis. Exp Ther Med 7(5):1271–1278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Punt CJA, Kwakman JJM, Mol L (2022) Long-term safety data on S-1 administered after previous intolerance to capecitabine-containing systemic treatment for metastatic colorectal cancer. Clin Colorectal Cancer 21(3):229–235

    Article  PubMed  Google Scholar 

  34. Xu J, Lin Z, Chen J, Zhang J, Li W, Zhang R, Xing J, Ye Z, Liu X, Gao Q et al (2022) Milk and egg are risk factors for adverse effects of capecitabine-based chemotherapy in Chinese colorectal cancer patients. Integr Cancer Ther 21:15347354221105484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Jiang M, Ding G, Li G (2021) Diagnostic value of combined detection of multiple tumor markers and blood lipid indexes in colorectal cancer and its prediction on adverse reactions of chemotherapy. J BUON 26(4):1226–1230

    PubMed  Google Scholar 

  36. Baack BR, Burgdorf WH (1991) Chemotherapy-induced acral erythema. J Am Acad Dermatol 24(3):457–461

    Article  CAS  PubMed  Google Scholar 

  37. Tsuboi H, Yonemoto K, Katsuoka K (2005) A case of bleomycin-induced acral erythema (AE) with eccrine squamous syringometaplasia (ESS) and summary of reports of AE with ESS in the literature. J Dermatol 32(11):921–925

    Article  PubMed  Google Scholar 

  38. Yoshida Y, Sasaoka S, Tanaka M, Matsumoto K, Inoue M, Satake R, Shimada K, Mukai R, Suzuki T, Iwata M et al (2022) Analysis of drug-induced hand-foot syndrome using a spontaneous reporting system database. Ther Adv Drug saf 13:20420986221101964

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Murugan K, Ostwal V, Carvalho MD, D’Souza A, Achrekar MS, Govindarajan S, Gupta S (2016) Self-identification and management of hand-foot syndrome (HFS): effect of a structured teaching program on patients receiving capecitabine-based chemotherapy for colon cancer. Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer 24(6):2575–2581

    Article  PubMed  Google Scholar 

  40. Zaiem A, Hammamia SB, Aouinti I, Charfi O, Ladhari W, Kastalli S, Aidli SE, Lakhoua G (2022) Hand-foot syndrome induced by chemotherapy drug: case series study and literature review. Indian J Pharmacol 54(3):208–215

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Liu Y, May BH, Zhang AL, Guo X, Lu C, Xue CC, Zhang H (2019) Integrative herbal medicine for chemotherapy-induced peripheral neuropathy and hand-foot syndrome in colorectal cancer: a systematic review and meta-analysis. Integr Cancer Ther 18:1534735418817833

    Article  PubMed  Google Scholar 

  42. Meng W, Zeng X, Gao Y, Chen Q, Bai L (2021) Efficacy of Aidi injection and Brucea javanica oil emulsion injection in rectal cancer during CapeOX adjuvant chemotherapy. Biomed Res Int 2021:2033353

    Article  PubMed  PubMed Central  Google Scholar 

  43. Lan TC, Tsou PH, Tam KW, Huang TW (2022) Effect of urea cream on hand-foot syndrome in patients receiving chemotherapy a meta-analysis. Cancer Nurs 45(5):378–386

    Article  PubMed  Google Scholar 

  44. Iimura Y, Furukawa N, Ishibashi M, Ahiko Y, Tanabe T, Aikou S, Shida D, Nojima M, Kuroda S, Boku N (2022) Study protocol of a single-arm phase 2 study evaluating the preventive effect of topical hydrocortisone for capecitabine-induced hand-foot syndrome in colorectal cancer patients receiving adjuvant chemotherapy with capecitabine plus oxaliplatin (T-CRACC study). BMC Gastroenterol 22(1):341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This research was supported by Medical Scientific Research Foundation of Guangdong Province, China (grant number: A2020374).

Author information

Authors and Affiliations

  1. Operating Room, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

    Jingjuan Huang

  2. Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangzhou Medical University, No 151, Yanjiang Rd, Guangzhou 510120, Guangdong Province, China

    Sihua Ye, Shaolan Feng, Minqi Zheng & Meihua Zhong

Authors
  1. Jingjuan Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sihua Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shaolan Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Minqi Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Meihua Zhong
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Jingjuan Huang and Meihua Zhong. The first draft of the manuscript was written by Jingjuan Huang, and all authors reviewed the content of the manuscript. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Meihua Zhong.

Ethics declarations

Ethical approval

The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's Note

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

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 212 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Huang, J., Ye, S., Feng, S. et al. Prevalence of hand-foot syndrome following chemotherapy for colorectal cancer: a systematic review and meta-analysis. Int J Colorectal Dis 38, 61 (2023). https://doi.org/10.1007/s00384-023-04345-5

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00384-023-04345-5

Keywords

Search

Navigation