ON15,16,17 Supportive care

Mucositis​ = Painful inflammation and [blank_start]ulceration[blank_end] of the mucous membranes lining the digestive tract (especially [blank_start]mouth and throat[blank_end])​. [blank_start]40-75[blank_end]% of all CT patients will experience mucositis. It can lead to infections, [blank_start]nutritional[blank_end] disorders, severe pain, compromised airway, tissue necrosis, and significant [blank_start]bleeding[blank_end]​. Usually begins to manifest 5-7 days after CT (typically [blank_start]2-3 weeks[blank_end])​. Risk factors include:​ - High-dose CT with alkylating agents (eg [blank_start]cyclophosphamide[blank_end]) or topoisomerase II inhibitors​ (eg [blank_start]doxorubicin[blank_end]) - Pre-existing oral lesions/infections, poor dental [blank_start]hygiene[blank_end]/dentures​ - [blank_start]White[blank_end] ethnicity - [blank_start]Smoking, alcohol consumption,[blank_end] malnutrition​

Mucositis prevention​: Remove risk factors (e.g. [blank_start]dental[blank_end] therapy)​ Drink adequate [blank_start]water[blank_end]​ Cryotherapy ([blank_start]ice chips swishing for 30 min[blank_end] before bolus CT; not oxaliplatin)​ [blank_start]Saline and bicarbonate[blank_end] mouth rinse Treatment​ Routine mouth care​ Analgesia (topical [blank_start]lidocaine[blank_end], topical morphine, oral morphine if [blank_start]severe[blank_end])​ [blank_start]Magic mouth wash ​[blank_end] Saliva substitutes ​

Diarrhoea: Caused by direct toxicity to the [blank_start]epithelial[blank_end] cells leading to inflammation with [blank_start]prostaglandin[blank_end] release . Most common with [blank_start]5-FU, capecitabine, irinotecan,[blank_end] EGFR inhibitors. Tx: [blank_start]Loperamide 4mg[blank_end] orally, then [blank_start]2mg every 2 hours[blank_end] until diarrhoea free​ [blank_start]Octreotide[blank_end] – for patients not responding to loperamide ​ NOTE Anti-diarrhoeals should [blank_start]not[blank_end] be used in patients with suspected [blank_start]C. Diff[blank_end]​ and do not forget importance of [blank_start]diet and hydration​[blank_end] Constipation​: Affects 50-70% of patients on chemotherapy​ Can lead to anorexia, nausea, vomiting, abdominal pain, bowel [blank_start]obstruction and perforation ​[blank_end] Risk medications: [blank_start]Vinca alkaloids, opioids, antiemetics[blank_end] (ondansetron)​ Treatment: Stool softener, stimulants, fleet enema, manual or surgical evacuation, hydration ​

Hypersensitivity reactions​ can cause acute [blank_start]dyspnoea[blank_end], pruritic [blank_start]rash[blank_end], fever, nausea/vomiting, rigors, flushing, [blank_start]brady[blank_end]cardia, [blank_start]hypo[blank_end]tension, angioedema. These are severe in <[blank_start]5%[blank_end] of patients. Causes: Taxanes - [blank_start]2nd/3rd[blank_end] exposure, [blank_start]fast[blank_end] onset, premedicate with [blank_start]H1 and H2 antagonists and steroids[blank_end] [blank_start]L-asparaginase[blank_end] (first dose requires test dose, IM less frequent)​ Monocolonal antibodies (pre-medicate with [blank_start]paracetamol, antihistamines and steroids[blank_end])​ - If severe, stop or interrupt infusion and give fluids and [blank_start]adrenaline[blank_end]​.

Photosensitivity ​is a dermotological toxicity causes by some medicines. Wear sunscreen, cover up, avoid sunbeds​. Which medicines can cause this?

