FEC 75 and Nausea and vomiting

In this essay I will talk about a type of systemic anti cancer treatment, FEC 75. This regimen is a combination of: Fluorouracil, Epirubicin and Cyclophosphamide. Combination regimens are more effective than single agent regimens (Rang et al., 2012). According to Lehne (2013, p. 1264) the aims of combination chemotherapy are to prevent drug resistance, increase cancer cell kill and reduce general toxicity.

Authors:

David Casalduero Cidón

Asunción Cuenca Sanchez

María Dolores Cuenca Sanchez

Breast cancer is the most common of all malignant diseases in women with an annual incidence of almost 44,000 new cases in the UK (Grimsey, 2011, p. 1). This combination therapy is highly effective to treat patients with a diagnosis of breast cancer. FEC 75 is frequently used post surgery or radiotherapy and this is known as adjuvant therapy (Eadens and Ajithkumar, 2011 p.162). According to Johnston (2005,

p. 276) ‘the aim of systemic adjuvant therapy is to reduce the risk of breast cancer recurrence’. The table below (Table 1) illustrates chemotherapy drugs used in breast cancer systemic treatment.

Normal cell cycle consists of five major phases: G0, G1, S, G2 and M phase. The continued loss of cell cycle control and accumulation of mutations leads to uncontrolled cell growth or tumor development (Almeida and Barry, 2010). Figure 1 illustrates the stages within a normal cell cycle and mechanism of action of major chemotherapy drugs. Chemotherapy drugs can be classified by mechanism of action (e.g. alkylating agents, antimetabolites, antitumor antibiotics) and propensity to be cell cycle or phase specific (Rang et al., 2012). Cell-Cycle Phase-Specific Agents act in different points in the cycle. For example, Fluorouracil acts in S phase by disrupting DNA synthesis (Lehne, 2013). Cell-Cycle Phase Non-Specific Drugs are toxic during all phases of the cell cycle, including G0 (e.g. Cyclophosphamide and Epirubicin). Cell cycle non specific agents act on the cycle in or out of the cycle (Lennan, 2011).

publica-TFG-libro-ISBN

Fluorouracil (5FU) is a pyrimidine analogue, classified as an antimetabolite. Fluorouracil is converted into a FDUMP (fluorodeoxyuridine monophosphate) which inhibits the formation of thymidine aynthetase- an enzyme necessary for the synthesis of DNA (Wilkes and Barton-Burke, 2014). Fluorouracil is cell cycle phase-specific, acting during the S phase of cell division. Fluorouracil is known to work very well with other drugs in the adjuvant treatment of breast and colorectal cancer (Lehne, 2013).

Fluorouracil is metabolised by the liver and excreted by the kidneys and by the lungs as respiratory carbon dioxide. Liver function must be checked before each administration to ensure that no reduction of the dose is needed for patients with compromised liver function (Wilkes and Barton-Burke, 2014). Table 2 presents the side effects of Fluorouracil.

Epirubicin is antitumor antibiotic belonging to anthracyclines. They are cell-cycle phase non-specific (Wilkes and Barton-Burke, 2014). General properties of this drug include: damage of cells through direct interaction with DNA, intercalation of planar rings between DNA base pairs, DNA strand breakage and induce inhibition with the topoisomerase II- an enzyme responsible for uncoiling and repairing damaged DNA (Lehne, 2013). Epirubicin may also affect regulation of gene expression and produce free radical damage to DNA (Rang et al., 2012).

Epirubicin is metabolised by the liver, excreted through the biliary system and in the urine (Wilkes and Barton-Burke, 2014). Epirubicin can cause serious side effects as cardiac damage and bone marrow suppression (Lehne, 2013). Wilkes and Barton- Burke (2014) emphasize that «dose reductions should be made for patients with hepatic dysfunction and patients with severe renal dysfunction’. Epirubicin is a vesicant, can irritate veins, cause extravasation and tissue necrosis. The chemotherapy nurse is responsible for checking venous blood return at regular interval during administration of the drug (Dougherty and Lister, 2011). Table 3 illustrates the side effects of Epirubicin.

