References

Accord-UK Ltd. Capecitabine Actavis 500mg film-coated tablets. 2017. https://www.medicines.org.uk/emc/medicine/28428 (accessed 22 January 2020)

Artac M, Koral L, Toy H, Guler T, Boruban MC, Altundag K. Complete response and long-term remission to anti-HER2 combined therapy in a patient with breast cancer presented with bone marrow metastases. J Oncol Pharm Pract.. 2014; 20:(2)141-145 https://doi.org/10.1177/1078155213480201

Blum JL, Jones SE, Buzdar AU. Multicenter phase II study of capecitabine in paclitaxel-refractory metastatic breast cancer. J Clin Oncol.. 1999; 17:(2)485-493 https://doi.org/10.1200/JCO.1999.17.2.485

Boekhout AH, Beijnen JH, Schellens JHM. Trastuzumab. Oncologist. 2011; 16:(6)800-810 https://doi.org/10.1634/theoncologist.2010-0035

Brufsky A. Trastuzumab-based therapy for patients with HER2-positive breast cancer: from early scientific development to foundation of care. Am J Clin Oncol.. 2010; 33:(2)186-195

Cardoso F, Costa A, Norton L 1st International consensus guidelines for advanced breast cancer (ABC 1). Breast. 2012; 21:(3)242-252 https://doi.org/10.1016/j.breast.2012.03.003

Cervantes G, Torrecillas L, Erazo AA Capecitabine (Xeloda) as treatment after failure to taxanes for metastatic breast cancer. Proceedings of the American Society of Clinical Oncology. 2000; 19

Dranitsaris G, Beegle N, Kalberer T, Blau S, Cox D, Faria C. A comparison of toxicity and health care resource use between eribulin, capecitabine, gemcitabine, and vinorelbine in patients with metastatic breast cancer treated in a community oncology setting. J Oncol Pharm Pract.. 2015; 21:(3)170-177 https://doi.org/10.1177/1078155214525369

Ewer MS, Gibbs HR, Swafford J, Benjamin RS. Cardiotoxicity in patients receiving trastuzumab (Herceptin): primary toxicity, synergistic or sequential stress, or surveillance artifact?. Semin Oncol.. 1999; 26:(4)96-101

Gefen A, Dilmoney B. Mechanics of the normal woman's breast. Technol Health Care. 2007; 15:(4)259-271 https://doi.org/10.3233/THC-2007-15404

Hassiotou F, Geddes D. Anatomy of the human mammary gland: current status of knowledge. Clin Anat.. 2013; 26:(1)29-48 https://doi.org/10.1002/ca.22165

Hayes DF, Thor AD. c-erbB-2 in breast cancer: development of a clinically useful marker. Semin Oncol.. 2002; 29:(3)231-245 https://doi.org/10.1053/sonc.2002.32899

Hofheinz R-D, Heinemann V, von Weikersthal LF Capecitabine-associated hand–foot–skin reaction is an independent clinical predictor of improved survival in patients with colorectal cancer. Br J Cancer. 2012; 107:(10)1678-1683 https://doi.org/10.1038/bjc.2012.434

Iannello A, Ahmad A. Role of antibody-dependent cell-mediated cytotoxicity in the efficacy of therapeutic anti-cancer monoclonal antibodies. Cancer Metastasis Rev.. 2005; 24:(4)487-499 https://doi.org/10.1007/s10555-005-6192-2

Ishida T, Kiba T, Takeda M Phase II study of capecitabine and trastuzumab combination chemotherapy in patients with HER2 overexpressing metastatic breast cancers resistant to both anthracyclines and taxanes. Cancer Chemother Pharmacol.. 2009; 64:(2)361-369 https://doi.org/10.1007/s00280-008-0882-8

Jackisch C, Hegg R, Stroyakovskiy D HannaH phase III randomised study: association of total pathological complete response with event-free survival in HER2-positive early breast cancer treated with neoadjuvant–adjuvant trastuzumab after 2 years of treatment-free follow-up. Eur J Cancer. 2016; 62:62-75 https://doi.org/10.1016/j.ejca.2016.03.087

HER2-directed therapy for metastatic breast cancer. 2013. https://tinyurl.com/qqqo84s

Jesinger RA. Breast anatomy for the interventionalist. Tech Vasc Interv Radiol.. 2014; 17:(1)3-9 https://doi.org/10.1053/j.tvir.2013.12.002

Joint Formulary Committee. British National Formulary online. 2020. https://bnf.nice.org.uk (accessed 27 January 2020)

Kang YK, Lee SS, Yoon DH Pyridoxine is not effective to prevent hand-foot syndrome associated with capecitabine therapy: results of a randomized, double-blind, placebo-controlled study. J Clin Oncol.. 2010; 28:(24)3824-3829 https://doi.org/10.1200/JCO.2010.29.1807

