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Chemotherapy-induced hand foot syndrome: comparative efficacy and safety of pharmacological prophylaxis – systematic review and Bayesian network meta-analysis
  1. Mathan Kumar Ramasubbu1,
  2. Shampa Maji1,
  3. Milan Padhan1,
  4. Rituparna Maiti1,
  5. Debasish Hota1,
  6. Saroj Kumar Das Majumdar2 and
  7. Anand Srinivasan1
  1. 1Department of Pharmacology, All India Institute of Medical Sciences, Bhubaneswar, Orissa, India
  2. 2Department of Radiation Oncology, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
  1. Correspondence to Dr Anand Srinivasan, Department of Pharmacology, All India Institute of Medical Sciences - Bhubaneswar, Bhubaneswar, Orissa, 751019, India; anandsrinivasan{at}


Background Hand-foot syndrome (HFS) is one of the most common toxicities experienced by patients receiving systemic chemotherapy agents such as capecitabine and multikinase inhibitors such as sorafenib. Several randomised controlled trials (RCTs) have investigated the efficacy and safety of prophylactic agents such as pyridoxine, celecoxib, urea cream and cystine/theanine in managing HFS. This network meta-analysis (NMA) evaluated data from high-quality trials to provide strong evidence in forming recommendations to prevent systemic cancer therapy-induced HFS.

Objective To examine the comparative efficacy and safety of interventions for preventing systemic chemotherapy-induced HFS in patients with cancer.

Methods We searched PubMed, Embase and clinical trial registry for RCTs of interventions for preventing HFS. Bayesian NMA was performed to estimate the OR with 95% credible intervals (CrI) from both direct and indirect evidence. The outcome measures were the incidence of HFS (grade ≥1) and moderate to severe HFS (grade ≥2). Adverse drug reactions were discussed descriptively.

Results A total of 15 RCTs with 2715 patients with 12 prophylactic strategies were included. The analysis showed only celecoxib could significantly prevent the incidence of moderate to severe HFS (grade ≥2) (OR 0.29, 95% CrI 0.13 to 0.68). But none of the preventive interventions could prevent the incidence of HFS (grade ≥1).

Conclusion Only celecoxib (200 mg two times per day) showed significant prevention of the incidence of moderate to severe HFS. Pyridoxine (400 mg once daily) and urea cream (10%) have to be evaluated further in larger randomised trials.

  • Breast
  • Pharmacology
  • Skin care
  • Gastrointestinal (lower)
  • Clinical decisions
  • Supportive care

Data availability statement

No data are available.

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  • Contributors Conceptualisation: MKR and AS. Methodology: AS and RM. Data curation: MKR, MP, SM. Analysis, software, writing-reviewing and editing: AS and MKR. Validation, visualisation, investigation, interpretation: DH and SM. All authors participated in writing the draft of the article or revising it for intellectual content and final approval of the version to be published. All authors reviewed and approved the manuscript before it was submitted for publication. The author who is responsible for the overall conduct of the work (guarantor) is AS.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.