Supportive care options for cancer

Managing side effects associated with chemotherapy and radiation therapy

Chemotherapy drugs are used extensively in clinic as one of the main cancer treatments and can be administered alone or as adjuvant therapy. Chemotherapy interferes with and inhibits DNA, RNA and protein synthesis, often in the S phase of the cell cycle, leading to cell death. Radiation therapy is commonly used in conjunction with chemotherapy and has a similar mode of action, causing damage to DNA strands and resulting in cell death¹.

Although chemotherapy and radiation therapy have improved the survival of people with cancer, they are notorious for causing severe side effects that ultimately limit the amount that can be tolerated and, thus, treatment efficacy¹

Drugs commonly used for chemotherapy include¹:

• Platinum-based agents (cisplatin, oxaliplatin, carboplatin)
• Taxanes (paclitaxel, docetaxel)
• Fluoropyrimidines (5-fluorouracil, capecitabine)
• Vinca alkaloids (vinblastine, vinorelbine, vincristine, vindesine)  

Guideline recommendations for managing the side effects of chemotherapy and radiation therapy

Fatigue

Dr Gary Lyman (Fred Hutchinson Cancer Center, Seattle, Washington, USA) discusses guideline-recommended approaches to managing fatigue in people with cancer. View transcript

Management of cancer-related fatigue includes an initial screening for contributing factors such as sleep disturbance and anaemia². Management interventions include exercise (a mixture of aerobic, strength and flexibility exercises), cognitive behavioural therapy, and pharmacological management with psychostimulants such as methylphenidate and dexamphetamine².

Thrombosis

Dr Lyman discusses the challenges of treating thrombosis in people with cancer. View transcript

Venous thromboembolism (VTE) is a major complication of cancer. Anticoagulants are used for VTE prevention, and treatment options include^3-8:

• Unfractionated heparin (UFH)
• Low-molecular-weight heparins (LMWHs)
• Fondaparinux (a synthetic indirect inhibitor of activated factor Xa)
• Vitamin K antagonists (VKAs)
• Direct oral anticoagulants (DOACS)

Choice of anticoagulant is determined by considerations such as bleeding risk, patient preference and potential drug interactions^4-8. LMWH is the preferred treatment choice in those at high risk of bleeding, while for patients at low risk of bleeding, DOACs (apixaban or rivaroxaban) are preferred^4-8. Caution should be exercised when prescribing DOACS to people with gastrointestinal or genitourinary tract cancers because of an increased risk of bleeding^4,5,7,8. If apixaban, rivaroxaban or LMWHs are contraindicated or unsuitable, alternatives such as dabigatran, UFH, fondaparinux or a VKA can be considered⁵.

For symptomatic or incidental VTE, treatment is recommended for at least 3–6 months, or for as long as the cancer is active, the patient remains on cancer therapy or remains at high risk of recurrent VTE^5,6.

The American Society of Hematology (ASH) 2021 guidelines suggest indefinite anticoagulant treatment for the long-term prevention of VTE in patients with cancer may be considered if the benefits outweigh the risks⁵. Similarly, the European Society for Medical Oncology (ESMO) 2023 guidelines and American Society of Clinical Oncology (ASCO) 2023 guidelines suggest extending anticoagulant treatment beyond 6 months in patients in whom the risk of recurrence outweighs the risks of bleeding complications, and that the risk–benefit profile should be regularly reassessed^6,9.

Chemotherapy-induced thrombocytopenia

The National Comprehensive Cancer Network (NCCN) 2024 guidelines recommend considering platelet transfusion, chemotherapy dose reduction or regimen change, or a thrombopoietin receptor agonist (TPO-RA) within a clinical trial as treatment¹⁰. The International Society on Thrombosis and Haemostasis (ISTH) similarly recommend platelet transfusion for severe chemotherapy-induced thrombocytopenia (CIT) or a TPO-RA as part of a clinical trial for CIT in people with solid tumours, with the goal of TPO-RA use to achieve an adequate platelet count and avoid reductions in chemotherapy dose intensity in future cycles¹¹.