Kuilenburg ABP, Meijer J, Tanck MWT Phenotypic and clinical implications of variants in the dihydropyrimidine dehydrogenase gene. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 2016; 1862:(4)754-762 https://doi.org/10.1016/j.bbadis.2016.01.009

Lam SW, Guchelaar HJ, Boven E. The role of pharmacogenetics in capecitabine efficacy and toxicity. Cancer Treat Rev.. 2016; 50:9-22 https://doi.org/10.1016/j.ctrv.2016.08.001

Law A, Dyson S, Anthony D. An exploratory study to identify risk factors for the development of capecitabine-induced Palmar Plantar Erythrodysesthesia (PPE). J Adv Nurs.. 2015; 71:(8)1825-1832 https://doi.org/10.1111/jan.12639

Li CI, Moe RE, Daling JR. Risk of mortality by histologic type of breast cancer among women aged 50 to 79 years. Arch Intern Med.. 2003; 163:(18)2149-2153 https://doi.org/10.1001/archinte.163.18.2149

Lobo ED, Hansen RJ, Balthasar JP. Antibody pharmacokinetics and pharmacodynamics. J Pharm Sci.. 2004; 93:(11)2645-2668 https://doi.org/10.1002/jps.20178

Martín M, Martínez N, Ramos M Standard versus continuous administration of capecitabine in metastatic breast cancer (GEICAM/2009-05): a randomized, noninferiority phase II trial with a pharmacogenetic analysis. Oncologist. 2015; 20:(2)111-112 https://doi.org/10.1634/theoncologist.2014-0379

Michaud LB, Jones KL. Recent advances in the systemic management of metastatic breast cancer. Journal of Pharmacy Practice. 2002; 15:(1)52-61 https://doi.org/10.1106/WFQY-VTFL-WLMC-TPE0

Montemurro F. Should trastuzumab be administered concomitantly with anthracycline in women with early, HER2-positive breast cancer?. Transl Cancer Res.. 2014; 3:(6)541-546

National Cancer Institute. Metastatic cancer. 2017. http://www.cancer.gov/types/metastatic-cancer (accessed 22 January 2020)

Polk A, Vaage-Nilsen M, Vistisen K, Nielsen DL. Cardiotoxicity in cancer patients treated with 5-fluorouracil or capecitabine: A systematic review of incidence, manifestations and predisposing factors. Cancer Treat Rev.. 2013; 39:(8)974-984 https://doi.org/10.1016/j.ctrv.2013.03.005

Rajora A, Chow KS, Vu TT, Chambers CR. Documentation of capecitabine usage as a third-line chemotherapy option for metastatic breast cancer patients. J Oncol Pharm Pract.. 2001; 6:(4)139-145 https://doi.org/10.1177/107815520100600402

Richards D, Coleman J, Reynolds J, Aronson J. Oxford handbook of practical drug therapy, 2nd edn. Oxford: Oxford University Press; 2011

Roche. Roche's Herceptin given by subcutaneous injection offers greater convenience to patients and reduces overall healthcare costs compared to standard IV infusion Investor update. 2012. https://tinyurl.com/w9tz2xk (accessed 22 January 2020)

Roche Products Ltd. Xeloda (capecitabine) 150mg film-coated tablets/500mg film-coated tablets. Patient information leaflet. 2019a. https://www.medicines.org.uk/emc/product/1319/pil (accessed 22 January 2020)

Roche Products Ltd. Herceptin 600mg solution for injection in vial. Summary of product characteristics. 2019b. https://www.medicines.org.uk/emc/medicine/28179 (accessed 22 January 2020)

Sadler TW. Langman's medical embryology, 11th edn. Baltimore (MD): Lippincott Williams and Wilkins; 2009

Schaller G, Fuchs I, Gonsch T Phase II study of capecitabine plus trastuzumab in human epidermal growth factor receptor 2 overexpressing metastatic breast cancer pretreated with anthracyclines or taxanes. J Clin Oncol.. 2007; 25:(22)3246-3250 https://doi.org/10.1200/JCO.2006.09.6826

Schellens JHM. Capecitabine. Oncologist. 2007; 12:(2)152-155 https://doi.org/10.1634/theoncologist.12-2-152

Shah NR, Shah A, Rather A. Ventricular fibrillation as a likely consequence of capecitabine-induced coronary vasospasm. J Oncol Pharm Pract.. 2012; 18:(1)132-135 https://doi.org/10.1177/1078155211399164

Singh BN, Malhotra BK. Effects of food on the clinical pharmacokinetics of anticancer agents: underlying mechanisms and implications for oral chemotherapy. Clin Pharmacokinet. 2004; 43:(15)1127-1156 https://doi.org/10.2165/00003088-200443150-00005

