Document Type : Original Article

Authors

1 Radiation Oncology Department, Isfahan University of Medical Sciences, Isfahan, Iran

2 Cancer Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

3 Hematology Oncology Department, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Hand-foot syndrome (HFS) is a prevalent skin reaction to cytotoxic systemic therapy, mainly Capecitabine.
The present study aimed to determine etiologies of HFS in addition to its prevention in colorectal cancer patients with Capecitabine-containing chemotherapy regimen.
Method: In this randomized double-blinded study, we recruited 66 eligible patients. The first 33 patients received 25 mg captopril twice daily while the other 33 were given two placebo tablets.
Results: All the patients were assessable for safety and efficacy. Captopril demonstrated a favorable safety profile. The participants in the two groups did not have any significant differences in terms of the median age and the level of hemoglobin (P = 0.45, P = 0.06, respectively). However, the CEA tumor marker was significantly higher in those with HFS (P < 0.05). The incidence of HFS in men and women were 8 (18.6%) and 3 (13%) cases, respectively, and the patients’ sex did not affect the incidence of this syndrome (P = 0.73).
Furthermore, according to the stage of colorectal cancer, the difference between the two groups was significant (P < 0.05). Meanwhile, there were no significant differences concerning the grade of colorectal cancer (P = 0.2).
Conclusion: The results herein revealed that administration of captopril in colorectal cancer patients with Capecitabine-containing chemotherapy regimen reduced the symptoms and incidence of HFS.
On the other hand, CEA tumor marker and the stage of colorectal cancer were in correlation with incidence of HFS.

Keywords

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination, and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi:10.30476/mejc.2022.93268.1680