Platelet transfusion remains the cornerstone of managing CIT; however, potential problems including allogeneic immunity, infectious pathogen transfer and transfusion reactions need to be considered^11,12. A synthesis of the available data on management practices is as follows^10,11,13,14:

• Identify and treat any other underlying cause of thrombocytopenia (stop antibiotics, treat infections, and control coagulopathy)
• Reduce chemotherapy dose, frequency or alter the chemotherapy regimen
• Platelet transfusion support can be used if maintenance of chemotherapy dose intensity is vital for response or survival, and is indicated if the patient is bleeding or to prevent major bleeding if platelet counts are less than 10 × 10⁹/L (<20 × 10⁹/L if febrile)
• Recombinant interleukin-11 (oprelvekin) is the only approved treatment for CIT; however, its use is limited by adverse effects
• TPO-RAs increase platelet production but are not approved for CIT, and their use should ideally be as part of a clinical trial; if TPO-RAs are considered, romiplostim is the preferred agent
• Antifibrinolytic agent tranexamic acid is not recommended for the prevention of haemorrhage in CIT

Febrile and non-febrile neutropenia

Dr Lyman discusses guideline-recommended management of febrile and non-febrile neutropenia following cancer treatment. View transcript

Most patients undergoing chemotherapy and radiation therapy will develop neutropenia, which is defined by the absolute neutrophil count (ANC) and categorised as moderate (ANC <1,000 cells/µL), severe (ANC <500 cells/µL) or profound (ANC <100 cells/µL)¹⁵.

Patients with neutropenia are highly susceptible to infection and require careful monitoring for fever, chills and sweats¹⁵

The most dangerous complication of neutropenia is febrile neutropenia (FN), which is defined by ESMO and NCCN guidelines as a one-time oral temperature of >38.3°C or a sustained temperature of >38°C (100.4°F) for ≥1 hour in a patient who has an ANC of <500 cells/μL^10,16. ASCO guidelines define FN as a one-time oral temperature of >38.3°C or a sustained temperature of >38°C (100.4°F) for ≥1 hour in a patient who has an ANC of <1,000 cells/μL^15,17.

FN can be effectively prevented by administering granulocyte colony-stimulating factors (G-CSFs); meta-analyses indicate that primary prophylaxis with G-CSF (filgrastim) reduces the risk of FN by at least 50%^18,19. However, G-CSF prophylaxis is recommended only for patients who are to receive a chemotherapy regimen with a high FN risk (≥20%) or who have an overall FN risk ≥20%^10,16,20. Overall FN risk is estimated for patients who receive a chemotherapy regimen with an intermediate FN risk (10–20%). For these patients, special attention is given to patient-related risk factors, such as age >65 years and the presence of serious comorbidities. G-CSF prophylaxis is not indicated if the planned chemotherapy regimen has a low FN risk (<10%) or if overall FN risk is <20%.^10,16,20.

Age ≥65 years, an Eastern Cooperative Oncology Group Score ≥2 and advanced stage (≥2) are risk factors for FN, and the level of risk is also influenced by the type of cancer, cytotoxic regimen, dose intensity, comorbidities and previous episodes of FN^10,16,17,20.

Initial management should include taking a detailed medical history, including past infections with antibiotic-resistant organisms. A full-body examination looking for infection entry points should be performed, as well as routine investigations, including^16,21:

• Urgent blood testing to assess bone marrow, renal and liver function
• Coagulation screen
• C-reactive protein
• Blood cultures, including cultures from indwelling intravenous catheters
• Urinalysis and culture
• Sputum microscopy and culture
• Stool microscopy and culture
• Skin lesion assessment (aspirate/biopsy/swab)
• Chest radiograph

The majority of FN cases can be resolved with prompt empirical therapy with tailored antibacterial therapy if the type of infection is known¹⁶. In patients at high risk of FN, treatment with intravenous broad-spectrum antibiotics is recommended^16,21. Oral antibacterial therapy can be started for patients at low risk of FN who^16,21:

• Are haemodynamically stable
• Do not have acute leukaemia or evidence of organ failure
• Do not have pneumonia, an indwelling venous catheter or severe soft tissue infection

ESMO guidelines recommend using the Multinational Association of Supportive Care in Cancer (MASCC) FN risk calculator to pre-emptively manage this condition¹⁶. A MASCC score of ≤20 indicates high risk, while a score of ≥21 indicates low risk²². ESMO guidelines state that patients identified as high risk by the MASCC criteria should be admitted to hospital and receive inpatient antibiotic therapy, whereas those at low risk may be treated with outpatient parenteral regimens¹⁶.

