Prevention Strategies For Chemotherapy-induced Hand-foot Syndrome: A Systematic Review And Meta-analysis Of Prospective Randomised Trials

Purpose: Hand-foot syndrome (HSF) is a distinctive adverse event relatively frequent to some chemotherapeutic agents as capecitabine, pegylated liposomal doxorubicin, sorafenib and other tyrosine-kinase inhibitors. Since the prevention of HFS would be crucial to avoid treatment interruptions and delays, many studies have been conducted with this purpose. Methods: The aim of this systematic review and meta-analysis was to analyze the clinical efficacy of prevention strategies for HFS, through a wide search of electronic databases as well as congress abstracts. The endpoints evaluated were the dichotomic data for mild (Grade 1), moderate to severe (Grades 2 to 3) and all-grade HFS. Meta-analysis was calculated through RevMan v5.1 software. Results: Amongst 295 studies identified, only ten met the inclusion criteria. Celecoxib prevented both moderate to severe (odds ratio [OR] 0.39, 95 % confidence interval [CI] 0.20-0.73, P=0.003) and all-grade HFS (OR 0.47, 95 % CI 0.29-0.78, P=0.003), whereas pyridoxine and topical urea/lactic acid formulations failed to prove efficacy. There were no proven benefits in mild HFS. The use of topical antiperspirant has not been shown to improve results, according to a single trial. Conclusions: From all available possibilities for the prevention of HFS, celecoxib appears to be the most promising, with statistically significant results. Larger, multicentric studies are required to reinforce this finding. © 2014 Springer-Verlag.22615851593Almeida Da Cruz, L., Hoff, P.M., Ferrari, C.L., Riechelmann, R.S., Unilateral hand-foot syndrome: Does it take sides? Case report and literature review (2012) Clin Colorectal Cancer, 11, pp. 82-84Hoesly, F.J., Baker, S.G., Gunawardane, N.D., Cotliar, J.A., Capecitabine-induced hand-foot syndrome complicated by pseudomonal superinfection resulting in bacterial sepsis and death: Case report and review of the literature (2011) Arch Dermatol, 147, pp. 1418-1423Belum, V.R., Wu, S., Lacouture, M.E., Risk of hand-foot skin reaction with the novel multikinase inhibitor regorafenib: A meta-analysis (2013) Invest New Drugs, 31, pp. 1078-1086Fischer, A., Wu, S., Ho, A.L., Lacouture, M.E., The risk of hand-foot skin reaction to axitinib, a novel VEGF inhibitor: A systematic review of literature and meta-analysis (2013) Invest New Drugs, 31, pp. 787-797Balagula, Y., Wu, S., Su, X., The risk of hand foot skin reaction to pazopanib, a novel multikinase inhibitor: A systematic review of literature and meta-analysis (2012) Invest New Drugs, 30, pp. 1773-1781Chu, D., Lacouture, M.E., 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 (2009) Clin Genitourin Cancer, 7, pp. 11-19Lin, E., Morris, J.S., Ayers, G.D., Effect of celecoxib on capecitabine-induced hand-foot syndrome and antitumor activity (2002) Oncology, 16, pp. 31-37. , Williston ParkFitzpatrick, J.E., The cutaneous histopathology of chemotherapeutic reactions (1993) J Cutan Pathol, 20, pp. 1-14Jacobi, U., Waibler, E., Schulze, P., Sehouli, J., Oskay-Ozcelik, G., Schmook, T., Sterry, W., Lademann, J., Release of doxorubicin in sweat: First step to induce the palmar-plantar erythrodysesthesia syndrome? [4] (2005) Annals of Oncology, 16 (7), pp. 1210-1211. , DOI 10.1093/annonc/mdi204Sibaud, V., Dalenc, F., Chevreau, C., HFS-14, a specific quality of life scale developed for patients suffering from hand-foot syndrome (2011) Oncologist, 16, pp. 1469-1478Von Moos, R., Thuerlimann, B.J., Aapro, M., Pegylated liposomal doxorubicin-associated hand-foot syndrome: Recommendations of an international panel of experts (2008) Eur J Cancer, 44, pp. 781-790Trotti, A., Colevas, A.D., Setser, A., Rusch, V., Jaques, D., Budach, V., Langer, C., Rubin, P., CTCAE v3.0: Development of a comprehensive grading system for the adverse effects of cancer treatment (2003) Seminars in Radiation Oncology, 13 (3), pp. 176-181. , DOI 10.1016/S1053-4296(03)00031-6Egger, M., Smith, G.D., Schneider, M., Minder, C., Bias in meta-analysis detected by a simple, graphical test (1997) British Medical Journal, 315 (7109), pp. 629-634Sterne, J.A.C., Egger, M., Funnel plots for detecting bias in meta-analysis: Guidelines on choice of axis (2001) Journal of Clinical Epidemiology, 54 (10), pp. 1046-1055. , DOI 10.1016/S0895-4356(01)00377-8, PII S0895435601003778(2011) Review Manager V5.1. In 5.1 Edition, , http://ims.cochrane.org/revmanLiberati, A., Altman, D.G., Tetzlaff, J., The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration (2009) J Clin Epidemiol, 62, pp. e1-e34Braik, T., Yim, B., Evans, A.T., A randomized trial to determine if vitamin B6 can prevent hand and foot syndrome in cancer patients treated with capecitabine chemotherapy (2012) J Clin Oncol, 30 (SUPPL.). , abstr 9085Corrie, P.G., Bulusu, R., Wilson, C.B., A randomised study evaluating the use of pyridoxine to avoid capecitabine dose modifications (2012) Br J Cancer, 107, pp. 585-587Fabi, A., Metro, G., Papaldo, P., Impact of celecoxib on capecitabine tolerability and activity in pretreated metastatic breast cancer: Results of a phase II study with biomarker evaluation (2008) Cancer Chemother Pharmacol, 62, pp. 717-725Kang, Y.K., Lee, S.S., Yoon, D.H., Pyridoxine is not effective to prevent hand-foot syndrome associated with capecitabine therapy: Results of a randomized, double-blind, placebo-controlled study (2010) J Clin Oncol, 28, pp. 3824-3829Kanis, M., Kesterson, J.P., Lele, S., The use of cod liver oil by patients receiving pegylated liposomal doxorubicin is associated with a lack of severe palmar-plantar erythrodysesthesia (2009) Eur J Gynaecol Oncol, 30, pp. 387-388Kluschke, F., Martschick, A., Darvin, M.E., Application of an ointment with high radical protection factor as a prevention strategy against PPE (2012) J Clin Oncol, 30 (SUPPL.). , abstr 5064Kohne, C.-H., De Greve, J., Hartmann, J.T., Lang, I., Vergauwe, P., Becker, K., Braumann, D., Van Cutsem, E., Irinotecan combined with infusional 5-fluorouracil/folinic acid or capecitabine plus celecoxib or placebo in the first-line treatment of patients with metastatic colorectal cancer. EORTC study 40015 (2008) Annals of Oncology, 19 (5), pp. 920-926. , DOI 10.1093/annonc/mdm544Lyass, O., Lotem, M., Edelmann, D., Protective effect of amifostine (AMF) on doxil/caelyx-induced palmar-plantar erythrodysesthesia (PPE) in patients (pts) with advanced cancer (2001) Clin Oncol, 20. , Proc Am Soc, abstr 2148Mangili, G., Petrone, M., Gentile, C., Prevention strategies in palmar-plantar erythrodysesthesia onset: The role of regional cooling (2008) Gynecol Oncol, 108, pp. 332-335Ren, Z., Zhu, K., Kang, H., A randomized controlled phase II study of the prophylactic effect of urea-based creamon the hand-foot skin reaction associated with sorafenib in advanced hepatocellular carcinoma (2012) J Clin Oncol, 30 (SUPPL.). , abstr 4008Ruhstaller, T., Ribi, K., Sun, H., Prevention of palmoplantar erythrodysesthesia (PPE) with an antiperspirant in breast cancer patients treated with pegylated liposomal doxorubicin (PLD), a