General principles
• Non-specific cytotoxic agents → target rapidly dividing cells (cancer cells, but also
hair follicles, GI mucosa, bone marrow)
• Often used in combination regimens to:
o Reduce resistance
o Synergistic effects
o Allow lower individual doses (decreasing toxicity)
Common side effects
• Myelosuppression
o Neutropenia → febrile neutropenia → sepsis risk
o Thrombocytopenia → bleeding
o Anaemia → fatigue
• Mucositis
o Painful ulcerations throughout GI tract → risk of infection, nutrition compromise
• Nausea/vomiting
o Emetogenic potential varies; managed with 5-HT₃ antagonists (ondansetron), NK1 inhibitors, dexamethasone
• Alopecia
o Reversible, emotionally distressing
• Infertility
o Due to gonadal toxicity; consider sperm/oocyte preservation
• Other toxicities
o Anthracyclines (e.g., doxorubicin): cardiomyopathy
o Cisplatin: nephrotoxicity, ototoxicity, peripheral neuropathy
o Cyclophosphamide: haemorrhagic cystitis (prevent with mesna)
• Act on specific molecular targets (mutant proteins, growth factor pathways)
Examples
o Inhibits BCR-ABL tyrosine kinase (CML)
o Also active against KIT mutations (gastrointestinal stromal tumours, GIST)
o Erlotinib, gefitinib
o Effective in NSCLC with activating EGFR mutations
o Side effects: acneiform rash (rash is predictive of response), diarrhoea
o Monoclonal antibody against HER2 (ERBB2 receptor)
o Used in HER2+ breast and gastric cancers
o Cardiotoxicity: risk of reversible heart failure; monitor LVEF (echo)
o Anti-VEGF monoclonal antibody
o Used in colorectal, renal, and other solid tumours
o Side effects: hypertension, proteinuria, impaired wound healing, risk of bleeding and GI perforation
• Uses the host immune system to attack cancer cells
• Particularly effective in tumours with high mutational burden
Examples
• Checkpoint inhibitors
o PD-1 inhibitors: nivolumab, pembrolizumab
o CTLA-4 inhibitor: ipilimumab
• Indications
o Melanoma
o NSCLC (especially PD-L1 high expressors)
o Renal cell carcinoma
o Hodgkin lymphoma
Side effects
• Immune-related adverse events (irAEs)
o Colitis → diarrhoea
o Pneumonitis → cough, dyspnoea
o Hypophysitis → adrenal insufficiency, hypothyroidism
o Hepatitis → LFT derangements
• Managed with immunosuppression (e.g., steroids)
Breast cancer
• Tamoxifen
o Selective estrogen receptor modulator (SERM)
o Used in pre- and postmenopausal ER+ breast cancer
o Side effects: increased risk of endometrial carcinoma, venous thromboembolism (VTE), menopausal symptoms
• Aromatase inhibitors (e.g., anastrozole, letrozole)
o Inhibit peripheral conversion of androgens to oestrogens
o Indicated in postmenopausal ER+ breast cancer
o Side effects: osteoporosis (fracture risk), arthralgia, hypercholesterolaemia
Prostate cancer
• Androgen deprivation therapy (ADT)
o Methods: LHRH agonists (e.g., leuprolide), orchiectomy, anti-androgens (e.g., bicalutamide)
o Used in advanced or metastatic disease
o Side effects:
Hot flushes
Osteoporosis
Metabolic syndrome (weight gain, insulin resistance, dyslipidaemia)
Loss of libido, erectile dysfunction
• Febrile neutropenia: treat immediately with broad-spectrum IV antibiotics (e.g., piperacillin-tazobactam)
• Trastuzumab and anthracyclines together → additive cardiotoxicity; avoid concurrent use
• VEGF inhibitors → avoid surgery or delay wound healing due to anti-angiogenesis effects
• Anti-EGFR therapy (cetuximab) in colorectal cancer only effective if KRAS wild type
• Immunotherapy → potential for durable responses ("tail" on survival curves)
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Author & