Myeloma Nurse Learning Programme Module 8 – Management of disease and treatment-related symptoms and complications in myeloma Gastrointestinal toxicities

Gastrointestinal toxicities

Gastrointestinal toxicity refers to the adverse reaction of a drug on the digestive system. In myeloma, many of the anti-myeloma and supportive treatments (chemotherapy, bisphosphonates, bortezomib, thalidomide and lenalidomide, opioid-based analgesia, radiotherapy) are associated with gastrointestinal side effects. They can also be a result of other conditions such as hypercalcaemia, infections and stress.

These side effects can present as one or more of the following:

Nausea
Vomiting
Diarrhoea
Constipation
Loss of appetite

Without appropriate treatment and management, these side effects can compromise treatment compliance, impact significantly on quality of life and in some cases, even be life-threatening. The effects of gastrointestinal side effects can have also have a significant psychological impact, therefore prompt intervention and effective management are crucial to maintaining optimum outcomes for patients.

Nurses play a pivotal role in the assessment, medical and non-medical management of gastrointestinal side effects and can have a considerable impact on the care of patients with these problems. Read more about how to help your patients manage these side effects in our Myeloma Nurse Guide: Gastrointestinal toxicities.

Assessment of gastrointestinal toxicities

Signs and symptoms of gastrointestinal toxicity can be recognised but for the most part, rely on patients reporting. Nurses have a key role in educating patients on the importance of reporting gastrointestinal issues and the potential implications if they are left unchecked.

A medical history, physical assessments, blood and stool tests should be carried out where appropriate to identify the cause of the GI toxicity. The severity of nausea, vomiting, diarrhoea and constipation can be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE Version 5.0, Table 6). Events that are greater than grade 2 should be referred for further attention.

Table 6: Grading of GI toxicity, NCI CTCAE (5.0)

Gastrointestinal event	Grade 1	Grade 2	Grade 3	Grade 4	Grade 5
Constipation	Occasional or intermittent symptoms; occasional use of stool softeners, laxatives, dietary modification, or enema	Persistent symptoms with regular use of laxatives or enemas; limiting instrumental ADL	Obstipation with manual evacuation indicated; limiting self-care ADL	Life-threatening consequences; urgent intervention indicated	Death
Diarrhoea	Increase of <4 stools per day over baseline; mild increase in ostomy output compared to baseline	Increase of 4 – 6 stools per day over baseline; moderate increase in ostomy output compared to baseline	Increase of ≥ 7 stools per day over baseline; incontinence; hospitalisation indicated; severe increase in ostomy output compared to baseline; limiting self care ADL	Life-threatening consequences; urgent intervention indicated	Death
Nausea	Loss of appetite without alteration in eating habits	Oral intake decreased without significant weight loss, dehydration or malnutrition	Inadequate oral caloric or fluid intake; tube feeding, TPN, or hospitalization indicated
Vomiting	1 – 2 episodes (separated by 5 minutes) in 24 hrs	3 – 5 episodes (separated by 5 minutes) in 24 hrs	≥ 6 episodes (separated by 5 minutes) in 24 hrs; tube feeding, TPN or hospitalisation indicated	Life-threatening consequences; urgent intervention indicated	Death

Treatment for gastrointestinal toxicity

Drug treatments may be appropriate for some patients depending on the nature and severity of their gastrointestinal problem.

Treatment for nausea and vomiting

Anti-emetics are usually effective against vomiting and nausea and are always given prior to and during the administration of chemotherapy. They can be given orally, intravenously or rectally.

Depending on the anticipated risk of nausea and vomiting associated with treatment and/or ongoing problems, different drugs may be used. For patients undergoing systemic anti-cancer treatment (SACT), ondansetron is often the first line choice, although constipation is a common and potentially serious side effect of its use. If not on chemotherapy, metoclopramide given orally or intravenously can be used, with diarrhoea as a monitored side effect. Metoclopramide can also be used alongside ondansetron for patients on SACT as a breakthrough anti emetic. Cyclizine can be used as an alternative to metoclopramide but these two drugs should not be used in tandem as they have an antagonistic effect.

Patients with continued nausea and vomiting may be treated with haloperidol or levomepromazine, which can cause side effects such as disorientation or confusion. Those with severe vomiting may also need intravenous hydration, electrolyte replacement and in extreme cases, parenteral nutrition.

Anticipatory nausea or vomiting is a common phenomenon. It occurs because of a learned response where patients, who previously vomited after treatment, subconsciously anticipate that nausea and vomiting is inevitable when they restart treatment. This can be triggered by thoughts of the treatment, smells, environments etc. For these patients, an anxiolytic such as lorazepam or complementary therapies such as guided imagery, hypnosis, alternative therapies such as acupuncture and distraction, may be helpful.

Treatment for diarrhoea

For patients who have mild diarrhoea that persists for more than 24 hours, anti-diarrhoeal treatments such as loperamide may help. Patients who have diarrhoea whilst on bortezomib or lenalidomide must seek advice quickly. Lenalidomide can cause bile acid malabsorption which must be diagnosed by a nuclear medicine SeHCAT (Tauroselcholic [75selenium] acid) scan. Symptoms of this condition, including diarrhoea, can be improved by a low-fat diet and/or treatment with colosevelam, a bile acid sequestrant. A referral to gastroenterology may be required.

Aggressive fluid and electrolyte replacement may be needed for severe cases of diarrhoea (> 7 stools per day over baseline), and/or a change in dose or pause in myeloma treatment.

Treatment for constipation

Constipation, either as a side effect of anti-myeloma treatments or supportive care drugs, must be taken seriously in myeloma patients due to the risks associated with myelosuppression. Treatment for constipation includes the use of stool softeners e.g. Movicol® or lactulose, and other laxatives. Patients with severe constipation may require rectal measures (suppositories, enemas, manual evacuation) but note that these are very often contraindicated due to infection and bleeding risks in patients with myeloma. Therefore, proactive early management of constipation is crucial alongside careful patient education.

Recommendations for the prevention and management of constipation, diarrhoea, nausea and vomiting are summarised in Table 7.

Table 7: Recommendations for the management of GI side effects

Constipation	Diarrhoea	Nausea	Vomiting
Increase fluid intake Increase fibre intake Take gentle exercise Laxative and stimulant medications	Increase fluid intake (8–10 cups daily): water, electrolyte-replacement beverages, sports drinks, diluted fruit juices, and broth Avoid caffeinated, carbonated, heavily sugared beverages, alcohol, fruit juices with pulp, high-fibre and high-fat foods, hot or heavily spiced foods, dairy products Use skin barrier products (with caution): vitamin D ointment, nappy-rash cream, or other moisture-barrier products Antidiarrhoeal agent, e.g. loperamide	Mild anti-nausea medications the night before treatment Oral medication dosing For severe nausea follow ‘vomiting’ recommendations	Pre-operative oral anti-emetic Cool, damp cloth to the forehead, neck, and wrists Restrict fluid with meals Try peppermint or ginger tea, a sports beverage, ice cubes/lollies Eat small, frequent meals Eat bland, cold, or room temperature food such as crackers, toast, cereals, and ginger biscuits Avoid sweet, salty, fatty, and spicy foods Avoid citrus and tomatoes

N.B. A stool culture is recommended for patients with diarrhoea to rule out C.difficile or other infections. Nurses should advise their patients that over-the-counter anti-diarrhoeal drugs should not be used without first consulting a clinician because of the possibility that diarrhoea may be caused by an infection.

Proactive nursing interventions and management are key to reducing the impact and severity of the distressing symptoms and improving quality of life and outcomes for patients.