Cancer Supportive Care Pharmacology

Cancer supportive care pharmacology is the use of drugs to prevent or treat the complications of cancer and its treatment: neutropenia and infection, anaemia, thrombosis, pain, bone disease, mucositis, cachexia, metabolic emergencies and cord compression. It allows full-dose treatment and protects quality of life, and applies in curative and palliative settings.

Classification. Myeloid growth factors, antimicrobials, analgesics, bone-modifying agents, anticoagulants, antiemetics, corticosteroids, rescue agents (mesna, folinic acid, dexrazoxane), appetite and symptom drugs.

• Granulocyte colony-stimulating factor: filgrastim 5 microgram/kg subcutaneously daily until neutrophil recovery (starting 24 to 72 hours after chemotherapy); pegfilgrastim 6 mg once, 24 hours or more after chemotherapy (not within 14 days before the next cycle).
• Febrile neutropenia: piperacillin-tazobactam 4.5 g intravenously every 6 hours (or cefepime 2 g every 8 hours, or meropenem 1 g every 8 hours), given within 60 minutes of presentation; add vancomycin only for catheter infection, skin infection, pneumonia or haemodynamic instability.
• Pain, step approach: paracetamol and NSAID for mild pain; oral morphine immediate-release 5 to 10 mg every 4 hours (2.5 to 5 mg in older adults and kidney impairment) for moderate to severe pain; titrate daily; breakthrough dose one sixth of the total daily dose; add a laxative (senna with macrogol) at the start.
• Neuropathic pain: amitriptyline 10 to 25 mg at night, gabapentin 300 mg at night then titrated, or duloxetine 30 to 60 mg daily.
• Bone-modifying agents: zoledronic acid 4 mg intravenously over 15 minutes every 3 to 4 weeks (reduce for creatinine clearance 30 to 60 mL/min; avoid under 30 mL/min); denosumab 120 mg subcutaneously every 4 weeks with calcium and vitamin D.
• Hypercalcaemia of malignancy: isotonic saline 3 to 4 litres in 24 hours then zoledronic acid 4 mg; calcitonin 4 to 8 IU/kg every 12 hours for the first 48 hours for symptomatic severe hypercalcaemia.
• Venous thromboembolism treatment: apixaban 10 mg twice daily for 7 days then 5 mg twice daily, or enoxaparin 1 mg/kg twice daily (or 1.5 mg/kg daily); avoid direct oral anticoagulants in gastrointestinal or genitourinary tumours at risk of bleeding.
• Spinal cord compression: dexamethasone 16 mg daily (a 10 mg intravenous loading dose is used for neurological deficit) with urgent imaging and oncological or surgical review.
• Mucositis: oral hygiene with salt and bicarbonate rinses, benzydamine mouthwash, topical analgesic, nystatin or fluconazole 100 mg daily for candidiasis; palifermin and cryotherapy for specific regimens.
• Cachexia and anorexia: dexamethasone 2 to 4 mg daily for short-term effect, megestrol acetate 160 to 800 mg daily, and nutrition support.
• Dyspnoea, cough and secretions: low-dose oral morphine 2.5 to 5 mg, hyoscine butylbromide 20 mg subcutaneously, and oxygen only for hypoxia.

Differences. Pegfilgrastim is given once each cycle; filgrastim is daily and cheaper. Zoledronic acid is renally cleared; denosumab is not but causes hypocalcaemia and rebound fractures when stopped.

• Growth factor prophylaxis: use primary prophylaxis when the risk of febrile neutropenia is 20 percent or more (or 10 to 20 percent with risk factors), and secondary prophylaxis after a previous episode when dose reduction would harm cure.
• Neutropenic sepsis (neutrophils under 0.5 x 10^9/L with fever 38.0 degrees Celsius or more): an emergency; use risk scoring to select outpatients; reassess at 48 hours and narrow cover by cultures.
• Anaemia: transfuse for haemoglobin under 7 to 8 g/dL or symptoms; erythropoiesis-stimulating agents only with chemotherapy and haemoglobin under 10 g/dL (raise thrombotic and progression risk); give iron when deficient.
• Cancer-associated thrombosis: treat for at least 3 to 6 months and while cancer is active; primary prophylaxis in selected ambulatory patients at high risk.
• Bone disease: give bone-modifying agents in myeloma and for bone metastases from breast, prostate and other solid tumours; complete a dental review first.
• Hepatitis B: give prophylaxis (entecavir or tenofovir) for patients with positive surface antigen or core antibody before chemotherapy.
• Regional: liquid or tablet morphine is the main opioid; availability is limited by supply and prescribing restrictions; plan pain control early and teach families to administer.

Selection. Match each intervention to a defined risk or symptom, review regularly, and stop interventions that no longer help.

Contraindications. Filgrastim and pegfilgrastim: hypersensitivity; use with caution in sickle cell disease. Bisphosphonates: severe kidney impairment (zoledronic acid), uncorrected hypocalcaemia. Morphine: respiratory depression, paralytic ileus, acute asthma.

Adverse effects. Growth factors: bone pain (loratadine or naproxen), splenic rupture, leucocytosis. Zoledronic acid: acute phase reaction, kidney injury, hypocalcaemia, osteonecrosis of the jaw, atypical femoral fracture. Denosumab: hypocalcaemia, osteonecrosis of the jaw. Morphine: constipation, nausea, sedation, delirium, respiratory depression, myoclonus. Corticosteroids: hyperglycaemia, infection, psychosis, myopathy. Anticoagulants: bleeding.

Interactions. Morphine with benzodiazepines and gabapentinoids adds respiratory depression; zoledronic acid with aminoglycosides and loop diuretics increases kidney and calcium effects; apixaban with strong CYP3A4 and P-glycoprotein inhibitors or inducers (ritonavir, rifampicin) is unsafe; warfarin with capecitabine and antibiotics.

Special groups.

• Pregnancy: avoid most bone-modifying agents; filgrastim and heparins are used.
• Breastfeeding: morphine in small doses is acceptable; avoid bisphosphonates.
• Children: use weight-based doses; avoid aspirin.
• Older adults: lower opioid, gabapentin and steroid doses; falls risk.
• Kidney impairment: reduce morphine (use oxycodone or fentanyl in severe impairment), zoledronic acid and gabapentin.
• Liver impairment: lower opioid doses and longer intervals.

Monitoring. Daily pain and bowel review, pain scores, calcium, magnesium and creatinine before bone-modifying agents, full blood count, temperature, blood pressure, oral and skin inspection, and cumulative toxicity.

Referral and escalation. Fever in a neutropenic patient, new back pain with leg weakness or bladder disturbance, hypercalcaemic confusion, uncontrolled pain, bleeding, and suspected thrombosis need emergency care.