Regorafenib-associated hand-foot skin reaction: Practical advice on diagnosis, prevention, and management

Annals of Oncology

Volumn 26, Issue 10, 2015, Pages 2017-2026

  McLellan, Beth ^a   Ciardiello, F ^b   Lacouture, M E ^c   Segaert, S ^d   Van Cutsem, E ^d  

^a ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

^b SECOND UNIVERSITY OF NAPLES   (Italy)

^c MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^d UNIVERSITY HOSPITALS LEUVEN   (Belgium)

Author keywords

Hand foot skin reaction; Hand foot syndrome; Palmar plantar erythrodysesthesia; Regorafenib; Symptom management; Treatment modifications

Indexed keywords

ALPHA TOCOPHEROL; ANTHRACYCLINE DERIVATIVE; AXITINIB; CABOZANTINIB; CAPECITABINE; CERAMIDE; CETIRIZINE; CHINESE DRUG; CLOBETASOL; CORTICOSTEROID; CYTOTOXIC AGENT; DABRAFENIB; FLUOROPYRIMIDINE DERIVATIVE; FLUOROURACIL; GEFITINIB; HEPARIN; IMATINIB; KERATOLYTIC AGENT; PAZOPANIB; PHOSPHOTRANSFERASE INHIBITOR; PSORALEN; PYRIDOXINE; REGORAFENIB; SORAFENIB; SUNITINIB; TAOHONGSIWU; TAXANE DERIVATIVE; UNCLASSIFIED DRUG; UREA; VEMURAFENIB; CARBANILAMIDE DERIVATIVE; PROTEIN KINASE INHIBITOR; PYRIDINE DERIVATIVE;

BLISTER; COLORECTAL CANCER; DERMATOLOGIST; DYSESTHESIA; ERYTHEMA; HAND FOOT SYNDROME; HUMAN; HYPERKERATOSIS; MEDICAL EXPERT; ONCOLOGIST; PAIN; PATIENT EDUCATION; PHOTOTHERAPY; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SKIN EXAMINATION; SKIN TOXICITY; SYSTEMATIC REVIEW (TOPIC); TREATMENT RESPONSE; ULTRAVIOLET A RADIATION; ULTRAVIOLET B RADIATION; CLINICAL TRIAL (TOPIC); DISEASE MANAGEMENT; GASTROINTESTINAL NEOPLASMS; HAND-FOOT SYNDROME; PROGNOSIS; RISK FACTOR;

CLINICAL TRIALS AS TOPIC; DISEASE MANAGEMENT; GASTROINTESTINAL NEOPLASMS; HAND-FOOT SYNDROME; HUMANS; PHENYLUREA COMPOUNDS; PROGNOSIS; PROTEIN KINASE INHIBITORS; PYRIDINES; RISK FACTORS;

EID: 84943779809     PISSN: 09237534     EISSN: 15698041     Source Type: Journal    
DOI: 10.1093/annonc/mdv244     Document Type: Review

References (84)

