Diarrhoea induced by anticancer drugs is common and can cause morbidity and mortality: grade 3–4 serious adverse events are reported with a frequency of 5–47% in randomized clinical trials (Andreyev et al. [4]). As a result treatment is frequently compromised as diarrhoea can sometimes lead to hospital admission and can be life threatening. Clinical trials have reported death due to fluorouracil‐induced diarrhoea in 1–5% of patients (Tveit et al. [289]). Chemotherapy‐induced diarrhoea remains an important complication and the risk of death is increased when the patient is also neutropenic (Andreyev et al. [4]). Chemotherapeutic agents frequently associated with diarrhoea are listed in Table 26.7 although this is not exhaustive and the toxic effects depend on the schedule and dose of the drug.

Working within the acute cancer care setting, an understanding of the main treatments used helps the nurse to predict the likely cause of the patient's symptoms. The following information provides examples of how practical knowledge of GI side‐effects of anticancer treatment can assist the cancer nurse to better support patients through treatment and recognize side‐effects early.

Although radiotherapy is discussed in detail in Chapter c24, it is important to highlight this treatment modality here because diarrhoea is a common adverse event. The severity of acute GI symptoms during pelvic radiation depends partly on the dose given and volume of bowel treated; other risk factors include diabetes, inflammatory bowel disease, collagen vascular disease, HIV, old age, smoking and low body mass index (Fuccio et al. [87]). Acute intestinal side‐effects of radiation begin at approximately 10–20 Gy and peak between weeks 3 and 5 of treatment (Faithfull [72]). Acute diarrhoea is an independent prognostic factor of outcome during treatment for colorectal cancer, but more severe acute effects are also associated with long‐term consequences of treatment (Bowen [22]).

The seriousness of diarrhoea is frequently defined using the common terminology criteria for adverse events (CTCAE; US Department of Health and Human Services [296]) (Table 26.8).

The most important decision is whether the patient can be managed as an outpatient or needs admission for fluid resuscitation; this depends on the risk of adverse outcomes. Patients with grade 1–2 diarrhoea without worrying clinical features and test results can usually be managed at home. Those with grade 3–4 diarrhoea generally need immediate admission unless clinical review suggests the patient is well hydrated, has not yet had any antidiarrhoeal medication, and can be reviewed daily (Andreyev et al. [4]). Several features should alert clinicians to the fact that diarrhoea is clinically worrying, including abdominal cramps not relieved by loperamide, an inability to eat, increasing fatigue, increasing weakness, chest pain, nausea not controlled by antiemetics, vomiting, dehydration accompanied by reduced urine output, fever (temperature higher than 38.5°C), gastrointestinal bleeding and previous admission for diarrhoea.

If an acute oncology helpline is available, the patient should be encouraged to telephone for advice after starting antidiarrhoeal medication to confirm the severity and whether face‐to‐face assessment is required.

Guidance in the UK on the management of GI side‐effects of cancer therapies emphasizes three crucial factors:

Other important factors to consider are:

Patients can be encouraged to self‐medicate but should keep a record of their drug use. How much to take, how often, and when in relation to meals patients can take antidiarrhoeal medication must be made clear if patients are to keep medications at home (Andreyev et al. [4]). For CID it is important to determine if the patient is currently taking any oral chemotherapy; if they are, they should be advised to stop taking it and commence oral loperamide (UKONS [294]). Importantly, if the first dose of loperamide does not work, patients should be informed that it is likely that they have not taken enough. After starting loperamide, patients need to know when they must contact their chemotherapy unit and when they can delay contact; generally, patients should make contact if taking eight 2 mg tablets in 24 hours has had no effect as they may need intravenous fluids and other treatments (Andreyev et al. [4]). A starting dose of 4 mg followed by 2 mg every 2 h after an episode of diarrhoea is often recommended. If the patient can still eat, however, this treatment might be more effective if taken 30 minutes before food (Benson et al. [18], Nightingale et al. [213], Remington et al. [247]).

Loperamide can be discontinued when the patient has been diarrhoea free for 12 hours (Benson et al. [18]). If mild to moderate diarrhoea persists for more than 24 hours, high‐dose loperamide may be given and oral antibiotics should be initiated as prophylaxis against infection (Benson et al. [18], Cherny [35]). If mild to moderate CID persists for more than 48 hours while the patient is on high‐dose loperamide, loperamide should be discontinued and a second‐line antidiarrhoeal agent should be started, such as octreotide (starting at 100–150 µg subcutaneously [SC]) (Benson et al. [18], Muehlbauer et al. [191]).

