Key Facts

Cytotoxic chemotherapy targets rapidly dividing cells and remains a cornerstone of cancer treatment. Drugs are classified by mechanism of action and cell cycle specificity.

Epidemiology

Approximately 375,000 new cancer cases are diagnosed annually in the UK. Chemotherapy is used in approximately 30% of cancer treatments, either as curative intent, adjuvant, neoadjuvant, or palliative therapy.

Aetiology

Chemotherapy agents are classified by mechanism:

• Alkylating agents: Form covalent bonds with DNA bases (cyclophosphamide, melphalan, busulfan)
• Antimetabolites: Structural analogues that interfere with nucleotide synthesis (methotrexate, 5-FU, gemcitabine)
• Cytotoxic antibiotics: DNA intercalation and free radical generation (doxorubicin, bleomycin)
• Plant-derived agents: Vinca alkaloids (microtubule inhibitors), taxanes (microtubule stabilisers), topoisomerase inhibitors
• Platinum compounds: DNA cross-linking (cisplatin, carboplatin, oxaliplatin)

Pathophysiology

Chemotherapy exploits the higher growth fraction of tumour cells compared to normal tissues. The log-kill hypothesis states that each cycle kills a constant proportion of cells. Combination chemotherapy uses drugs with different mechanisms and toxicity profiles to maximise efficacy and minimise resistance.

Common Toxicities

• Bone marrow suppression: Neutropenia (nadir 7-14 days), thrombocytopenia, anaemia
• GI toxicity: Nausea/vomiting (classified as high/moderate/low emetogenic), mucositis, diarrhoea
• Alopecia: Common with anthracyclines, taxanes, cyclophosphamide
• Infertility: Alkylating agents particularly gonadotoxic

Red Flags — Oncological Emergencies

• Neutropenic sepsis: Fever ≥38°C with neutrophils <0.5×10⁹/L — treat within 1 hour
• Tumour lysis syndrome: Metabolic derangement within 12-72 hours of treatment
• Superior vena cava obstruction: Facial swelling, dyspnoea, dilated chest wall veins
• Spinal cord compression: Back pain, lower limb weakness, urinary retention
• Hypercalcaemia of malignancy: Confusion, polyuria, constipation

Bedside

• Observations: Temperature, HR, BP, SpO2 — assess for sepsis
• Fluid balance: Particularly important in tumour lysis syndrome
• ECG: QT prolongation risk with some agents, arrhythmias in tumour lysis

Bloods

• FBC: Nadir check (typically day 10-14), monitor for pancytopenia
• U&Es: Renal function monitoring, electrolytes in tumour lysis
• LFTs: Hepatotoxicity screening (methotrexate, 6-mercaptopurine)
• Urate: Elevated in tumour lysis syndrome
• Blood cultures: If febrile — before antibiotics

Imaging

• CXR: Bleomycin pulmonary toxicity, infection
• CT staging: Assess treatment response (RECIST criteria)
• Echocardiogram: Baseline and surveillance with anthracyclines

Special Tests

• MUGA scan: Cardiac function monitoring with cardiotoxic agents
• Audiometry: With cisplatin
• Pulmonary function tests: With bleomycin (DLCO)

Non-pharmacological

• Fertility preservation: Sperm banking, oocyte cryopreservation before treatment
• Patient education: Neutropenic sepsis awareness, when to seek emergency care
• Scalp cooling: To reduce alopecia with certain regimens

Pharmacological

Antiemetic prophylaxis (NICE NG12 — Antiemetics):

• High emetogenic risk (cisplatin): Dexamethasone 8mg + 5-HT3 antagonist (ondansetron 8mg) + NK1 antagonist (aprepitant 125mg day 1, 80mg days 2-3)
• Moderate risk: Dexamethasone + 5-HT3 antagonist
• Low risk: Dexamethasone or metoclopramide PRN

Neutropenic sepsis (NICE NG151):

• Empirical antibiotics within 1 hour of presentation
• Piperacillin-tazobactam 4.5g TDS IV (or per local guidelines)
• Add gentamicin if septic shock
• G-CSF (filgrastim) for primary/secondary prophylaxis in high-risk regimens

Tumour lysis prevention:

• Allopurinol 300mg OD starting 2-3 days before treatment
• Rasburicase 0.2mg/kg IV if high risk (breaks down urate)
• Aggressive IV hydration

Referral Criteria

• All chemotherapy prescribing by specialist oncology teams
• Cardiology review if LVEF drops >10% or below 50%
• Respiratory review if DLCO drops >20% on bleomycin

• Chemotherapy cure rates vary widely: >90% for testicular cancer, <5% for pancreatic cancer
• Neutropenic sepsis mortality: 5-10% with prompt treatment, much higher if delayed
• Anthracycline cardiomyopathy: Risk increases above cumulative dose of 450mg/m² for doxorubicin
• Bleomycin pulmonary fibrosis: Occurs in ~10% of patients, can be fatal
• Second malignancies: Alkylating agents increase risk of myelodysplasia and AML (latency 5-7 years)

Key Chemotherapy Agents and Their Toxicities

Performance Status Scales