Cancer and its treatments may cause mucositis, nausea, vomiting, diarrhoea and constipation. Pharmacological treatments and dietary recommendations can prevent and treat these disorders
Jean-Baptiste Rey PharmD PhD
Institut de Cancérologie Jean Godinot
Département de Pharmacie
Rue du Général Koenig – 51100 Reims, France
Mathilde Brasseur MD
Centre Hospitalier de Soissons
Unité d’hospitalisation de jour
Avenue du Général De Gaulle – 02200 Soissons, France
email: [email protected]
In patients with cancer, the entire digestive tract can undergo a number of disorders. From the mouth to the anus, complications are multiple; the major ones include:
- Nausea and vomiting
- Diarrhoea or constipation
These gastrointestinal complications are caused by the cancer itself, but also by the specific treatments used, chemotherapy and radiotherapy in particular. This article presents various gastrointestinal disorders that may occur in patients with cancer and during treatment, as well as curative and preventive treatments that can be implemented.
Mucositis is an inflammation of the mucosa that covers the inside cavities and viscera. It is most often caused by the treatment. Radiotherapy and chemotherapy cause radiation-induced and chemotherapy-induced mucositis, respectively. In the initial phase, there is a reddening of the mucosa progressing to painful ulcerations that may compromise oral nutrition or hydration and evolve to necrosis. These lesions are a gateway for microorganisms such as bacteria (mainly gram-positive cocci), fungi (Candida) and/or viruses (20–30% of cases of mucositis have a viral component, mainly herpes simplex virus – HSV-1 and HSV-2) and can cause systemic infections especially in the case of neutropenia.
These disorders affect 20–80% of patients depending on the intensity of treatment.1 The management of mucositis is based on the recommendations of the Multinational Association for Supportive Care in Cancer (MASCC), which was recently published. They differentiate mucositis of the oral cavity from mucositis of the gastrointestinal tract. For diseases of the mouth recommendations are summarised in Figure 1 and they distinguish recommended treatments, possible treatments and treatments that are not recommended.2
Patients should be educated in oral hygiene and dietary advice is essential at the beginning and throughout the care of the patient for prevention of those lesions.
Nausea and vomiting
Nausea and vomiting are one of the most feared side effects of chemotherapy; the management of this adverse effect is simple since it is based on the recommendations of societies (including the joint MASCC/ESMO recommendations).3 For each chemotherapy regimen and also radiation oncology procedures (radiation-induced nausea and vomiting), the experts defined a level of emetogenicity (very low, low, moderate and highly emetogenic) and the standard care to be implemented in each case. It is based on the different antiemetic drugs available on the market. Thus, the role of anti-NK1 (for example, aprepitant netupitant), anti-5HT3 (for example, palonosetron, ondansetron), anti-D2 (for example, metoclopramide) and corticosteroids (for example, dexamethasone) is established with pre-formatted regimens according to the nature of nausea and vomiting (acute: in the first 24 hours following chemotherapy; delayed phase: between the 24th and the 120th hour or beyond; following chemotherapy; anticipatory nausea and vomiting: occurring before the administration of anticancer drugs). In addition, this publication provides guidance for the use of “rescue” treatments, used for refractory nausea and vomiting.3
Prevention of acute and delayed nausea and vomiting is summarised in Figures 2 and 3.
Following these recommendations strictly provides an antiemetic control (no vomiting and nausea grade 0 or 1 according to the NCI-CTCAE4) in the vast majority of patients (approximately 90%).
Many cytotoxic drugs (irinotecan especially, but also 5FU) and targeted therapies (tyrosine kinase inhibitors – TKI) sometimes cause severe diarrhoea, which may require hospitalisation especially when oral hydration is compromised (associated vomiting). They may involve the vital prognosis of patients with induced electrolyte disorders (acute renal failure, hypokalemia). In the particular case of TKI, those that target EGFR and are administered orally (afatinib, gefitinib, erlotinib) cause more diarrhoea than those which target other signalling pathways (HER2, VEGF). However, the incidence of diarrhoea is very important with these new therapeutic agents, whatever the target.