Complicated cases of CID require aggressive treatment involving hospitalization and intravenous fluids (Cherny [35]). Higher doses of loperamide have not been shown to be effective for grade 3–4 CID, and a change to octreotide 100–150 µg (SC or intravenous [IV]) with a dose escalation up to 500 µg until diarrhoea is controlled should be considered (Benson et al. [18], Muehlbauer et al. [191]). Patients can become dehydrated because of diarrhoea with or without vomiting but the physiological requirements must be established before and reviewed regularly after replacement of fluids is started (Andreyev et al. [4]). Patients with severe CID can lose up to 4–6 L of diarrhoea per day, putting them at risk of becoming severely hypovolaemic, which can make exclusion or differentiation from sepsis difficult (they might coincide). If hypovolaemia is uncertain, the response to a 500 mL bolus (250 mL in patients with a history of cardiac failure) of a balanced crystalloid (0.9% sodium chloride is preferred if potassium concentrations are higher than 5.5 mmol/L or if oliguric AKI is possible) should be assessed to see if blood plasma volume increases (Benson et al. [18]). In severely ill patients who are hypotensive, tachycardic and potentially septic and have high lactate concentrations, an initial fluid bolus of 20 mL/kg should be given (Rivers et al. [252]). Consensus guidelines (Figure 26.4) have been produced to support evidence‐based practice in this growing problem.

The initial treatment for mild to moderate diarrhoea includes non‐pharmacological interventions. Dietary modifications such as eliminating all lactose‐containing products, alcohol and high‐osmolar dietary supplements may help decrease CID. Sorbitol‐containing products, such as sugar‐free gum and confectionery, should be eliminated as they can cause diarrhoea (Muehlbauer et al. [191]). Any medications or foods that may enhance the diarrhoea should be discontinued. The patient should be instructed to document stool frequency and promptly report symptoms of fever or dizziness upon standing (Benson et al. [18], Cherny [35]). Other non‐pharmacological interventions include hydrating with 8–10 glasses of clear liquids per day and eating small frequent meals (Benson et al. [18]). Oral rehydration with fluids that contain water, sugar and salt will help prevent hyponatraemia and hypokalaemia; such fluids are sports drinks, broth, gelatine and decaffeinated, decarbonated soft drinks (Benson et al. [18], Richardson and Dobish [249]).

Autoimmune colitis (enterocolitis) requires different management to other forms of treatment‐induced diarrhoea. This is due to the mode of action of the monoclonal antibodies that work using the body's immune response such as ipilimumab. The severity of side‐effects is directly correlated to the treatment dose (Fecher et al. [75]). Therefore, ascertaining the patient's current treatment modality (specifically the drug) is imperative in being able to manage the type of treatment‐induced diarrhoea. For the purposes of this section the drug ipilimumab will be used as this is most commonly used in practice. Ipilimumab‐related diarrhoea of any grade is reported in approximately 30–35% of patients, and grade 3–5 diarrhoea or enterocolitis in 5–8% (Hodi et al. [110]). Mild, intermittent changes in bowel movements are commonly seen with this drug, therefore all diarrhoea is suspect and most likely related to the drug.

As with all treatment‐induced diarrhoea, patient education will ensure that diarrhoea is reported and managed promptly. It can be self‐limited; however, ipilimumab‐related diarrhoea is not typical of the drug‐induced or idiopathic diarrhoea seen with other cancer therapies. It often presents around the second dose of therapy, but its timing of onset can vary and is not predictable. Symptoms can progress rapidly to potentially life‐threatening status if untreated (Fecher et al. [75]). If a diagnosis of ipilimumab‐induced colitis is established, treatment should be initiated with oral or IV steroids, depending on the grade of diarrhoea. Once an intervention is initiated, reassessment within 24 hours in the hospital or by telephone is necessary. Frequent re‐evaluation is recommended as symptoms and course can change rapidly and response to interventions cannot be assumed. Referral to a gastroenterologist for flexible sigmoidoscopy or colonoscopy should be considered for persistent grade 2 diarrhoea or any grade 3–4 diarrhoea.

Patients presenting with grade 3–4 diarrhoea may need hospital admission for work‐up, monitoring, IV hydration, bowel rest (nil by mouth) and high‐dose IV steroids. For patients with refractory symptoms despite maximal medical support and treatment with high‐dose steroids for approximately 5 days, a single dose of infliximab 5 mg/kg has demonstrated rapid resolution of symptoms and durable efficacy and should be considered (Johnston et al. [121]). Infliximab may also be considered for persistent grade 2 symptoms that do not resolve despite treatment with steroids. Infliximab can be repeated, but should not be used if there is concern for perforation or sepsis. The immune‐related adverse event (irAE) gastrointestinal management algorithm (Figure 26.5) sets out what steps should be taken in the management of ipilimumab‐induced gastrointestinal toxicities.