Alopecia​ - occurs 1-2 [blank_start]weeks[blank_end] post-chemotherapy ​ - reversible (1-2 [blank_start]months[blank_end] after cessation of therapy)​ - [blank_start]taxanes[blank_end] cause total body alopecia (axillary and pubic hair, eyebrows and eye lashes)​

Hand-Foot Syndrome (palmer-plantar/acral erythema)​: - Tender erythematous skin on palms of hands and sometimes soles of feet​ - Causes: [blank_start]5-FU, capecitabine,[blank_end] liposomal [blank_start]doxorubicin[blank_end], high dose cytarabine ​ Treatment: drug cessation and symptomatic treatment ([blank_start]10% urea[blank_end] emollient, analgesia, [blank_start]cold[blank_end] compress, topical [blank_start]corticosteroids[blank_end]

Extravasation​ With an irritant drug: [blank_start]Short[blank_end]-term injury. No necrosis. May induce [blank_start]local[blank_end] inflammatory reaction. Blood [blank_start]return[blank_end] remains intact​. With a vesicant drug: Hardening, burning, can lead to tissue [blank_start]necrosis[blank_end]​. DNA binding or DNA non-binding​. DNA [blank_start]binding[blank_end] may affect underlying ligaments, nerves, and bone​. [blank_start]Anthracyclines[blank_end] (vesicant) cause the most severe extravasation​. Treatment​: Stop [blank_start]infusion[blank_end], Leave [blank_start]venous[blank_end] access, Aspirate, Plan​ Anthracyclines: [blank_start]cold[blank_end] compresses​ Vinca alkaloids: [blank_start]warm[blank_end] compresses​ Antidotes: Dexrazoxane or [blank_start]dimethyl sulfoxide[blank_end] topical solution for anthracycline extravasation; [blank_start]hyalurinodase[blank_end] for vinka alkaloids​

Tumour Lysis syndrome​: lysis of large numbers of cancer cells​. Metabolic abnormalities: hyperuricaemia, hyperkalaemia, hyperphosphataemia, secondary hypocalcaemia and uraemia​ (increased [blank_start]uric acid, potassium, phosphate[blank_end], decreased [blank_start]calcium[blank_end]) Symptoms: nausea and [blank_start]vomiting[blank_end], diarrhoea, anorexia, lethargy, oedema, fluid overload, [blank_start]congestive[blank_end] heart failure, haematuria, cardiac [blank_start]dysrrhythmia[blank_end], seizures, muscle cramps, tetany, syncope.​ More common on the [blank_start]first[blank_end] cycle of treatment. ​ Risk factors: high tumour cell proliferation [blank_start]rate[blank_end], bulky disease (greater than [blank_start]10[blank_end] cm), chemosensitive malignancies*, high intensity or highly [blank_start]potent[blank_end] therapy, novel or targeted therapy.​ *Malignancies associated with a higher risk: [blank_start]Non-Hodgkin's[blank_end] lymphoma, Burkitt's lymphoma, [blank_start]acute[blank_end] lymphoblastic leukaemia and acute myeloid [blank_start]leukaemia[blank_end], and occasionally those with solid tumours. ​ Additional risk factors: [blank_start]renal[blank_end] insufficiency or renal failure, dehydration, decreased [blank_start]urinary[blank_end] flow, pre-existing uraemia or hyperuricaemia, pre-existing hyperphosphataemia.​ Prophylaxis in intermediate or high risk​: Vigorous [blank_start]IV[blank_end] hydration​, [blank_start]allopurinol[blank_end], [blank_start]rasburicase[blank_end]​ (n those who do not adequately&nbsp;respond to hydration and allopurinol)

Ocular toxicity​ - with [blank_start]Cytarabine[blank_end]-HiDAC​ - excessive tearing, pain, photophobia, presence of foreign body, ​ - prevention: [blank_start]artificial[blank_end] tears, [blank_start]topical[blank_end] corticosteroids​ Treatment: [blank_start]D/C[blank_end] cytarabine and administer topical corticosteroids​ ​ Otological toxicity ​ - w/ [blank_start]Cisplatin[blank_end]​ - Damage to [blank_start]inner ear​[blank_end] - [blank_start]Cumulative and irreversible[blank_end] side effect ​ - When detected, replace with [blank_start]carboplatin[blank_end] if appropriate​ - [blank_start]Monitor[blank_end] auditory function​