1. Wilhelm SM, Dumas J, Adnane L et al. Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int J Cancer 2011; 129:245-255.
2. Schmieder R, Hoffmann J, Becker M et al. Regorafenib (BAY 73-4506): antitumor and antimetastatic activities in preclinical models of colorectal cancer. Int J Cancer 2014; 135: 1487-1496.
3. Mross K, Frost A, Steinbild S et al. A phase I dose-escalation study of regorafenib (BAY 73-4506), an inhibitor of oncogenic, angiogenic, and stromal kinases, in patients with advanced solid tumors. Clin Cancer Res 2012; 18: 2658-2667.
4. Strumberg D, Scheulen ME, Schultheis B et al. Regorafenib (BAY 73-4506) in advanced colorectal cancer: a phase I study. Br J Cancer 2012; 106:1722-1727.
5. Sunakawa Y, Furuse J, Okusaka T et al. Regorafenib in Japanese patients with solid tumors: phase I study of safety, efficacy, and pharmacokinetics. Invest New Drugs 2014; 32: 104-112.
6. Eisen T, Joensuu H, Nathan PD et al. Regorafenib for patients with previously untreated metastatic or unresectable renal-cell carcinoma: a single-group phase 2 trial. Lancet Oncol 2012; 13: 1055-1062.
7. Bruix J, Tak WY, Gasbarrini A et al. Regorafenib as second-line therapy for intermediate or advanced hepatocellular carcinoma: multicentre, open-label, phase II safety study. Eur J Cancer 2013; 49: 3412-3419.
8. George S, Wang Q, Heinrich MC et al. Efficacy and safety of regorafenib in patients with metastatic and/or unresectable GI stromal tumor after failure of imatinib and sunitinib: a multicenter phase II trial. J Clin Oncol 2012; 30: 2401-2407.
9. Demetri GD, Reichardt P, Kang YK et al. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013; 381: 295-302.
10. Grothey A, Van Cutsem E, Sobrero A et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013; 381: 303-312.
11. Li J, Qin S, Xu R et al. Regorafenib monotherapy in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2015; 16: 619-629.
12. Belum VR, Wu S, Lacouture ME. Risk of hand-foot skin reaction with the novel multikinase inhibitor regorafenib: a meta-analysis. Invest New Drugs 2013; 31:1078-1086.
13. Chu D, Lacouture ME, Fillos T, Wu S. Risk of hand-foot skin reaction with sorafenib:a systematic review and meta-analysis. Acta Oncol 2008; 47: 176-186.
14. Chu D, Lacouture ME, Weiner E, Wu S. Risk of hand-foot skin reaction with the multitargeted kinase inhibitor sunitinib in patients with renal cell and non-renal cell carcinoma: a meta-analysis. Clin Genitourin Cancer 2009; 7: 11-19.
15. Jain L, Sissung TM, Danesi R et al. Hypertension and hand-foot skin reactions related to VEGFR2 genotype and improved clinical outcome following bevacizumab and sorafenib. J Exp Clin Cancer Res 2010;29: 95.
16. Otsuka T, Eguchi Y, Kawazoe S et al. Skin toxicities and survival in advanced hepatocellular carcinoma patients treated with sorafenib. Hepatol Res 2012; 42:879-886.
17. Poprach A, Pavlik T, Melichar B et al. Skin toxicity and efficacy of sunitinib and sorafenib in metastatic renal cell carcinoma: a national registry-based study. Ann Oncol 2012; 23: 3137-3143.
18. Nakano K, Komatsu K, Kubo T et al. Hand-foot skin reaction is associated with the clinical outcome in patients with metastatic renal cell carcinoma treated with sorafenib. Jpn J Clin Oncol 2013; 43: 1023-1029.
19. Azad NS, Aragon-Ching JB, Dahut WL et al. Hand-foot skin reaction increases with cumulative sorafenib dose and with combination anti-vascular endothelial growth factor therapy. Clin Cancer Res 2009; 15: 1411-1416.
20. Grothey A, George S, Van Cutsem E et al. Optimizing treatment outcomes with regorafenib: personalized dosing and other strategies to support patient care. Oncologist 2014; 19: 669-680.
21. Mitchell J, Khoukaz T, McNeal D, Brent L. Adverse event management strategies:optimizing treatment with regorafenib in patients with metastatic colorectal cancer. Clin J Oncol Nurs 2014;18: E19-E25.