However, ASCO and the Infectious Diseases Society of America (IDSA) guidelines recommend using clinical judgement criteria in addition to tools such as the MASCC criteria, Talcott’s rules, or Clinical Index of Stable Febrile Neutropenia (CISNE) to decide if patients with FN require inpatient or outpatient care (Figure 1)¹⁵.

Figure 1. Algorithm for the management of febrile neutropenia in patients treated for malignancy^15,16. CISNE, Clinical Index of Stable Febrile Neutropenia; MASCC, Multinational Association of Supportive Care in Cancer.

Clinical judgement criteria that can that indicate the need for inpatient care may include accelerated hypertension, severe thrombocytopenia, inability to swallow oral medications, impaired hepatic function and an altered mental status¹⁵. Talcott’s rules classify patients into groups 1, 2, 3 or 4. Patients in groups 1–3 are considered to be at high risk and include those who were hospitalised at the time of fever onset; outpatients with an acute comorbidity requiring hospitalisation; and outpatients without comorbidities but with uncontrolled cancer. Talcott’s group 4 comprises outpatients without comorbidities and with controlled cancer, who are considered to be at low risk¹⁵.

In a pooled analysis, the MASCC score and Talcott’s rules were found to misclassify some patients as being at low risk, and serious complications developed in ≤11% of patients classified as being at low risk by the MASCC score and in 7% of patients in Talcott’s group 4¹⁵. Hence, ASCO/IDSA guidelines also recommended use of the CISNE tool, which has demonstrated better performance characteristics than the MASCC criteria and Talcott’s rules, and can improve classification of patients with solid tumours. The CISNE tool considers six variables integrated into a score that deems a score of 0 as low risk, a score of 1–2 points as intermediate risk, and a score of ≥3 as high risk. Patients with a CISNE score of ≥3 are candidates for inpatient management¹⁵.

The use of antimicrobials to prevent FN is discouraged by ESMO, but is recommended by ASCO/IDSA for patients at high risk of infection, such as patients expected to have profound, protracted neutropenia (<100 neutrophils/µL  for >7 days)^16,17.

Monotherapy and combination therapy have equivalent efficacy; however, patients at high risk of FN may benefit more from a β-lactam antibiotic in combination with an aminoglycoside^15,16. Clinical assessment and follow-up may be required every 2–4 hours in severe cases, while daily assessment of fever trends, bone marrow and renal function is recommended until the patient is afebrile for at least 24 hours¹⁶.

Nausea and vomiting

Dr Lyman highlights guideline-recommended management strategies for nausea and vomiting caused by cancer treatments. View transcript.

The risk of chemotherapy-induced nausea and vomiting (CINV) for each patient should be ascertained on the basis of emetogenic potential of the treatment (Table 1 and Table 2) and predisposing factors, such as gender, type of cancer and age. A useful tool recommended by the MASCC and ESMO for predicting CINV risk can be found at www.riskcinv.com.

Table 1. Emetogenic risk of intravenous anticancer treatments^23,24.

Table 2. Emetogenic risk of oral anticancer treatments²³.

Management of CINV depends on the emetogenic potential of the anticancer therapy that a patient is taking (high risk: emesis documented in >90% of patients; moderate risk: emesis documented in 30–90% of patients; low risk: emesis documented in 10–30% of patients; minimal risk: emesis documented in <10% of patients)^23-25.

High emetic risk

European and US guidelines recommend a four-drug combination of a neurokinin-1 (NK1) receptor antagonist, a 5-hydroxytryptamine 3 (5-HT₃) receptor antagonist (ondansetron, granisetron), dexamethasone and olanzapine on day 1 of treatment to prevent acute nausea and vomiting. Dexamethasone and olanzapine should be continued on days 2–4 to prevent delayed nausea and vomiting in patients on anthracycline/cyclophosphamide (AC) chemotherapy^24,25. For patients on non-AC chemotherapy, olanzapine should be continued on days 2–4 to prevent delayed nausea and vomiting^24,25.