Cyclophosphamide is the most commonly used alkylating agent, classified as a nitrogen mustard (Rang et al., 2012). It works by preventing DNA synthesis and cell division through cross-linkage in DNA strands. Alkylating agents are cell cycle phase non-specific (Wilkes and Barton-Burke, 2014). Cyclophoshamide is not active as the parent drug, but in the liver, it is activated by enzymes to generate cytotoxic metabolites (Rang et al., 2012). Cyclophosphamide and its metabolites are excreted by the kidneys. Blood urea nitrogen and creatinine level must be checked prior to starting treatment Metabolites of the drug can irritate bladder wall capillaries and cause hemorrhagic cystitis (Lehne, 2013). Table 4 illustrates the side effects of Cyclophosphamide.

High fluid intake is recommended to avoid these side effects. Wilkes and Barton-Burke (2014, p.113) suggest at least 3 litres of fluid per day.

Selected chemotherapy drugs should be given in appropriate schedule. The interval between each cycle of chemotherapy is determined by the time taken for repair of bone marrow- every 21-28 days, to allow recovery of cells before the next cycle of cytotoxic agents (Lennan, 2011). In my practise my patient had FEC 75 at three weekly intervals. Prior to each cycle of chemotherapy patient had blood test to check blood count; including neutrophils and platelets count, liver and renal function. Twenty four hours after chemotherapy granulocyte colony stimulating factor was administered to stimulate the neutrophils. On day 10 after chemotherapy a nadir blood count is checked.

On assessing the above tables the most common side effect in this regimen is nausea and vomiting. When the cause of nausea and vomiting is a SACT, it is termed chemotherapy-induced nausea and vomiting (CINV) (Navari, 2013). I have chosen to focus on this topic because CINV is a very unpleasant symptom commonly experienced after chemotherapy. Nausea is defined by the National Cancer Institute (NCI, 2014) ‘as an unpleasant wavelike sensation in the back of the throat and/or the epigastrium that may culminate in vomiting‘. Vomiting is ‘the forceful expulsion of the contents of the stomach, duodenum through the oral cavity‘ (NCI, 2014). The pathophysiology of CINV is not completely understood. According to Stephens (2005, p.156) there are a lot of mechanisms responsible for CINV. Rang et al. (2012) explains that chemotherapy-induced nausea and vomiting are regulated by the stimulation of the vomiting centre and chemoreceptor trigger zone (CTZ) in the medulla. The diagram below (Figure 2) explains mechanisms of nausea and vomiting.

Chemotherapy-induced nausea and vomiting is classified as acute (occurs immediately after chemotherapy administration and lasting for up to 24 hours), delayed (occurs 24 hours after chemotherapy treatment) and anticipatory (occurs before chemotherapy administration) (Dikken and Wildman, 2013).

Wilkes and Barton-Burke (2014) indicated risk factors that affect the incidence of CINV. Such as: age (younger patients experience more nausea and vomiting than their older counterparts), gender (females have a higher incidence than males), drug dose and emetogenic potential (e.g. high dose of Cyclophosphamide can cause increase in the potential to induce CINV), history of alcohol intake (higher alcohol intake proves a positive effect of controlling emesis), anxiety, CINV during previous chemotherapy and severe emesis during pregnancy, which increases risk. The table below (Table 5) illustrates the emetogenic potential of selected chemotherapy drugs.

Combination chemotherapy is more effective to treat patients, however addition of two agents can increase the risk of CINV. For example Epirubicin and Cyclophosphamide are both moderately emetogenic, but when given together, the risk increases to highly emetogenic (Olver et al., 2011). Wilkes and Barton-Burke (2014, p.863) say that ‘it is much easier to prevent a patient’s nausea and vomiting than to try to control it afterwards‘. There are pharmacologic and non-pharmacologic management in CINV. Decision of anti-emetic drugs should be made according to the dose and emetic potential of anticancer drugs (Stephens, 2005).

Nausea and vomiting can be reduced by premedication with antiemetics based on emesis risk category. Effective control of emesis from the very first course of chemotherapy treatment will prevent the development of anticipatory nausea and vomiting and reduce risk of acute and delayed CINV (Perwitasari et al., 2011). The antiemetics drugs can be subdivided into seven major classes: serotonin antagonists (e.g. ondansetron, palanosetron), glucocorticoids (e.g. dexamethasone), substance P/neurokinin 1 antagononists (e.g. aprepitant), benzodiazepines (e.g. lorazepam), dopamine antagonists (e.g. haloperidol, metoclopramide), and anticholinergics (e.g. cyclizine) (Lehne, 2013).

According to Lehne (2013 p.1267) using a combination of antiemetics is much more effective than single-drug treatment. The Antiemetic Groups of the Multinational Association of Supportive care in Cancer (MASCC), American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN) provide an update of antiemetic guidelines in CINV management.

FEC chemotherapy regimens is classified as highly emetogenic. Chemotherapy drugs with high emetogenic risk have a greater than 90% incidence of nausea and vomiting. The Antiemetic Groups of the Multinational Association of Supportive care in Cancer (MASCC, 2013) and ASCO (Basch et al., 2011) agree that acute CINV in high emetogenic risk should be prevented with a serotonin receptor antagonists with dexamethasone and aprepitant. Guidelines for the prevention of delayed CINV in high emetogenic risk include dexamethasone and aprepitant on days 2 and 3 of chemotherapy cycle. The National Comprehensive Cancer Network (NCCN, 2014) guideline also include lorazepam as possible treatment of acute and delayed chemotherapy-induced nausea and vomiting.

Serotonin receptor antagonists are the most effective drugs available for prevention of CINV caused by highly emetogenic anticancer drugs. Ondasetron works by blocking type 3 serotonin receptors (5-HT3 receptors) located in the chemoreceptor trigger zone (CTZ) in the medulla and in the upper gastrointestinal tract. Ondasetron is more effective when combined with dexamethasone (Feyer and Jordan, 2011). Palanosetron has the same mechanism as other serotonin receptor antagonists but much longer half-life. It can prevent delayed CINV as well as acute CINV (Affronti and Bubalo, 2014).

Dexamethasone is corticosteroid commonly used in acute and delayed CINV. Dexamethasone is more effective when given in combination with ondasetron and aprepitant. The mechanism by which glucocorticoids prevent CINV is not completely understood (Kris et al., 2011). Wilkes and Barton-Burke (2014 p.863) think it is related to an anti-inflammatory effect.

Aprepitant works by blocking neurokinin 1- type receptors (for substance P) located in the chemoreceptor trigger zone. Aprepitant has a pronolged duration of action and can be used in acute and delayed CINV (Wilkes and Barton-Burke, 2014).

Lorazepam is a benzodiazepine, commonly used in suppression of anticipatory CINV. It can help control acute and delayed emesis by sedation and production of amnesia, allowing then to forget the sensation of nausea (Lehne, 2013).

Non-pharmacologic interventions are suitable for management of CINV, education, special diet, exercises, and complementary therapies (Stern et al., 2011). Acupressure and use of ‘sea-bands’ have been reported to relieve nausea (Suh, 2012). CINV does not only have physical implications. It may have impact on patient’s quality of life and cause social isolation, lack of energy, feeling helpless and dehydrated. Potential problems related to nausea and vomiting can contribute to fatigue and depression (Fernandez-Ortega, 2012). If patient has poorly controlled CINV, hospitalisation and intravenous fluids and intravenous antiemetics may be required (Vidall, 2011). Nurses play an important role in assisting patients this side effect by education and support (Bourdeanu and Dee, 2013).

In conclusion, in this essay, I have discussed FEC 75 chemotherapy regimen, the principles and its mode of action. I also identified the short and long term side effects of this regimen. I also discussed the most common side, chemotherapy-induced nausea and vomiting (CINV). I exploring its physiology, classification, potential risk factors and evidence-based analysis of pharmacologic and non-pharmacologic management of CINV as well as the impact of this symptom on the patients.

Table 1. Examples of chemotherapeutic agents used to treat breast cancer (Lennan, 2011, p. 156).

Table 2. Side effects of Fluorouracil (Dougherty, McWhirter and Jones, 2014, p. 82).

Table 3. Side effects of Epirubicin (Dougherty, McWhirter and Jones, 2014, p. 73).

Table 4. Side effects of Cyclophosphamide (Dougherty, McWhirter and Jones, 2014, p. 60).

Table 5. Emetogenic Potential of Selected Intravenous Anticancer Drugs (Lehne, 2013, p. 1267).

Figure 1. Mechanism of action of major chemotherapy drugs (Wilkes and Barton-Burke, 2014, p. 3).

Figures – FEC 75 and Nausea and vomiting

Figures – FEC 75 and Nausea and vomiting.pdf

Figure 2. The Physiology of Nausea and Vomiting (Wilkes and Barton-Burke, 2014, p. 864).

FEC-75-nausea-vomiting

References:

Affronti, M.L. and Bubalo, J. (2014) ‘Palonosetron in the management of chemotherapy-induced nausea and vomiting in patients receiving multiple-day chemotherapy’, Cancer Management and Research, 6, pp. 329-337.

Almeida, C.A. and Barry, S.A. (2010) Cancer: Basic Science and Clinical Aspects. Oxford: Wiley-Blackwell.

Basch, E., Prestrud, A.A., Hesketh, P.J. et al. (2011) ‘Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update’, Journal of Clinical Oncology, 29 (31), pp. 4189-4199.

Bourdeanu, L. and Dee, V. (2013) ‘Assessment of Chemotherapy Induced Nausea and Vomiting in Women with Breast Cancer: A Neuman Systems Model Framework’, Research and Theory for Nursing Practice: An International Journal, 27 (4), pp. 296- 304.

Cassidy, J., Bissett, D., Spence, R.A.J. and Payne, M. (2010) Oxford Handbook of Oncology. 3rd edn. New York: Oxford University Press.

Dikken, C. and Wildman, K. (2013) ‘Control of nausea and vomiting caused by chemotherapy’, Cancer Nursing Practice, 12 (8), pp. 24-29.

Dougherty, L. and Lister, S. (2011) Chapter 15: Cytotoxic therapy. The Royal Marsden Hospital Manual of Clinical Nursing Procedures. 8th edn. Oxford: Wiley-Blackwell, pp. 870-931

Dougherty, L., McWhirter A. & Jones P. (2014) Handbook of systemic treatment for cancer. Lilly Oncology UK. 8th edn. Teddington: Haymarket Medical.

Eadens, M. and Ajithkumar, T. (2011) ‘Early stage breast cancer: adjuvant systemic treatment’, in Ajithkumar, T., Barrett, A., Hatcher, H. and Cook, N. (ed) Oxford Desk Reference Oncology. New York: Oxford University Press, pp. 162-164.

Fernandez-Ortega, P., Caloto, M.T., Chirveches, E. et al. (2012) ‘Chemotherapy- induced nausea and vomiting in clinical practice: impact of patient’s quality of life’, Supportive Care in Cancer, 20 (12), pp. 3141-8.

Feyer, P. and Jordan, K. (2011) ‘Update and new trends in antiemetic therapy: the continuing need for novel therapies’, Annals of Oncology, 22 (1), pp. 20-38.

Grimsey, E. (2011) ‘An overview of the breast and breast cancer’ in Harmer, V. (ed) Breast Cancer Nursing Care and Management. 7th edn. Oxford: Wiley-Blackwell, pp. 1-18.