Nephrotoxicity​ - w/ [blank_start]Cisplatin[blank_end]​ - Dose [blank_start]limiting[blank_end] - Risk with [blank_start]higher[blank_end] doses, [blank_start]previous[blank_end] exposure, pre-existing [blank_start]kidney[blank_end] damage, use of other nephrotoxic agents​ - [blank_start]25-40[blank_end]% incidence​ - Manifests as increases in [blank_start]serum creatinine[blank_end], decreased [blank_start]urine[blank_end] output, [blank_start]hypo[blank_end]kalemia, hypomagnesemia, hyponatremia ​ - Prevention: [blank_start]lower[blank_end] doses, sub with [blank_start]carboplatin[blank_end], aggressive [blank_start]hydration[blank_end], magnesium, ?mannitol​ - Monitor: [blank_start]fluid[blank_end] balance, weight, assess for signs/symptoms of fluid overload​ - Treatment: [blank_start]Stop[blank_end] cisplatin, replenish electrolytes – revising ARF in 310​

Which of these is NOT a risk factor for chemo induced nausea and vomiting?

Types of Nausea/Vomiting​ Acute (up to 24h after CT; peak [blank_start]5-6[blank_end] hours)​ Delayed (starts [blank_start]>24h[blank_end] after CT to [blank_start]7[blank_end] days)​ Anticipatory (begins as next [blank_start]dose/cycle[blank_end] becomes closer)​ Breakthrough (happens despite [blank_start]treatment/prevention[blank_end])​ Refractory (prevention/treatment does [blank_start]not[blank_end] work)​ If not managed appropriately:​ Serious [blank_start]metabolic[blank_end] imbalance, de[blank_start]hydration[blank_end], anorexia​ Deterioration in physical and mental status, [blank_start]treatment[blank_end] withdrawal​

Classiciation of treatment emetogenic risk: ​ Minimal (<10%)​ Low (10-30%) [[blank_start]5-FU, capecitabine[blank_end]]​ Moderate (30-90%) [[blank_start]taxanes, doxorubicin[blank_end]]​ High (>90%) [[blank_start]cisplatin[blank_end]]​ Optimal emetic control in the [blank_start]acute[blank_end] phase (the first 24 hours) is essential to [blank_start]prevent[blank_end] nausea and vomiting in the [blank_start]delayed[blank_end] phase (24 to 72 hours post chemotherapy).​

Drug: Aprepitant ​ Class: [blank_start]Neurokinin[blank_end] receptor [blank_start]antagonist[blank_end]​ Indicated for prevention of N/V in [blank_start]high and moderate[blank_end] emetogenic chemotherapy. [blank_start]CYP3A4[blank_end] inhibitor. Always used in [blank_start]combination[blank_end].

Prophylaxis and Treatment​: - High emetogenic potential​: use [blank_start]Ondansetron (q8h)[blank_end] + [blank_start]Dexamethasone[blank_end] (q12h) + [blank_start]Aprepitant[blank_end] ​ - Moderate emetogenic potential​: [blank_start]Ondansetron (q12h)[blank_end] + Dexamethasone [blank_start](q12h) ​[blank_end] - Low emetogenic potential​: [blank_start]Ondansetron stat[blank_end] dose or [blank_start]metoclopramide before​[blank_end] - Minimal emetogenic potential​: None but can use as needed (dexamethasone or ​ metoclopramide or prochlorperazine)​

Anaemia​ is a lack of red blood cells/haemoglobin.

Which of these is NOT a cause of anaemia?

Anaemia in cancer can be caused by a number of different mechanisms:​ The cancer​: - Cancer [blank_start]competes[blank_end] with the marrow’s function and interferes with normal red blood cell production (e.g. leukaemia)​ - Cancers of the gastrointestinal system (colon and stomach cancers) or fast growing tumours may cause frequent [blank_start]bleeding[blank_end] ​ - Triggered immune response with the release of various [blank_start]cytokines[blank_end] that interfere with bone marrow function and [blank_start]shorten[blank_end] red cell survival​ - Cancer cells release cytokines that can lead to iron [blank_start]sequestration[blank_end], reducing the production of red blood cells (RBCs)​ The treatment​ - Chemotherapy agents target rapidly dividing cells​

Which of these is NOT a cancer-specific risk factor for anaemia?

Select ALL the signs of anaemia.

Terminologies: Ferritin – amount of iron [blank_start]stored[blank_end] in body (iron storage [blank_start]protein[blank_end] that keeps iron in a soluble and non-toxic form)​ Transferrin or total iron [blank_start]binding[blank_end] capacity - a measure of the [blank_start]maximum[blank_end] amount of iron the blood can carry​ Haemoglobin – oxygen carrying structures ​ Haematocrit – volume % of [blank_start]red blood[blank_end] cells in blood​ Mean Corpuscular Volume/Mean Cell Volume (MCV) – ‘[blank_start]size[blank_end]’ of red blood cells ​ Reticulocyte count - measure the level of reticulocytes in your blood​

The MCV is used to categorise anaemia. Microcytic anaemia – MCV < [blank_start]80 fL​[blank_end] Normocytic anaemia – MCV [blank_start]80 – 95 fL[blank_end]​ Macrocytic anaemia – MCV > [blank_start]95 – 100 fL​[blank_end] (Some references define macrocytic anaemia as > 100 fL.)​ ​

High MCV – Macrocytic Anaemia​ / Megaloblastic anaemia​. - Vitamin [blank_start]B12[blank_end] (dietary or pernicious anaemia) or [blank_start]Folate[blank_end] deficiency​ - Both are required for [blank_start]DNA[blank_end] synthesis and so deficiency results in symptoms occurring in rapidly dividing tissues ([blank_start]bone marrow, GI[blank_end])​ - Usually deficiency from [blank_start]dietary[blank_end] sources (vegetarians, poor nutrition)​ - Treatment: supplementation (oral or injections if poor absorption): [blank_start]IM[blank_end] injection of vitamin B12 (hydroxocobalamin) – 1mg [blank_start]three[blank_end] times weekly x 2 weeks, then 1mg every 3 [blank_start]months[blank_end]​ Oral folic acid – [blank_start]5mg daily[blank_end] for 4 months (may then use as prophylaxis)​

Normal MCV – Normocytic anaemia​: High reticulocyte count suggests [blank_start]ongoing[blank_end] blood loss – acute blood loss, haemolysis​. Low reticulocyte count suggests body is unable to [blank_start]produce[blank_end] RBCs at a healthy rate​. Low WBCs and platelets – [blank_start]leukemia, aplastic anaemia​[blank_end] Normal or high WBCs/platelets – [blank_start]chronic[blank_end] conditions (progress to microcytic as disease progresses), [blank_start]malignancy[blank_end]​ - Treatment:​ Transfusion, [blank_start]erythropoiesis[blank_end]-stimulating agents ​

Blood transfusions​: - Raises [blank_start]haemoglobin[blank_end] quickly to improve symptoms and ensure adequate oxygen delivery ​ - Most commonly administered if haemoglobin is <[blank_start]80 g/L[blank_end]​ - Need to match blood type​​ - Risks:​ Transfusion related [blank_start]lung[blank_end] injury​ Very low risk of viral contamination (Hep B, C, HIV)​

Erythropoiesis-stimulating agents: 1. Epoetin alfa (recombinant [blank_start]human[blank_end] erythropoietin)​ - Stimulate erythropoiesis by binding to [blank_start]erythroid precursor cell receptors[blank_end], stimulating differentiation and proliferation​ - Stimulate release of [blank_start]reticulocytes[blank_end] from bone marrow​ - Increase synthesis of cellular [blank_start]haemoglobin[blank_end] – need adequate iron stores​ - Contraindicated: uncontrolled [blank_start]hypertension[blank_end], unable to receive thromboprophylaxis​ - Adverse effects: hypertension, GI [blank_start]intolerance[blank_end], headache, influenza symptoms, very rarely cause [blank_start]red cell aplasia, skin reactions ​[blank_end]

