Mucositis​ = Painful inflammation and ❌ of the mucous membranes lining the digestive tract (especially ❌)​. ❌% of all CT patients will experience mucositis. It can lead to infections, ❌ disorders, severe pain, compromised airway, tissue necrosis, and significant ❌​.
Usually begins to manifest 5-7 days after CT (typically ❌)​.
Risk factors include:​
- High-dose CT with alkylating agents (eg ❌) or topoisomerase II inhibitors​ (eg ❌)
- Pre-existing oral lesions/infections, poor dental ❌/dentures​
- ❌ ethnicity
- ❌ malnutrition​

Mucositis prevention​:
Remove risk factors (e.g. ❌ therapy)​
Drink adequate ❌​
Cryotherapy (❌ before bolus CT; not oxaliplatin)​
❌ mouth rinse

Treatment​
Routine mouth care​
Analgesia (topical ❌, topical morphine, oral morphine if ❌)​
❌
Saliva substitutes ​

Diarrhoea:
Caused by direct toxicity to the ❌ cells leading to inflammation with ❌ release .
Most common with ❌ EGFR inhibitors.
Tx:
❌ orally, then ❌ until diarrhoea free​
❌ – for patients not responding to loperamide ​
NOTE Anti-diarrhoeals should ❌ be used in patients with suspected ❌​ and do not forget importance of ❌

Constipation​:
Affects 50-70% of patients on chemotherapy​
Can lead to anorexia, nausea, vomiting, abdominal pain, bowel ❌
Risk medications: ❌ (ondansetron)​
Treatment: Stool softener, stimulants, fleet enema, manual or surgical evacuation, hydration ​

Hypersensitivity reactions​ can cause acute ❌, pruritic ❌, fever, nausea/vomiting, rigors, flushing, ❌cardia, ❌tension, angioedema. These are severe in <❌ of patients.
Causes:
Taxanes - ❌ exposure, ❌ onset, premedicate with ❌
❌ (first dose requires test dose, IM less frequent)​
Monocolonal antibodies (pre-medicate with ❌)​ - If severe, stop or interrupt infusion and give fluids and ❌​.

Alopecia​
- occurs 1-2 ❌ post-chemotherapy ​
- reversible (1-2 ❌ after cessation of therapy)​
- ❌ 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: ❌ liposomal ❌, high dose cytarabine ​
Treatment: drug cessation and symptomatic treatment (❌ emollient, analgesia, ❌ compress, topical ❌

Extravasation​
With an irritant drug: ❌-term injury. No necrosis. May induce ❌ inflammatory reaction. Blood ❌ remains intact​.
With a vesicant drug: Hardening, burning, can lead to tissue ❌​. DNA binding or DNA non-binding​. DNA ❌ may affect underlying ligaments, nerves, and bone​.

❌ (vesicant) cause the most severe extravasation​.

Treatment​:
Stop ❌, Leave ❌ access, Aspirate, Plan​
Anthracyclines: ❌ compresses​
Vinca alkaloids: ❌ compresses​
Antidotes: Dexrazoxane or ❌ topical solution for anthracycline extravasation; ❌ for vinka alkaloids​

Tumour Lysis syndrome​: lysis of large numbers of cancer cells​.

Metabolic abnormalities: hyperuricaemia, hyperkalaemia, hyperphosphataemia, secondary hypocalcaemia and uraemia​ (increased ❌, decreased ❌)

Symptoms: nausea and ❌, diarrhoea, anorexia, lethargy, oedema, fluid overload, ❌ heart failure, haematuria, cardiac ❌, seizures, muscle cramps, tetany, syncope.​

More common on the ❌ cycle of treatment. ​

Risk factors: high tumour cell proliferation ❌, bulky disease (greater than ❌ cm), chemosensitive malignancies*, high intensity or highly ❌ therapy, novel or targeted therapy.​

*Malignancies associated with a higher risk: ❌ lymphoma, Burkitt's lymphoma, ❌ lymphoblastic leukaemia and acute myeloid ❌, and occasionally those with solid tumours. ​

Additional risk factors: ❌ insufficiency or renal failure, dehydration, decreased ❌ flow, pre-existing uraemia or hyperuricaemia, pre-existing hyperphosphataemia.​

Prophylaxis in intermediate or high risk​: Vigorous ❌ hydration​, ❌, ❌​ (n those who do not adequately&nbsp;respond to hydration and allopurinol)

Ocular toxicity​
- with ❌-HiDAC​
- excessive tearing, pain, photophobia, presence of foreign body, ​
- prevention: ❌ tears, ❌ corticosteroids​
Treatment: ❌ cytarabine and administer topical corticosteroids​

​
Otological toxicity ​
- w/ ❌​
- Damage to ❌
- ❌ side effect ​
- When detected, replace with ❌ if appropriate​
- ❌ auditory function​

Nephrotoxicity​
- w/ ❌​
- Dose ❌
- Risk with ❌ doses, ❌ exposure, pre-existing ❌ damage, use of other nephrotoxic agents​
- ❌% incidence​
- Manifests as increases in ❌, decreased ❌ output, ❌kalemia, hypomagnesemia, hyponatremia ​
- Prevention: ❌ doses, sub with ❌, aggressive ❌, magnesium, ?mannitol​
- Monitor: ❌ balance, weight, assess for signs/symptoms of fluid overload​
- Treatment: ❌ cisplatin, replenish electrolytes – revising ARF in 310​

Types of Nausea/Vomiting​
Acute (up to 24h after CT; peak ❌ hours)​
Delayed (starts ❌ after CT to ❌ days)​
Anticipatory (begins as next ❌ becomes closer)​
Breakthrough (happens despite ❌)​
Refractory (prevention/treatment does ❌ work)​

If not managed appropriately:​
Serious ❌ imbalance, de❌, anorexia​
Deterioration in physical and mental status, ❌ withdrawal​

Classiciation of treatment emetogenic risk: ​
Minimal (<10%)​
Low (10-30%) [❌]​
Moderate (30-90%) [❌]​
High (>90%) [❌]​

Optimal emetic control in the ❌ phase (the first 24 hours) is essential to ❌ nausea and vomiting in the ❌ phase (24 to 72 hours post chemotherapy).​

Drug: Aprepitant ​
Class: ❌ receptor ❌​
Indicated for prevention of N/V in ❌ emetogenic chemotherapy. ❌ inhibitor. Always used in ❌.

Prophylaxis and Treatment​:
- High emetogenic potential​: use ❌ + ❌ (q12h) + ❌ ​
- Moderate emetogenic potential​: ❌ + Dexamethasone ❌
- Low emetogenic potential​: ❌ dose or ❌
- Minimal emetogenic potential​: None but can use as needed (dexamethasone or ​ metoclopramide or prochlorperazine)​

Anaemia in cancer can be caused by a number of different mechanisms:​

The cancer​:
- Cancer ❌ 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 ❌ ​
- Triggered immune response with the release of various ❌ that interfere with bone marrow function and ❌ red cell survival​
- Cancer cells release cytokines that can lead to iron ❌, reducing the production of red blood cells (RBCs)​

The treatment​
- Chemotherapy agents target rapidly dividing cells​

Terminologies:
Ferritin – amount of iron ❌ in body (iron storage ❌ that keeps iron in a soluble and non-toxic form)​

Transferrin or total iron ❌ capacity - a measure of the ❌ amount of iron the blood can carry​

Haemoglobin – oxygen carrying structures ​

Haematocrit – volume % of ❌ cells in blood​

Mean Corpuscular Volume/Mean Cell Volume (MCV) – ‘❌’ of red blood cells ​

Reticulocyte count - measure the level of reticulocytes in your blood​

The MCV is used to categorise anaemia.
Microcytic anaemia – MCV < ❌
Normocytic anaemia – MCV ❌​
Macrocytic anaemia – MCV > ❌

(Some references define macrocytic anaemia as > 100 fL.)​

​

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

Normal MCV – Normocytic anaemia​:
High reticulocyte count suggests ❌ blood loss – acute blood loss, haemolysis​. Low reticulocyte count suggests body is unable to ❌ RBCs at a healthy rate​.
Low WBCs and platelets – ❌
Normal or high WBCs/platelets – ❌ conditions (progress to microcytic as disease progresses), ❌​
- Treatment:​ Transfusion, ❌-stimulating agents ​