22. Khan G, Moss RA, Braiteh F, Saltzman M. Proactive strategies for regorafenib in metastatic colorectal cancer: implications for optimal patient management. Cancer Manag Res 2014; 6: 93-103.
23. De Wit M, Boers-Doets CB, Saettini A et al. Prevention and management of adverse events related to regorafenib. Support Care Cancer 2014; 22: 837-846.
24. Chan SL, Ma BB. An update on the safety and efficacy of regorafenib in the treatment of solid cancers. Expert Opin Drug Metab Toxicol 2014; 10: 1607-1614.
25. Sastre J, Argiles G, Benavides M et al. Clinical management of regorafenib in the treatment of patients with advanced colorectal cancer. Clin Transl Oncol 2014; 16: 942-953.
26. Urban C, Anadkat MJ. A review of cutaneous toxicities from targeted therapies in the treatment of colorectal cancers. J Gastrointest Oncol 2013; 4: 319-327.
27. Belum VR, Cercek A, Sanz-Motilva V, Lacouture ME. Dermatologic adverse events to targeted therapies in lower GI cancers: clinical presentation and management. Curr Treat Options Oncol 2013; 14: 389-404.
28. Miller KK, Gorcey L, McLellan BN. Chemotherapy-induced hand-foot syndrome and nail changes: a review of clinical presentation, etiology, pathogenesis, and management. J Am Acad Dermatol 2014; 71: 787-794.
29. Macedo LT, Lima JP, dos Santos LV, Sasse AD. Prevention strategies for chemotherapy-induced hand-foot syndrome: a systematic review and meta-analysis of prospective randomised trials. Support Care Cancer 2014; 22: 1585-1593.
30. Burbach GJ, Zuberbier T. Hand-foot syndrome with tyrosine kinase inhibitor therapy: treatment recommendations [article in German]. Urologe A 2013; 52:1574-1578.
31. Gomez P, Lacouture ME. Clinical presentation and management of hand-foot skin reaction associated with sorafenib in combination with cytotoxic chemotherapy:experience in breast cancer. Oncologist 2011; 16: 1508-1519.
32. Manchen E, Robert C, Porta C. Management of tyrosine kinase inhibitor-induced hand-foot skin reaction: viewpoints from the medical oncologist, dermatologist, and oncology nurse. J Support Oncol 2011; 9: 13-23.
33. Bednarikova D, Kocak I. Hand-foot syndrome after administration of tyrosinkinase inhibitors [article in Czech]. Klin Onkol 2010; 23: 300-305.
34. Degen A, Alter M, Schenck F et al. The hand-foot-syndrome associated with medical tumor therapy-classification and management. J Dtsch Dermatol Ges 2010; 8: 652-661.
35. Yang CH, Chuang CK, Hsieh JJ, Chang JW. Targeted therapy and hand-foot skin reaction in advanced renal cell carcinoma. Expert Opin Drug Saf 2010; 9: 459-470.
36. Lipworth AD, Robert C, Zhu AX. Hand-foot syndrome (hand-foot skin reaction, palmar-plantar erythrodysesthesia): focus on sorafenib and sunitinib. Oncology 2009; 77: 257-271.
37. Anderson R, Jatoi A, Robert C et al. Search for evidence-based approaches for the prevention and palliation of hand-foot skin reaction (HFSR) caused by the multikinase inhibitors (MKIs). Oncologist 2009; 14: 291-302.
38. Milano G, Mortier L, Digue L et al. Hand-foot syndrome and sorafenib [Article in French]. Bull Cancer 2009; 96: 191-197.
39. Lacouture ME, Wu S, Robert C et al. Evolving strategies for the management of hand-foot skin reaction associated with the multitargeted kinase inhibitors sorafenib and sunitinib. Oncologist 2008; 13: 1001-1011.
40. Ren ZG, Zhu KS, Yang HY et al. Randomized controlled trial of the prophylactic effect of urea-based cream on sorafenib-associated hand-foot skin reactions in patients with advanced hepatocellular carcinoma. J Clin Oncol 2015; 33:894-900.
41. Shinohara N, Nonomura N, Eto M et al. A randomized multicenter phase II trial on the efficacy of a hydrocolloid dressing containing ceramide with a low-friction external surface for hand-foot skin reaction caused by sorafenib in patients with renal cell carcinoma. Ann Oncol 2014; 25: 472-476.