Low MCV - Microcytic Anaemia​: Cell size is decreased due to reduced [blank_start]haemoglobin[blank_end]; either less haem (i.e. iron) or an imbalance in [blank_start]globin chain[blank_end] synthesis (in genetic disorders which alter globin production)​ The main causes:​ - Low ferritin​ = [blank_start]Iron[blank_end] deficiency (blood loss, dietary deficiency, occasionally malabsorption) - Normal or high ferritin​ = TIBC low: Anaemia of [blank_start]chronic[blank_end] disease (also associated with normocytic anaemia)​ OR TIBC normal or high: [blank_start]Haemoglobinopathies[blank_end] (e.g. thalassaemia), lead intoxication, sideroblastic anaemias (rare [blank_start]genetic[blank_end] or acquired disorders)​ - In a primary care setting in New Zealand, [blank_start]iron deficiency and chronic disease[blank_end] will be the most likely causes of microcytic anaemia.​

In cancer patients, iron deficiency is usually due to nutritional deficiencies - poor oral intake, chemotherapy-induced nausea/vomiting.

Which of these is NOT an iron rich food?

What dose of elemental iron should deficient patients receive daily?

Patient education points for iron salts:​ More effective if taken on [blank_start]empty[blank_end] stomach​ Can take with food if causes stomach upset​ May discolor stools ([blank_start]dark/black[blank_end])​ Do not take with [blank_start]antacids or calcium​[blank_end] May need to space from certain medications​ Vitamin C (orange juice) may increase iron absorption (myth?)​ [blank_start]Constipation[blank_end] common​

Aplastic anaemia​: - Non-[blank_start]malignant[blank_end] condition where the bone marrow fails to produce enough blood cells​ - Exposes patients to [blank_start]anaemia[blank_end] (RBC), [blank_start]infections[blank_end] (WBC), [blank_start]bleeding[blank_end] (platelets) - Can occur at any time but usually associated with [blank_start]bone marrow[blank_end] damage​ - From: Chemotherapy, antibiotics, [blank_start]propylthiouracil, phenytoin, quinine​[blank_end] Exposure to certain chemicals such as benzene​ Radiation exposure​ Viruses​

Which of these is not an appropriate treatment for aplastic anaemia?

Cancer pain epidemiology: - Up to [blank_start]70-80[blank_end]% of patients with advanced cancer in NZ​ have pain - Patients managed by ​ oncologists (during active treatment)​, [blank_start]palliative[blank_end] services, [blank_start]hospices[blank_end], and GPs (advanced cancer)​ - Commonly the [blank_start]most[blank_end] troublesome symptom of cancer that negatively influences quality of life​ - Major [blank_start]economic[blank_end] impact by loss of productivity and caregiver burdens​ - One of the most [blank_start]difficult[blank_end] conditions to treat ​

Types of cancer pain: - Acute vs. chronic pain​ ​ - Nerve pain – [blank_start]pressure[blank_end] on nerves or spinal cord (i.e. neuropathic)​ - Bone pain – [blank_start]damage[blank_end] to bone tissue (e.g. metastases)​ - Soft tissue or visceral pain – [blank_start]body organ or muscle[blank_end] (e.g. back pain due to kidney)​ Phantom pain – pain in a body part/area that has been removed​ Referred pain – pain from an organ in the body in a [blank_start]different place ​[blank_end]

Which of thesensigns/symptoms could you observe in a sedated patient unable to communicate, that would NOT indicate pain?

WHO Cancer Pain Ladder​: Step 1 = [blank_start]Non-opioid[blank_end] ​ +/- adjuvant Step 2 = Opioid for [blank_start]mild-mod pain​​[blank_end] +/- non-opioid +/- adjuvant​ Step 3 = Opioid for [blank_start]severe pain​[blank_end] +/- non-opioid +/- adjuvant​ [blank_start]Codeine​, Dihydrocodeine[blank_end]​ - mild, mod [blank_start]Morphine​, Fentanyl​[blank_end] - mod, strong Adjuvants:​ [blank_start]Anxiety[blank_end] medications​ [blank_start]Antidepressants[blank_end]​ Topical medications​

Treating neuropathic pain: - Antidepressants, anticonvulsants​ - Start at [blank_start]low[blank_end] doses and increase as necessary to usual or maximum recommended doses ​ - Requires at least [blank_start]2 week[blank_end] trial at an adequate target [blank_start]dose[blank_end]​ - Requires continual reassessment and monitoring​ - Patient should be educated about [blank_start]INDICATION[blank_end], as may be concerned about stigma with antidepressants or anticonvulsants​ - If pain not controlled, [blank_start]opioids[blank_end] may be trialed​