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

Erythropoiesis-stimulating agents:
1. Epoetin alfa (recombinant ❌ erythropoietin)​
- Stimulate erythropoiesis by binding to ❌, stimulating differentiation and proliferation​
- Stimulate release of ❌ from bone marrow​
- Increase synthesis of cellular ❌ – need adequate iron stores​
- Contraindicated: uncontrolled ❌, unable to receive thromboprophylaxis​
- Adverse effects: hypertension, GI ❌, headache, influenza symptoms, very rarely cause ❌

Low MCV - Microcytic Anaemia​:
Cell size is decreased due to reduced ❌; either less haem (i.e. iron) or an imbalance in ❌ synthesis (in genetic disorders which alter globin production)​

The main causes:​
- Low ferritin​ = ❌ deficiency (blood loss, dietary deficiency, occasionally malabsorption)
- Normal or high ferritin​ =
TIBC low: Anaemia of ❌ disease (also associated with normocytic anaemia)​
OR TIBC normal or high: ❌ (e.g. thalassaemia), lead intoxication, sideroblastic anaemias (rare ❌ or acquired disorders)​

- In a primary care setting in New Zealand, ❌ will be the most likely causes of microcytic anaemia.​

Patient education points for iron salts:​
More effective if taken on ❌ stomach​
Can take with food if causes stomach upset​
May discolor stools (❌)​
Do not take with ❌
May need to space from certain medications​
Vitamin C (orange juice) may increase iron absorption (myth?)​
❌ common​

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

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

Types of cancer pain:
- Acute vs. chronic pain​
​
- Nerve pain – ❌ on nerves or spinal cord (i.e. neuropathic)​
- Bone pain – ❌ to bone tissue (e.g. metastases)​
- Soft tissue or visceral pain – ❌ (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 ❌

WHO Cancer Pain Ladder​:
Step 1 = ❌ ​ +/- adjuvant
Step 2 = Opioid for ❌ +/- non-opioid +/- adjuvant​
Step 3 = Opioid for ❌ +/- non-opioid +/- adjuvant​

❌​ - mild, mod
❌ - mod, strong

Adjuvants:​
❌ medications​
❌​
Topical medications​

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

People with cancer in the bone have abnormally high levels of ❌, causing fractures, bone pain​, osteoporosis​, and hypercalcaemia.

❌ (zoledronate or pamidronate) reduce ❌ of osteoclasts – strengthen bone, reduce pain, treat hypercalcaemia​.

Side effects include ❌ symptoms, which usually subside within ❌ hours of the infusion (treat with paracetamol).

Nephrotoxicity risk: adequate ❌ can enhance renal protection., may be contraindicated in ❌ failure.

Severe pain may require rapid escalation of parenteral opioid therapy until pain is partially relieved.
Moderate pain: total daily dose (TTD) increased ❌% OR add the amount taken ❌ the previous day​
Reducing by 25-50% in patients who have pain control but experiencing ❌ 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 ❌ of short-acting opioid so pain is well controlled​. First dose of the modified-release preparation is given ❌ 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 ❌ of morphine equivalents​
2. Decrease by ❌
3. Split into required ❌ of long-acting doses​

Example: TTD = 130mg morphine x ❌ = 97.5mg
/ 2 doses = 50mg every 12 hours long-acting product ​

Fentanyl patches:
- Less ❌ compared to morphine. It is favourable in the presence of ❌ impairment ​
- Starting doses of ❌ first option for moderate to severe pain
- Usually dosed every ❌ 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 ❌ 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 ❌ administration​
- Release ❌% of drug within 1 hour for most patients and the remaining ❌% of drug by controlled-release​
- The immediate-release and modified-release formulations have ❌! care.
- Usually reserved for patients in whom ❌ is not effective at optimal doses, not tolerated, or if morphine is contra-indicated​

Methadone
- Well tolerated in ❌ renal impairment. May be effective when there is ❌ pain because of its ❌ receptor activity.​
- Long and widely variable ❌
- Less associated ❌ ​
- Oral dosing is usually ❌ initially with ❌ dose increases (due to its long half-life and risk of accumulation)​

Drowsiness and ❌ 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​:
- ❌ of total daily dose (TTD)
- can be given ❌ an activity that causes ❌ break-through pain such as a wound dressing
- subcut or IV if swallowing is an issue