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Hand-Foot Syndrome and Progression-Free Survival in Patients Treated with Sunitinib for Metastatic Clear Cell Renal Cell Carcinoma

  • Jakub Kucharz
  • Monika BudnikEmail author
  • Paulina Dumnicka
  • Maciej Pastuszczak
  • Beata Kuśnierz-Cabala
  • Tomasz Demkow
  • Katarzyna Popko
  • Pawel Wiechno
Part of the Advances in Experimental Medicine and Biology book series


Patients with metastatic clear cell renal cell carcinoma (mRCC) typically receive systemic treatment with tyrosine kinase inhibitors (TKI). Side effects include the hand-foot syndrome (HFS), tiredness, nausea, decreased appetite, diarrhea, myelosuppression, and hypertension. This study seeks to define the relationship between the incidence of HFS after the first cycle of treatment with sunitinib as the first-line treatment for mRCC (50 mg/day, 6-week schedule: 4 weeks on and 2 weeks off) and progression-free survival. We found that patients, treated with sunitinib for mRCC, who did not experience HFS had the median progression-free survival of 9.8 months. HFS symptoms appeared in 20% of patients after the first treatment cycle. The appearance of HFS was a predictor of a longer progression-free survival. In fact, progression-free survival was elongated in the HFS group over and beyond the observation period of 60 months, which rendered the median progression-free survival calculation impossible. These findings reaffirm the importance of monitoring skin toxicity during treatment with TKI. We conclude that the appearance of adverse skin symptoms presages better outcomes in patients treated with sunitinib for mRCC.


Hand-foot syndrome Renal cell carcinoma Sunitinib Survival Tyrosine kinase inhibitors 


Conflicts of Interest

JK received a research grant from Novartis Poland and speaker honoraria from Pfizer, Bayer, and IPSEN companies. PW received speaker honoraria from Pfizer, Bayer, Novartis, and IPSEN. The remaining authors declare no conflicts of interest in relation to this article.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Bioethics Committee (permission no. 38/2018) of the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology in Warsaw, Poland.

Informed Consent

Informed consent was obtained from all individual participants included in the study.