  1. Kwakman JJM, Elshot YS, Punt CJA, Koopman M. Management of cytotoxic chemotherapy-induced hand-foot syndrome. Oncol Rev. 2020;14(1):442. doi: 10.4081/oncol.2020.442. 
  2. Komatsu H, Yagasaki K, Hirata K, Hamamoto Y. Unmet needs of cancer patients with chemotherapy-related hand-foot syndrome and targeted therapy-related hand-foot skin reaction: A qualitative study. Eur J Oncol Nurs. 2019;38:65-9. doi: 10.1016/j.ejon.2018.12.001.
  3. Nikolaou V, Syrigos K, Saif MW. Incidence and implications of chemotherapy related hand-foot syndrome. Expert Opin Drug Saf. 2016;15(12):1625-33. doi: 10.1080/14740338.2016.1238067. 
  4. Huang XZ, Chen Y, Chen WJ, Zhang X, Wu CC, Wang ZN, et al. Clinical evidence of prevention strategies for capecitabine-induced hand-foot syndrome. Int J Cancer. 2018;142(12):2567-77. doi: 10.1002/ijc.31269.
  5. Yap YS, Kwok LL, Syn N, Chay WY, Chia JWK, Tham CK, et al. Predictors of hand-foot syndrome and pyridoxine for prevention of capecitabine-induced hand-foot syndrome: A randomized clinical trial. JAMA Oncol. 2017;3(11):1538-45. doi: 10.1001/jamaoncol.2017.1269.
  1. Wheeler HE, González-Neira A, Pita G, de la Torre-Montero JC, Alonso R, Lopez-Fernandez LA, et al. Identification of genetic variants associated with capecitabine-induced hand-foot syndrome through integration of patient and cell line genomic analyses. Pharmacogenet Genomics. 2014;24(5):231-7. doi: 10.1097/FPC.0000000000000037.
  2. Lou Y, Wang Q, Zheng J, Hu H, Liu L, Hong D, et al. Possible pathways of capecitabine-induced hand-foot syndrome. Chem Res Toxicol. 2016;29(10):1591-601. doi: 10.1021/acs.chemrestox.6b00215.
  3. Lokich JJ, Moore C. Chemotherapy-associated palmar-plantar erythrodysesthesia syndrome. Ann Intern Med. 1984;101(6):798-9. doi: 10.7326/0003-4819-101-6-798.
  4. Naito M, Yamamoto T, Hara S, Shimamoto C, Miwa Y. Hemoglobin value is the most important factor in the development of hand-foot syndrome under the capecitabine regimen. 2017;62(1):23-9. doi: 10.1159/000445866.
  5. Kanbayashi Y, Hosokawa T, Yasui K, Hongo F, Yamaguchi K, Moriguchi M, et al. Predictive factors for sorafenib-induced hand-foot skin reaction using ordered logistic regression analysis. Am J Health Syst Pharm. 2016;73(1):e18-23. doi: 10.2146/ajhp150129.
  6. Lassere Y, Hoff P. Management of hand-foot syndrome in patients treated with capecitabine (Xeloda). Eur J Oncol Nurs. 2004;8 Suppl 1:S31-40. doi: 10.1016/j.ejon.2004.06.007.
  7. Saif MW. Capecitabine and hand-foot syndrome. Expert Opin Drug Saf. 2011;10(2):159-69. doi: 10.1517/14740338.2011.546342.
  8. Liao X, Huang L, Yu Q, He S, Li Q, Huang C, et al. SNPs in the COX-2/PGES/EP signaling pathway are associated with risk of severe capecitabine-induced hand-foot syndrome. Cancer Chemother Pharmacol. 2020;85(4):785-92. doi: 10.1007/s00280-020-04053-9.
  9. Zhao C, Chen J, Yu B, Wu X, Dai C, Zhou C, et al. Effect of modified taohongsiwu decoction on patients with chemotherapy-induced hand-foot syndrome. J Tradit Chin Med. 2014;34(1):10-4. doi: 10.1016/s0254-6272(14)60047-9.
  10. Hoesly FJ, Baker SG, Gunawardane ND, Cotliar JA. Capecitabine-induced hand-foot syndrome complicated by pseudomonal superinfection resulting in bacterial sepsis and death: case report and review of the literature. Arch Dermatol. 2011;147(12):1418-23. doi: 10.1001/archdermatol.2011.320.
  11. von Gruenigen V, Frasure H, Fusco N, DeBernardo R, Eldermire E, Eaton S, et al. A double-blind, randomized trial of pyridoxine versus placebo for the prevention of pegylated liposomal doxorubicin-related hand-foot syndrome in gynecologic oncology patients. 2010;116(20):4735-43. doi: 10.1002/cncr.25262.
  12. Zhou Y, Peng L, Li Y, Chen L. Prophylactic pyridoxine was not able to reduce the incidence of capecitabine-induced hand-foot syndrome: A meta-analysis. Biomed Rep. 2013 Nov;1(6):873-878. doi: 10.3892/br.2013.161. Epub 2013 Aug 28. PMID: 24649045; PMCID: PMC3916964.
  13. Lal HS. Hand and foot syndrome secondary to capecitabine. Indian J Dermatol Venereol Leprol. 2014;80(5):427-30. doi: 10.4103/0378-6323.140302.
  14. Nagore E, Insa A, Sanmartín O. Antineoplastic therapy-induced palmar plantar erythrodysesthesia ('hand-foot') syndrome. Incidence, recognition and management. Am J Clin Dermatol. 2000;1(4):225-34. doi: 10.2165/00128071-200001040-00004.
  15. Zhang JZ, Xi X, Gao L, Kern TS. Captopril inhibits capillary degeneration in the early stages of diabetic retinopathy. Curr Eye Res. 2007;32(10):883-9. doi: 10.1080/02713680701584123.
  16. Coppola G, Romano G, Corrado E, Grisanti RM, Novo S. Peripheral artery disease: potential role of ACE-inhibitor therapy. Vasc Health Risk Manag. 2008;4(6):1179-87. doi: 10.2147/vhrm.s3096.
  17. Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, et al. ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. 2006;113(11):e463-654. doi: 10.1161/CIRCULATIONAHA.106.174526.
  18. Heart Outcomes Prevention Evaluation Study Investigators, Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000;342(3):145-53. doi: 10.1056/NEJM200001203420301. Erratum in: N Engl J Med. 2000;342(10):748. PMID: 10639539.