42. Li JR, Yang CR, Cheng CL et al. Efficacy of a protocol including heparin ointment for treatment of multikinase inhibitor-induced hand-foot skin reactions. Support Care Cancer 2013; 21: 907-911.
43. Bozkurt DB, Kara B, Oguz KI et al. Hand-foot syndrome due to sorafenib in hepatocellular carcinoma treated with vitamin E without dose modification; a preliminary clinical study. J BUON 2011; 16: 759-764.
44. Zhao C, Chen J, Yu B et al. Effect of modified taohongsiwu decoction on patients with chemotherapy-induced hand-foot syndrome. J Tradit Chin Med 2014; 34:10-14.
45. Sil A, Das NK. Sorafenib-induced hand-foot syndrome in a patient of renal cell carcinoma. Indian J Pharmacol 2014; 46: 334-336.
46. Vanneste L, Wolter P, Van den Oord JJ et al. Cutaneous adverse effects of BRAF inhibitors in metastatic malignant melanoma, a prospective study in 20 patients. J Eur Acad Dermatol Venereol 2014; 29: 61-68.
47. Hung CT, Chiang CP, Wu BY. Sorafenib-induced psoriasis and hand-foot skin reaction responded dramatically to systemic narrowband ultraviolet B phototherapy. J Dermatol 2012; 39: 1076-1077.
48. Bos WE, Nijsten TE, de Jonge MJ, Hamberg AP. Topical psoralen plus UV-A therapy for tyrosine kinase inhibitor-induced hand-foot syndrome. Arch Dermatol 2012; 148: 546-547.
49. Sibaud V, Delord JP, Chevreau C. Sorafenib-induced hand-foot skin reaction: a Koebner phenomenon?. Target Oncol 2009; 4: 307-310.
50. Echeverria B, Llombart B, Botella-Estrada R, Guillen C. Palmoplantar cutaneous reaction to sorafenib [article in Spanish]. Actas Dermosifiliogr 2009; 100: 736-737.
51. Hutten M, Lassay L, Sachs B et al. Successful topical treatment of sorafenibinduced hand-foot skin reaction in a child with hepatocellular carcinoma. Pediatr Dermatol 2009; 26: 349-350.
52. Lilly E, Burke M, Kluger H, Choi J. Pregabalin for the treatment of painful hand-foot skin reaction associated with dabrafenib. JAMA Dermatol 2014; 151: 102-103.
53. Zuehlke RL. Erythematous eruption of the palms and soles associated with mitotane therapy. Dermatologica 1974; 148: 90-92.
54. Boussemart L, Routier E, Mateus C et al. Prospective study of cutaneous sideeffects associated with the BRAF inhibitor vemurafenib: a study of 42 patients. Ann Oncol 2013; 24: 1691-1697.
55. Hoesly FJ, Baker SG, Gunawardane ND, Cotliar JA. Capecitabine-induced handfoot syndrome complicated by pseudomonal superinfection resulting in bacterial sepsis and death: case report and review of the literature. Arch Dermatol 2011; 147: 1418-1423.
56. Lai SE, Kuzel T, Lacouture ME. Hand-foot and stump syndrome to sorafenib. J Clin Oncol 2007; 25: 341-343.
57. Boone SL, Jameson G, Von Hoff D, Lacouture ME. Blackberry-induced hand-foot skin reaction to sunitinib. Invest New Drugs 2009; 27: 389-390.
58. Robert C, Mateus C, Spatz A et al. Dermatologic symptoms associated with the multikinase inhibitor sorafenib. J Am Acad Dermatol 2009; 60: 299-305.
59. Jacobi U, Waibler E, Schulze P et al. Release of doxorubicin in sweat: first step to induce the palmar-plantar erythrodysesthesia syndrome?. Ann Oncol 2005; 16:1210-1211.
60. Martschick A, Sehouli J, Patzelt A et al. The pathogenetic mechanism of anthracycline-induced palmar-plantar erythrodysesthesia. Anticancer Res 2009; 29: 2307-2313.
61. Templeton AJ, Ribi K, Surber C et al. Prevention of palmar-plantar erythrodysesthesia with an antiperspirant in breast cancer patients treated with pegylated liposomal doxorubicin (SAKK 92/08). Breast 2014; 23: 244-249.
62. Jain L, Gardner ER, Figg WD et al. Lack of association between excretion of sorafenib in sweat and hand-foot skin reaction. Pharmacotherapy 2010; 30:52-56.