In the particular case of irinotecan, the diarrhoea may be early, occurring during the infusion: acute cholinergic syndrome is treated and prevented by subcutaneous administration of atropine. The other type of irinotecan-induced diarrhoea is delayed diarrhoea requiring preventive patient education (regarding adequate hydration) and curative treatment with loperamide (up to one capsule every two hours). There is no preventive treatment of diarrhoea but the patient under treatment at risk must have a prescription for “loperamide in case of diarrhoea”. Loperamide acts on the µ-receptors in the intestinal mucosa. This leads to a decrease in gastrointestinal motility by decreasing the circular and longitudinal smooth muscle activity of the intestinal wall. This slows intestinal transit and allows for more water and electrolyte absorption from the intestines.5
On the other hand, constipation is not uncommon in patients with cancer. Beyond occlusive syndromes of peritoneal carcinomatosis, it is the opioid drugs (weak opioids such as codeine, hydrocodone and dihydrocodeine; strong opioids such as morphine, oxycodone, fentanyl, hydromorphone, nalbuphine and pethidine6) that are responsible for constipation. Constipation is defined as a decrease in stool frequency and/or a change in consistency.
It is essential to prevent the constipation induced by opioids; constipation might be complicated by intestinal obstruction. It is directly related to the mechanism of action of opioid analgesics by stimulation of intestinal peripheral μ-receptors. Thus, patients should be advised to hydrate, eat vegetables and fibre, and if possible to do mild exercise, but also to take their routine prescription laxatives with these opioid therapies. The osmotic laxatives are ideally administered orally, but oral lubricant laxatives or microenemas (rectal) may also be employed.
In refractory constipation, not yielding to oral laxatives or enemas, and in the absence of mechanical obstruction syndrome (which is a contraindication), it is possible to treat with peripheral μ-receptor antagonist, methylnaltrexone (analogue of naloxone, opioids central antidote) administered subcutaneously every 24–48 hours.7 Generally constipation is relieved within a few hours of administration, however this indication is very limited.
Gastrointestinal disorders are common in oncology. Preventative or curative measures exist to deal with them. They help the continuation of the cancer treatment, as well as supportive care treatments such as pain management, and to avoid delays in administration or dosage reductions of cancer drugs or worse, treatment interruptions. The implementation of these simple and inexpensive measures can only be beneficial for patients.
- Gastrointestinal conditions can delay or compromise cancer treatment.
- Mucositis-, chemotherapy- and radiotherapy-induced nausea and vomiting, diarrhoea and/ or constipation are constant in cancer patients.
- Recommendations exist and are easily avalaible to prevent and treat these disorders.
- Prevention and treatment measures are simple, not expensive and cost-effective; they allow specific cancer treatments to continue at optimal dosage.
- The digestive system. www.webmd.com/digestive-disorders/digestive-system (accessed 6 November 2014).
- Lalla RV et al. MASCC / ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer 2014;120:2657–64.
- Roila F et al. Guideline update for MASCC and ESMO in the prevention of chemotherapy and radiotherapy-induced nausea and vomiting: results of the Perugia consensus conference. Ann Oncol 2010;21(Supp 5):232–43.
- U.S. Department Of Health And Human Services. National Institutes of Health. National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE): http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf (accessed 6 November 2014).
- US National Cancer Institute, Drug Dictionary – Loperamide hydrochloride. http://www.cancer.gov/drugdictionary?CdrID=41911 (accessed 6 November 2014).
- Anonymous (1990). Cancer pain relief and palliative care; report of a WHO expert committee. World Health Organization Technical Report Series, 804. Geneva, Switzerland: World Health Organization. pp. 1–75.
- Relistor – Summary of Product Characteristics: http://labeling.pfizer.com/showlabeling.aspx?id=499 (accessed 6 November 2014).