placebo-controlled, double blinded, phase lll trial (SAKK 92/08) (2012) J Clin Oncol, 30 (SUPPL.). , abstr 9059Von Gruenigen, V., Frasure, H., Fusco, N., 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) Cancer, 116, pp. 4735-4743Wolf, S.L., Qin, R., Menon, S.P., Placebo-controlled trial to determine the effectiveness of a urea/lactic acid-based topical keratolytic agent for prevention of capecitabine-induced hand-foot syndrome: North Central Cancer Treatment Group Study N05C5 (2010) J Clin Oncol, 28, pp. 5182-5187Yoshimoto, N., Yamashita, T., Fujita, T., Impact of prophylactic pyridoxine on occurrence of hand-foot syndrome in patients receiving capecitabine for advanced or metastatic breast cancer (2010) Breast Cancer, 17, pp. 298-302Zhang, R.X., Wu, X.J., Lu, S.X., The effect of COX-2 inhibitor on capecitabine-induced hand-foot syndrome in patients with stage II/III colorectal cancer: A phase II randomized prospective study (2011) J Cancer Res Clin Oncol, 137, pp. 953-957Zhang, R.X., Wu, X.J., Wan, D.S., Celecoxib can prevent capecitabine-related hand-foot syndrome in stage II and III colorectal cancer patients: Result of a single-center, prospective randomized phase III trial (2012) Ann Oncol, 23, pp. 1348-1353Kawaguchi, K., Ishiguro, H., Morita, S., Correlation between docetaxel-induced skin toxicity and the use of steroids and H(2) blockers: A multi-institution survey (2011) Breast Cancer Res Treat, 130, pp. 627-634Nardone, B., Hensley, J.R., Kulik, L., The effect of hand-foot skin reaction associated with the multikinase inhibitors sorafenib and sunitinib on health-related quality of life (2012) J Drugs Dermatol, 11, pp. e61-e65Gressett, S.M., Stanford, B.L., Hardwicke, F., Management of hand-foot syndrome induced by capecitabine (2006) Journal of Oncology Pharmacy Practice, 12 (3), pp. 131-141. , DOI 10.1177/1078155206069242Rose, P.G., Pegylated liposomal doxorubicin: Optimizing the dosing schedule in ovarian cancer (2005) Oncologist, 10, pp. 205-214Adams, R.A., Meade, A.M., Madi, A., Toxicity associated with combination oxaliplatin plus fluoropyrimidine with or without cetuximab in the MRC COIN trial experience (2009) Br J Cancer, 100, pp. 251-258Maughan, T.S., Adams, R.A., Smith, C.G., Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: Results of the randomised phase 3 MRC COIN trial (2011) Lancet, 377, pp. 2103-2114Johnsen, S.P., Larsson, H., Tarone, R.E., McLaughlin, J.K., Norgard, B., Friis, S., Sorensen, H.T., Risk of hospitalization for myocardial infarction among users of rofecoxib, celecoxib, and other NSAIDs: A population-based case-control study (2005) Archives of Internal Medicine, 165 (9), pp. 978-984. , DOI 10.1001/archinte.165.9.978Chen, Y.F., Jobanputra, P., Barton, P., Cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs (etodolac, meloxicam, celecoxib, rofecoxib, etoricoxib, valdecoxib and lumiracoxib) for osteoarthritis and rheumatoid arthritis: A systematic review and economic evaluation (2008) Health Technol Assess, 12, pp. 1-278+iiiFuchs, C.S., Marshall, J., Mitchell, E., Wierzbicki, R., Ganju, V., Jeffery, M., Schulz, J., Barrueco, J., Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: Results from the BICC-C study (2007) Journal of Clinical Oncology, 25 (30), pp. 4779-4786. , http://jco.ascopubs.org/cgi/reprint/25/30/4779, DOI 10.1200/JCO.2007.11.3357Fabian, C.J., Molina, R., Slavik, M., Dahlberg, S., Giri, S., Stephens, R., Pyridoxine therapy for palmar-plantar erythrodysesthesia associated with continuous 5-fluorouracil infusion (1990) Investigational New Drugs, 8 (1), pp. 57-6