Johnston, S.R.D. (2005) ‘Systemic therapy for breast cancer’ in Brighton, D., Wood, M., Johnston, S.R.D, Ford, H. and Ross, P.J. (ed) The Royal Marsden Hospital Handbook of Cancer Chemotherapy. Edinburgh: Elsevier Churchill Livingstone, pp. 273-291.

Kris, M.G., Tonato, M., Bria, E. et al. (2011) ‘Consensus recommendations for the prevention of vomiting and nausea following high-emetic-risk chemotherapy’ Support Care Cancer, 19 (1), pp. 25-32.

Lehne, R.A. (2013) Pharmacology for Nursing Care. 8th edn. Missouri: Elsevier Saunders.

Lenann, E. (2011) ‘Chemotherapy as a treatment for breast cancer’ in Harmer, V. (ed) Breast Cancer Nursing Care and Management. 7th edn. Oxford: Wiley-Blackwell, pp. 149-172.

Lua, P.L and Zakaria, N.S. (2012) ‘A Brief Review of Current Scientific Evidence Involving Aromatherapy Use for Nausea and Vomiting’, The Journal of Alternative and Complementary Medicine, 18 (6), pp. 534-540.

Multinational Association of Supportive care in Cancer (2013) Antiemetic guidelines. Available at: http://www.mascc.org (Accessed: 20 February 2015).

National Cancer Institute (2014) Nausea and Vomiting. Available at http://www.cancer.gov (Accessed: 20 February 2015).

National Comprehensive Cancer Network (2014) Antiemetic guidelines. Available at http://www.nccn.org (Accessed: 4 March 2015).

Navari, R.M. (2013) ‘Management of Chemotherapy-Induced Nausea and Vomiting: Focus on Newer Agents and New Uses for Older Agents’, Drugs, 73 (3), pp. 249-262.

Olver, I., Molassiotis, A., Aapro, M. et al. (2011) ‘Antiemetic research: future directions’, Support Care Cancer, 19 (1), pp.49-55.

Perwitasari, D.A., Gelderblom, H., Atthobari, J. et al. (2011) ‘Anti-emetic drugs in oncology: pharmacology and individualization by pharmacogenetics’, Int J Clin Pharm, 33, pp. 33-43.

Rang, H.P., Dale, M.M, Ritter, J.M., Flower, R.J. and Henderson, G. (2012) Pharmacology. 7th edn. London: Elsevier Churchill Livingstone.

Stephens, M. (2005) ‘Nausea and vomiting’ in Brighton, D., Wood, M., Johnston, S.R.D, Ford, H. and Ross, P.J. (ed) The Royal Marsden Hospital Handbook of Cancer Chemotherapy. Edinburgh: Elsevier Churchill Livingstone, pp. 155-160.

Stern, R.M., Koch, K.L. and Andrews, P.L.R. (2011) Nausea: mechanism and managment. New York: Oxford University Press.

Suh, E.E., (2012) ‘The effects of P6 Acupressure and Nurse-Provided Counseling on Chemotherapy-Induced Nausea and Vomiting in Patients with Breast Cancer’, Oncology Nursing Forum, 39 (1), pp. 1-9.

Wilkes, G.M. and Barton-Burke, M. (2014) Oncology nursing drug handbook. Burlington: Jones & Bartlett Publishers.

Vidall, C. (2011) ‘CINV in the UK: a prospective audit of patients experience’, British Journal of Nursing, 20 (10), pp. 29-31.

close

BOLETÍN DE NOVEDADES

Datos opcionales:

(En ocasiones enviamos información específica para una zona o categoría concreta)

He leído y acepto la Política de Privacidad *

Ver Política de Privacidad y Aviso legal

Su dirección de e-mail solo se utilizará para enviarle nuestra newsletter, así como información sobre las novedades de la revista y Editorial Ocronos. Puede utilizar el enlace integrado en la newsletter para cancelar la suscripción en cualquier momento.