  1. Bono P, Rautiola J, Utriainen T, Joensuu H (2011) Hypertension as predictor of sunitinib treatment outcome in metastatic renal cell carcinoma. Acta Oncol 50:569–573Google Scholar
  2. Buda–Nowak A, Kucharz J, Dumnicka P, Kuzniewski M, Herman RM, Zygulska AL, Kusnierz–Cabala B (2017) Sunitinib–induced hypothyroidism predicts progression–free survival in metastatic renal cell carcinoma patients. Med Oncol 34(4):68Google Scholar
  3. Chow LQ, Eckhardt SG (2007) Sunitinib: from rational design to clinical efficacy. J Clin Oncol 25:884–896Google Scholar
  4. Chu D, Lacouture ME, Fillos T, Wu S (2008) Risk of hand–foot skin reaction with sorafenib: a systematic review and meta–analysis. Acta Oncol 47(2):176–186Google Scholar
  5. ECOG (2018) Eastern cooperative oncology group. Performance status. Accessed on 30 Nov 2018
  6. Escudier B, Eisen T, Stadler W, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai A, Rolland F, Demkow T, Hutson T, Gore M, Freeman S, Schwartz B, Shan M, Simantov R, Bukowski R, for the TARGET Study Group (2007) Sorafenib in advanced clear–cell renal–cell carcinoma. N Engl J Med 356(2):125–134Google Scholar
  7. Escudier B, Porta C, Schmidinger M, Rioux–Leclercq N, Bex A, Khoo V, Gruenvald V, Horwich A, ESMO Guidelines Committee (2016) Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow–up. Ann Oncol 27(suppl 5):58–68Google Scholar
  8. Janusch M, Fischer M, Marsch WC, Holzhausen HJ, Kegel T, Helmbold P (2006) The hand–foot syndrome – a frequent secondary manifestation in antineoplastic chemotherapy. Eur J Dermatol 16(5):494–499Google Scholar
  9. Kucharz J, Giza A, Dumnicka P, Kuzniewski M, Kusnierz–Cabala B, Bryniarski P, Herman R, Zygulska AL, Krzemieniecki K (2016) Macrocytosis during sunitinib treatment predicts progression–free survival in patients with metastatic renal cell carcinoma. Med Oncol 33(10):109Google Scholar
  10. Li J, Gu J (2017) Hand–foot skin reaction with vascular endothelial growth factor receptor tyrosine kinase inhibitors in cancer patients: a systematic review and meta–analysis. Crit Rev Oncol Hematol 119:50–58Google Scholar
  11. Lipworth AD, Robert C, Zhu AX (2009) Hand–foot syndrome (hand–foot skin reaction, palmar–plantar erythrodysesthesia): focus on sorafenib and sunitinib. Oncology 77(5):257–271Google Scholar
  12. Lorusso D, Di Stefano A, Carone V, Fagotti A, Pisconti S, Scambia G (2007) Pegylated liposomal doxorubicin–related palmar–plantar erythrodysesthesia (‘hand–foot’ syndrome). Ann Oncol 18(7):1159–1164Google Scholar
  13. Maráz A, Cserháti A, Uhercsák G, Szilágyi É, Varga Z, Révész J, Kószó R, Varga L, Kahán Z (2018) Dose escalation can maximize therapeutic potential of sunitinib in patients with metastatic renal cell carcinoma. BMC Cancer 18(1):296Google Scholar
  14. Michaelson MD, Cohen DP, Li S, Motzer RJ, Escudier B, Barrios CH, Burnett PE, Puzanov I (2011) Handfoot syndrome (HFS) as a potential biomarker of efficacy in patients (pts) with metastatic renal cell carcinoma (mRCC) treated with sunitinib (SU). J Clin Oncol 29(Suppl 7):Abstr 320Google Scholar
  15. Motzer RJ, Mazumdar M, Bacik J, Berg W, Amsterdam A, Ferrara J (1999) Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol 17(8):2530–2540Google Scholar
  16. Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST, Chen I, Bycott PW, Baum CM, Figlin RA (2007) Sunitinib versus interferon alfa in metastatic renal–cell carcinoma. N Engl J Med 356:115–124Google Scholar
  17. Nakano K, Komatsu K, Kubo T, Natsui S, Nukui A, Kurokawa S, Kobayashi M, Morita T (2013) Hand–foot skin reaction is associated with the clinical outcome in patients with metastatic renal cell carcinoma treated with sorafenib. Jpn J Clin Oncol 43(10):1023–1029Google Scholar
  18. Poprach A, Pavlik T, Melichar B, Puzanov I, Dusek L, Bortlicek Z, Vyzula R, Abrahamova J, Buchler T, Czech Renal Cancer Cooperative Group (2012) Skin toxicity and efficacy of sunitinib and sorafenib in metastatic renal cell carcinoma: a national registry–based study. Ann Oncol 23(12):3137–3143Google Scholar
  19. Pożarowska D, Pożarowski P (2016) The era of anti–vascular endothelial growth factor (VEGF) drugs in ophthalmology, VEGF and anti–VEGF therapy. Cent Eur J Immunol 41:311–316Google Scholar
  20. Ravaud A, Schmidinger M (2013) Clinical biomarkers of response in advanced renal cell carcinoma. Ann Oncol 24:2935–2942Google Scholar
  21. Schmidinger M, Vogl UM, Bojic M, Lamm W, Heinzl H, Haitel A, Clodi M, Kramer G, Zielinski CC (2011) Hypothyroidism in patients with renal cell carcinoma: blessing or curse. Cancer 117(3):534–544Google Scholar
  22. Wyganowska–Swiatkowska M, Urbaniak P, Szkaradkiewicz A, Jankun J, Kotwicka M (2016) Effects of chlorhexidine, essential oils and herbal medicines (salvia, chamomile, calendula) on human fibroblast in vitro. Cent Eur J Immunol 41:125–131Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Jakub Kucharz
    • 1
  • Monika Budnik
    • 2
    Email author
  • Paulina Dumnicka
    • 3
  • Maciej Pastuszczak
    • 4
  • Beata Kuśnierz-Cabala
    • 5
  • Tomasz Demkow
    • 1
  • Katarzyna Popko
    • 6
  • Pawel Wiechno
    • 1
  1. 1.Department of Uro-OncologyMaria Sklodowska-Curie Memorial Cancer Center and Institute of OncologyWarsawPoland
  2. 2.First Chair and Department of CardiologyWarsaw Medical UniversityWarsawPoland
  3. 3.Department of Medical DiagnosticsJagiellonian University Medical CollegeCracowPoland
  4. 4.Department of DermatologyJagiellonian University Medical CollegeCracowPoland
  5. 5.Department of Clinical BiochemistryJagiellonian University Medical CollegeCracowPoland
  6. 6.Department of Laboratory Medicine and Clinical Immunology of Developmental AgeWarsaw Medical UniversityWarsawPoland

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