For high-emetic-risk total body radiation therapy, prophylaxis with a two-drug combination of a 5-HT₃ receptor antagonist and dexamethasone is recommended^24,25

Moderate emetic risk

Adults treated with carboplatin-based moderate-emetic-risk treatments should be offered a three-drug regimen of a 5-HT₃ receptor antagonist, dexamethasone and an NK1 receptor antagonist before treatment to prevent acute nausea and vomiting^24,25. For oxaliplatin-based or other non-carboplatin-based moderate-emetic-risk treatments, patients should be offered a two-drug combination of a 5-HT₃ receptor antagonist (preferably palonosetron) and dexamethasone before treatment. An NK1 receptor antagonist may be added to the regimen for women ≤50 years of age receiving oxaliplatin-based chemotherapy^24,25. ASCO further states that patients treated with cyclophosphamide, doxorubicin, oxaliplatin and other moderate-emetic-risk drugs known to cause delayed CINV may be offered dexamethasone on days 2–3²⁵.

Patients receiving upper abdomen/craniospinal moderate-emetic-risk radiation therapy should be offered prophylaxis with a 5-HT₃ receptor antagonist with optional dexamethasone^24,25.

Low and minimal emetic risk

European and US guidelines recommend that patients treated with low-emetic-risk agents may be offered a single antiemetic agent, such as a 5-HT₃ receptor antagonist or dexamethasone, before treatment for the prevention of acute nausea and vomiting^24,25. European guidelines also suggest a dopamine receptor antagonist, such as metoclopramide, as an option²⁴. Patients should not be routinely offered an antiemetic agent prior to receiving minimal-risk emetic treatments^24,25. Patients should also not be routinely offered an antiemetic for the prevention of delayed nausea and vomiting following low or minimal-emetic-risk treatments²⁴.

Patients undergoing low-emetic-risk radiation therapy to the brain can be offered rescue dexamethasone therapy^24,25. Patients who are treated with low-emetic-risk radiation therapy to the head and neck, thorax or pelvis, or minimal-risk radiation therapy to the extremities or breast can be offered rescue therapy with either dexamethasone, a 5-HT₃ receptor antagonist, or a dopamine-receptor antagonist^24,25.

Mucositis

Oral and gastrointestinal (GI) mucositis caused by high-dose chemotherapy and/or radiation continues to be an important clinical problem. The ESMO 2015 guidelines recommend the following for the prevention and treatment of oral mucositis²⁶:

• 30 minutes of oral cryotherapy to prevent oral mucositis in patients receiving bolus 5-fluorouracil chemotherapy
• Recombinant human keratinocyte growth factor-1 (KGF-1/palifermin) to prevent oral mucositis in patients receiving high-dose chemotherapy and total body irradiation followed by haematopoietic stem cell transplantation
• Low-level laser therapy to prevent oral mucositis in patients receiving haematopoietic stem cell transplantation conditioned with high-dose chemotherapy, with or without total body irradiation
• Patient-controlled analgesia with morphine to treat pain due to oral mucositis
• Benzydamine mouthwash to prevent oral mucositis in patients with head and neck cancer receiving moderate-dose radiation therapy (up to 50 Gy) without concomitant chemotherapy

The MASCC and International Society of Oral Oncology (ISOO) support these recommendations and additionally recommend low-level laser therapy for the prevention of oral mucositis in adults receiving radiation therapy to the head and neck, with or without chemotherapy²⁷. For patients undergoing haematopoietic stem cell transplantation, oral cryotherapy is recommended when conditioning includes high-dose melphalan, and KGF-1 is recommended when conditioning includes high-dose chemotherapy and total body irradiation²⁷.

The ESMO 2015 guideline recommendations for the prevention and treatment of GI mucositis include²⁶:

• The use of intravenous amifostine in patients receiving radiation therapy to prevent radiation proctitis
• Subcutaneous octreotide twice daily to treat diarrhoea secondary to mucositis induced by standard- or high-dose chemotherapy if loperamide is ineffective  

Diarrhoea

Diarrhoea is a common side effect of various antineoplastic treatments and can be classified as uncomplicated or complicated²⁸.

To ascertain the severity of diarrhoea, it should first be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE)²⁹

Uncomplicated diarrhoea

Grade 1 or 2 diarrhoea with no other complications may be classified as ‘uncomplicated’ and managed conservatively with oral hydration and loperamide (4 mg to start and then 2 mg every 4 hours or after each loose stool)²⁸. Skin barrier creams should be used to prevent skin irritation caused by increased faecal contact²⁸.