People with cancer in the bone have abnormally high levels of [blank_start]osteoclasts[blank_end], causing fractures, bone pain​, osteoporosis​, and hypercalcaemia. [blank_start]Bisphosphonates[blank_end] (zoledronate or pamidronate) reduce [blank_start]activity[blank_end] of osteoclasts – strengthen bone, reduce pain, treat hypercalcaemia​. Side effects include [blank_start]headaches, nausea, and flu-like[blank_end] symptoms, which usually subside within [blank_start]48[blank_end] hours of the infusion (treat with paracetamol). Nephrotoxicity risk: adequate [blank_start]hydration[blank_end] can enhance renal protection., may be contraindicated in [blank_start]renal[blank_end] failure.

Severe pain may require rapid escalation of parenteral opioid therapy until pain is partially relieved. Moderate pain: total daily dose (TTD) increased [blank_start]25-50[blank_end]% OR add the amount taken [blank_start]as needed[blank_end] the previous day​ Reducing by 25-50% in patients who have pain control but experiencing [blank_start]adverse effects[blank_end] is also an option. Patients with cancer pain will likely need medication long-term or indefinitely​. Long-acting products are more convenient​; switch after at least [blank_start]48 hours[blank_end] of short-acting opioid so pain is well controlled​. First dose of the modified-release preparation is given [blank_start]with, or within 4 hours of[blank_end] the last dose of the immediate-release preparation, to allow time to be effective​.

To switch from regular acting to long acting:​ 1. Add up [blank_start]total daily dose[blank_end] of morphine equivalents​ 2. Decrease by [blank_start]25% ​[blank_end] 3. Split into required [blank_start]number[blank_end] of long-acting doses​ Example: TTD = 130mg morphine x [blank_start]0.75[blank_end] = 97.5mg / 2 doses = 50mg every 12 hours long-acting product ​

Fentanyl patches: - Less [blank_start]constipation[blank_end] compared to morphine. It is favourable in the presence of [blank_start]renal[blank_end] impairment ​ - Starting doses of [blank_start]12.5-25 mcg/h[blank_end] first option for moderate to severe pain - Usually dosed every [blank_start]72[blank_end] hours but can be increased to every 48 hours​ - Start low and go slow (increase dose every 48-72 hours)​ - Patient should be on regular morphine prior to patch initiation​ When initiating, put on at [blank_start]same[blank_end] time you give last dose of regular morphine​ Example: Patient receiving 60mg morphing SR – give last dose of 60mg at same time you put first patch on

Oxycodone: - Bi-phasic modified-release tablets for [blank_start]12-hourly[blank_end] administration​ - Release [blank_start]40[blank_end]% of drug within 1 hour for most patients and the remaining [blank_start]60[blank_end]% of drug by controlled-release​ - The immediate-release and modified-release formulations have [blank_start]similar sounding names[blank_end]! care. - Usually reserved for patients in whom [blank_start]morphine[blank_end] is not effective at optimal doses, not tolerated, or if morphine is contra-indicated​

Methadone - Well tolerated in [blank_start]severe[blank_end] renal impairment. May be effective when there is [blank_start]neuropathic[blank_end] pain because of its [blank_start]NMDA[blank_end] receptor activity.​ - Long and widely variable [blank_start]half-life[blank_end] - Less associated [blank_start]drowsiness, nausea, and constipation.[blank_end] ​ - Oral dosing is usually [blank_start]2.5-5 mg twice daily[blank_end] initially with [blank_start]weekly[blank_end] dose increases (due to its long half-life and risk of accumulation)​ Drowsiness and [blank_start]respiratory[blank_end] depression may develop after several days/weeks on a steady dose.​ Has place in palliative care but must be prescribed by experienced practitioner.​

Breakthrough dosing​: - [blank_start]10-15%[blank_end] of total daily dose (TTD) - can be given [blank_start]30 minutes before[blank_end] an activity that causes [blank_start]predictable[blank_end] break-through pain such as a wound dressing - subcut or IV if swallowing is an issue

Oral oxycodone is approximately 1.5–2 times more potent than oral morphine​.