63. Lankheet NA, Huitema AD, Mallo H et al. The effect of seasonal variation and secretion of sunitinib in sweat on the development of hand-foot syndrome. Eur J Clin Pharmacol 2013; 69: 2065-2072.
64. Lankheet NA, Blank CU, Mallo H et al. Determination of sunitinib and its active metabolite N-desethylsunitinib in sweat of a patient. J Anal Toxicol 2011; 35:558-565.
65. Lacouture ME, Reilly LM, Gerami P, Guitart J. Hand foot skin reaction in cancer patients treated with the multikinase inhibitors sorafenib and sunitinib. Ann Oncol 2008; 19: 1955-1961.
66. Lee WJ, Lee JL, Chang SE et al. Cutaneous adverse effects in patients treated with the multitargeted kinase inhibitors sorafenib and sunitinib. Br J Dermatol 2009; 161: 1045-1051.
67. Grothey A, Sobrero AF, Siena S et al. Time profile of adverse events (AEs) from regorafenib (REG) treatment for metastatic colorectal cancer (mCRC) in the phase III CORRECT study. J Clin Oncol 2013; 31(Suppl): abstr 3637.
68. Gomez-Martin C, Sanchez A, Irigoyen A et al. 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. Clin Transl Oncol 2012; 14:689-697.
69. Gressett SM, Stanford BL, Hardwicke F. Management of hand-foot syndrome induced by capecitabine. J Oncol Pharm Pract 2006; 12: 131-141.
70. Rosen AC, Case EC, Dusza SW et al. Impact of dermatologic adverse events on quality of life in 283 cancer patients: a questionnaire study in a dermatology referral clinic. Am J Clin Dermatol 2013; 14: 327-333.
71. McLellan B, Kerr H. Cutaneous toxicities of the multikinase inhibitors sorafenib and sunitinib. Dermatol Ther 2011; 24: 396-400.
72. Charles C, Sultan S, Bungener C et al. Impact of cutaneous toxicities associated with targeted therapies on quality of life. Results of a longitudinal exploratory study [article in French]. Bull Cancer 2013; 100: 213-222.
73. Nardone B, Hensley JR, Kulik L et al. The effect of hand-foot skin reaction associated with the multikinase inhibitors sorafenib and sunitinib on health-related quality of life. J Drugs Dermatol 2012;11: e61-e65.
74. Haley AC, Calahan C, Gandhi M et al. Skin care management in cancer patients:an evaluation of quality of life and tolerability. Support Care Cancer 2011; 19:545-554.
75. Dreno B, Bensadoun RJ, Humbert P et al. Algorithm for dermocosmetic use in the management of cutaneous side-effects associated with targeted therapy in oncology. J Eur Acad Dermatol Venereol 2013; 27: 1071-1080.
76. Borovicka JH, Calahan C, Gandhi M et al. Economic burden of dermatologic adverse events induced by molecularly targeted cancer agents. Arch Dermatol 2011; 147: 1403-1409.
77. Dranitsaris G, Vincent MD, Yu J et al. Development and validation of a prediction index for hand-foot skin reaction in cancer patients receiving sorafenib. Ann Oncol 2012; 23: 2103-2108.
78. Tsuchiya N, Narita S, Inoue T et al. Risk factors for sorafenib-induced high-grade skin rash in Japanese patients with advanced renal cell carcinoma. Anticancer Drugs 2013; 24: 310-314.
79. Chren MM, Lasek RJ, Sahay AP, Sands LP. Measurement properties of Skindex-16: a brief quality-of-life measure for patients with skin diseases. J Cutan Med Surg 2001; 5: 105-110.
80. Lewis V, Finlay AY. 10 years experience of the Dermatology Life Quality Index (DLQI). J Investig Dermatol Symp Proc 2004; 9: 169-180.
81. Sibaud V, Dalenc F, Chevreau C et al. HFS-14, a specific quality of life scale developed for patients suffering from hand-foot syndrome. Oncologist 2011; 16:1469-1478.
82. DeSimone PA. Nightly dosing of regorafenib. J Clin Oncol 2015; 33(Suppl): abstr 549.
83. Tabchi S, Ghosn M. Regorafenib: start low and go slow. Target Oncol 2015; 10(3):445-447.
84. National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. http://evs.nci.nih.gov/ftp1/CTCAE/About.html (20 April 2015, date last accessed).