Complicated diarrhoea

Patients with complicated diarrhoea, which includes mild-to-moderate diarrhoea accompanied by moderate-to-severe cramping, nausea and vomiting, cognitive decline, fever, sepsis, neutropenia, bleeding or dehydration, require hospitalisation for closer monitoring and evaluation²⁸.

Complicated diarrhoea is managed with intravenous rehydration fluids, antibiotics and subcutaneous octreotide at a starting dose of 100–150 µg three times a day. If the patient is severely dehydrated, octreotide can be administered intravenously at a dose of 25–50 µg/h. The dose can be rapidly escalated up to 500 µg subcutaneously until the diarrhoea is controlled. Additional evaluations to be performed include a complete blood count, electrolyte profile and a stool workup investigating the presence of blood, Clostridium difficile, Salmonella, Escherichia coli, Campylobacter and infectious colitis²⁸.

Constipation

Best practice for management of constipation is a balance between prevention, self-care, and oral and rectal laxative therapy. Self-care strategies include increasing fluids, dietary fibre intake and mobility³⁰.

Other classes of laxatives, including bulk-forming laxatives, detergent/stool softener and liquid paraffin, are generally not recommended over osmotic and stimulant laxatives, especially in cases of advanced cancer³⁰.

Suppositories and enemas are the recommended first-line therapy where there is faecal impaction and/or where oral laxatives have failed to relieve constipation³⁰.

Acute radiation dermatitis

A standardised approach to management of acute radiation dermatitis (ARD) has been limited by the lack of high-quality evidence. To address this gap, in January 2023, MASCC conducted a systematic review of current evidence on interventions for the prevention and treatment of ARD³¹. This review included 235 studies, of which 149 were randomised controlled clinical trials; however, definitive recommendations could not be made on the basis of published evidence as there was considerable variability and insufficient high-quality evidence. A four-round Delphi consensus process was therefore undertaken to generate recommendations based on the opinions of 42 international ARD experts. Interventions were recommended if at least 75% consensus was reached³².

The Delphi consensus process recommended six interventions for the prevention of ARD, including photobiomodulation therapy and silicone film (in people with breast cancer), polyurethane film, mometasone furoate, betamethasone and olive oil. For the management of ARD, foam dressings were recommended (Table 3)³².

The study concluded that most interventions could not be recommended because there was insufficient evidence, conflicting evidence, or lack of consensus to support use³². This suggests the need for further research on the prevention and management of ARD. However, clinicians can consider implementing the recommended interventions in their practice until additional evidence becomes available.

Table 3. Delphi consensus recommendations for interventions to prevent or manage acute radiation dermatitis³². Note, recommended interventions are those with a consensus of ≥75%. Interventions with consensus of <75% could not be recommended.

Managing side effects associated with targeted therapies

Advances in our understanding of the mechanisms underlying cancer development have created the opportunity for new therapeutic approaches, termed ‘targeted therapies’, that selectively interfere with molecules or pathways involved in tumour growth and progression³³.

Many targeted therapies work through inactivation of growth factors and their receptors that control specific functions in cancer cells³³. Small-molecule inhibitors and monoclonal antibodies are the two major approaches of targeted therapy. Monoclonal antibodies target specific antigens on the extracellular surface (Figure 2), while small molecules penetrate the cell membrane to interact with intracellular proteins and enzymes (Table 4)³⁴.

Figure 2. Monoclonal antibodies used in various cancers³⁵. ADCC, antibody-dependent cellular cytotoxicity; APC, antigen-presenting cell; CAR-T, chimeric antigen receptor T cell; CD, cluster of differentiation; CDC, complement-dependent cytotoxicity; CTLA-4, cytotoxic T-lymphocyte associated protein 4; Fc, fragment crystallisable; HER2, human epidermal growth factor receptor 2; mAb, monoclonal antibody; MHC, major histocompatibility complex; NK, natural killer; PD-L1, programmed death-ligand 1; scFv, single-chain variable fragment; TCR, T cell receptor; VEGF, vascular endothelial growth factor.

Table 4. Small-molecule inhibitors used in various cancers^34,36.

Targeted therapies have fewer reported toxicities and better tolerance when compared with chemotherapy^37,38. However, many targeted drugs require an extended or indefinite treatment period, which can cause long-term side effects that can be distressing for many patients. Although the incidence of side effects is lower because of target specificity, adverse effects, such as hypertension, and dermatological toxicities due to off-target drug effects are frequently observed ^33,37-39.

Management of hypertension

Management of hypertension involves antihypertensive therapy, aiming to achieve a blood pressure (BP) of <130/80 mmHg³⁹. Discontinuation of treatment is recommended if systolic BP is >180 mmHg or diastolic BP >110 mmHg^39,40. First-line antihypertensive agents include angiotensin receptor blockers or angiotensin-converting enzyme (ACE) inhibitors, dihydropyridine calcium channel blockers, or thiazide or thiazide-like diuretics³⁹. b-blockers should be reserved for individuals with a specific indication for their use, or those who did not achieve treatment success with, or have contraindications to, first-line antihypertensive agents³⁹.

Management of dermatological side effects

Accurate grading is a critical component to determine the appropriate intervention and management response.

The most widely used grading system is the Common Terminology Criteria for Adverse Events (CTCAE), which takes into consideration the degree to which activities of daily living may be affected^37,41

In CTCAE, an adverse event is defined as any abnormal clinical finding temporally associated with the use of a cancer therapy. These criteria are used for the management of treatment administration and dosing, and to provide standardisation and consistency in the definition of treatment-related toxicity^37,41.

Maculopapular rash (morbilliform eruption)

Recommended treatment⁴¹:

• Topical or oral corticosteroids
• Antihistamines
• Careful monitoring to prevent progression to Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN)

Papulopustular (acneiform) rash

Recommended treatment includes topical corticosteroids and an oral tetracycline antibiotic (doxycycline 100 mg two times a day, minocycline 50 mg two times a day, or oxytetracycline 500 mg two times a day) for at least 6 weeks. For more severe cases, a short course of systemic corticosteroids (e.g., prednisone 0.5–1 mg/kg body weight for 7 days with a weaning dose over 4–6 weeks) can be considered³⁷.

Xerosis

Management is done conservatively by educating the patient to minimise showering, use tepid water and avoid soaps^37,38. If eczema is present, a 1–2-week course of corticosteroids is recommended. To decrease pruritis, oral antihistamines gabapentin and pregabalin can be used³⁷.

Hand–foot skin reaction

Patient education on the signs and symptoms of hand–foot skin reaction is a vital part of prevention³⁷. Certain lifestyle modifications, including avoiding vigorous exercise, hot water and tight-fitting clothing, should be communicated. To alleviate the symptoms of hand–foot skin reaction, emollients and moisturising creams can be used³⁷.

Stevens–Johnson syndrome / toxic epidermal necrolysis

Management of SJS/TEN using intravenous immunoglobulin (IVIg) is recommended⁴¹. For SJS, a total dose of 2 g/kg IVIg is often considered⁴¹. IVIg should be administered as soon as possible after confirming the diagnosis of TEN at a recommended total dose of 3 g/kg⁴¹.

Management of immune thrombocytopenia

Severity of immune thrombocytopenia induced by immunotherapy is graded according to platelet count, with management based on the grade of thrombocytopenia (Table 6)⁴⁷.

Table 6. Incidence and management of immune thrombocytopenia according to grade of severity^47,48. Proportion of treated patients affected based on patients with cancer (N=1,038) treated with immune checkpoint inhibitors. IVIg, intravenous immunoglobulin.

Management of cardiovascular side effects

A range of cardiovascular (CV) side effects have been reported after treatment with immunotherapy, including myocarditis, pericarditis, arrhythmias, cardiomyopathy, and vasculitis^49,50.

Cardiovascular complications have been reported with all immune checkpoint inhibitors and, although rare, are associated with high mortality rates^47,51

For patients who develop new CV symptoms after onset of treatment, a full workup should be conducted and may include⁴⁷:

• Electrocardiogram
• Troponin and creatine phosphokinase
• B-type natriuretic peptide (BNP)
• Echocardiogram
• Chest X-ray
• Stress test
• Cardiac catheterisation
• Cardiac magnetic resonance imaging

If myocarditis, pericarditis, arrhythmias, impaired ventricular function with heart failure, or vasculitis is suspected, therapy should be withheld⁴⁷. For symptomatic patients, high-dose corticosteroids (prednisone 1–2 mg/kg per day) should be initiated. In patients without an immediate response to high-dose corticosteroids, consider methylprednisolone 1 g/day and either mycophenolate, infliximab, or antithymocyte globulin^50,51. Abatacept or alemtuzumab as additional immunosuppression should be considered in life-threatening cases⁴⁷.