Slamon D, Clark G, Wong S, Levin W, Ullrich A, McGuire W. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987; 235:(4785)177-182 https://doi.org/10.1126/science.3798106

Sliwkowski MX, Lofgren JA, Lewis GD, Hotaling TE, Fendly BM, Fox JA. Nonclinical studies addressing the mechanism of action of trastuzumab (Herceptin). Semin Oncol.. 1999; 26:(4)60-70

Summerhayes M. Capecitabine: a novel, orally administered, tumour-activated treatment for breast cancer. J Oncol Pharm Pract.. 2002; 8:(1)1-17 https://doi.org/10.1191/1078155202jp086oa

Tezer M, Bakkaloğlu H, Ergüven M, Bilir A, Kadioğlu A. Smooth muscle morphology in the nipple-areola complex. J Morphol Sci.. 2011; 28:(3)171-175

Tsutsui S, Ohno S, Murakami S, Hachitanda Y, Oda S. Prognostic value of c-erbB2 expression in breast cancer. J Surg Oncol.. 2002; 79:(4)216-223 https://doi.org/10.1002/jso.10079

Twelves C, Scheithauer W, McKendrick J. Capecitabine versus 5-fluorouracil/folinic acid as adjuvant therapy for stage III colon cancer: final results from the X-ACT trial with analysis by age and preliminary evidence of a pharmacodynamic marker of efficacy. Ann Oncol.. 2012; 23:(5)1190-1197 https://doi.org/10.1093/annonc/mdr366

Tyler T. Drug interactions in metastatic breast cancer. J Oncol Pharm Pract.. 2011; 17:(3)236-245 https://doi.org/10.1177/1078155210379167

Visvader JE. Keeping abreast of the mammary epithelial hierarchy and breast tumorigenesis. Genes Dev.. 2009; 23:(22)2563-2577 https://doi.org/10.1101/gad.1849509

Wang J, Iyer S, Fielder PJ, Davis JD, Deng R. Projecting human pharmacokinetics of monoclonal antibodies from nonclinical data: comparative evaluation of prediction approaches in early drug development. Biopharm Drug Dispos.. 2016; 37:(2)51-65 https://doi.org/10.1002/bdd.1952

Watanabe T, Katsumata N, Sasaki Y A multicentre phase II trial of Xeloda (capecitabine) in patients with docetaxel-refractory advanced/metastatic breast cancer. Proceedings of the American Society of Clinical Oncology. 2001; 20

Weigelt B, Peterse JL, van't Veer LJ. Breast cancer metastasis: markers and models. Nat Rev Cancer. 2005; 5:(8)591-602 https://doi.org/10.1038/nrc1670

Wolf SL, Qin R, Menon SP 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. J Clin Oncol.. 2010; 28:(35)5182-5187 https://doi.org/10.1200/JCO.2010.31.1431

Pharmacotherapeutics of capecitabine and trastuzumab in the treatment of metastatic breast cancer

13 February 2020
Breast Cancer
02 February 2020
Volume 29 · Issue 3

Abstract

Metastatic HER2-positive breast cancer is an incurable disease with a poor prognosis. This article presents a critical appraisal of two treatments commonly used in the treatment of metastatic HER2-positive breast cancer: the oral chemotherapy drug, capecitabine, and the monoclonal antibody, trastuzumab. What follows is a critical discussion of the pharmacotherapeutics of capecitabine and trastuzumab, which considers their use both as single agents and as a combination regimen in the treatment of metastatic breast cancer. The implications of side effects of these drugs are discussed, both individually and in combination, as are the challenges these bring to the prescriber. The article evaluates the use of these agents and concludes that the combination of capecitabine and trastuzumab is an attractive treatment option for patients and for the prescriber.

The human breast develops as a result of genetic and hormonal stimulus from skin precursor cells, known as ectoderm, occurring during the fourth week of embryonic development (Sadler, 2009). Unlike most other organs, which develop to maturity at the embryonic stage, the female breast only reaches a matured functioning state in adulthood during the pregnancy-lactation cycle (Hassiotou and Geddes, 2013). It is comprised of adipose and glandular tissue supported by connective tissue called ‘Cooper's ligaments’ (Gefen and Dilmoney, 2007). The glandular tissue drains via the ductal system (Hassiotou and Geddes, 2013) where each duct wall consists of two layers of epithelial cells all fixed within a fibrous stroma (Visvader, 2009). The innermost layer contains cuboidal epithelial cells, some of which can transform into milk-secretory cells during lactation. It is these epithelial cells where the majority of breast malignancies begin (Li et al, 2003). The exterior layer consists of contractile myoepithelial cells, which encapsulate the inner layer and have attributes of smooth muscle cells (Tezer et al, 2011).

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Breast cancer
HER2
Capecitabine
Trastuzumab
Prescribing
Systemic anti-cancer therapy (SACT)