Management of endocrine side effects

The most common endocrine side effects associated with immunotherapy include hypothyroidism and adrenal insufficiency^43,47.

Hypothyroidism

Hypothyroidism is more common than hyperthyroidism and can be detected by routine blood tests for thyroid-stimulating hormone (TSH) and free thyroxine (FT4)^43,47. Once detected, routine monitoring should be done at baseline and before every infusion for 4–6 weeks while receiving treatment. Thyroid hormone supplementation can be initiated for TSH levels above 10 mIU/L⁴⁷.

Adrenal insufficiency

Adrenal insufficiency is associated with inhibitors of the immune checkpoint programmed cell death protein 1 (PD-1) and its ligand PD-L1⁴³. Management depends on the clinical severity. Patients with mild signs and symptoms can be started on hydrocortisone (up to 30 mg daily); those with moderate symptoms should receive hydrocortisone 30–50 mg daily or prednisone 20 mg daily^47,50. Fludrocortisone (0.05–1 mg daily) may also be required for mild or moderate symptoms⁴⁷.

Patients with suspected adrenal crisis should receive an immediate dose of up to 100 mg intravenous hydrocortisone plus fluid resuscitation with 2 L saline⁴⁷

Once clinically stable, maintenance oral therapy should be continued as previously described.

Management of diarrhoea

Diarrhoea can occur in up to 54% of patients treated with anti-CTLA-1 antibodies, or anti-CTLA-4 antibody and PD-1 combinations⁴⁷. Management of diarrhoea depends on severity, but in moderate and severe cases treatment should be temporarily withheld until symptoms resolve^47,50. Corticosteroids (1–2 mg/kg/day prednisone or equivalent) should be administered in moderate cases if diarrhoea persists, and in severe cases^47,50.

Patient activation for managing cancer treatment toxicities

Patient activation, defined as an individual's knowledge, skill and confidence in managing their own health, has gained recognition for its positive impact on outcomes in individuals undergoing cancer treatment⁵². Research supports the notion that more activated patients monitor their conditions more closely, exhibit greater adherence to treatments, and show increased acceptance of recommended care, resulting in improved clinical outcomes. While this evidence spans different patient populations and various settings, studies focusing specifically on patient activation in patients with cancer are limited⁵².

With minimal clinical guidance, cancer patients and their families bear increasing responsibility for day-to-day management, encompassing symptom control, adherence to complex treatment regimens, and the adoption of behaviours that reduce the risk of disease recurrence⁵³. As cancer survivorship increases, the need for long-term self-management by patients becomes crucial.

To address this gap, a pilot randomised trial was undertaken in 2023 to evaluate the feasibility, acceptability and preliminary effectiveness of SMARTCare (Self-Management and Activation to Reduce Treatment Toxicities), an intervention comprising an online self-management education programme (I-Can Manage) and five sessions of nurse-delivered telephone coaching, designed to improve patient activation⁵³. Patients starting systemic therapy for lymphoma or colorectal or lung cancer at three centres in Ontario, Canada, were recruited to the study and randomised to the intervention group (SMARTCare) or an enhanced education control group⁵³.

In this pilot study, patient-reported outcomes were evaluated using measures such as patient activation, symptom distress, self-efficacy and quality of life⁵³. Data were collected at baseline and at multiple time points. Out of 90 approached patients, 62 (68.9%) participated, with an average age of 60.5 years. Most were married (77.1%), university educated (71%), had colorectal cancer (41.9%) or lymphoma (42.0%), and had advanced disease (75.8%). Attrition was higher in the intervention group (36.7% vs 25% in control). Adherence to the intervention was low, but the intervention group showed improvements in patient activation scores⁵³.

The study concluded that early self-management education and coaching may enhance patient activation during cancer treatment. However, due to low adherence and attrition, a larger trial is needed to assess the feasibility and effectiveness of the intervention⁵³.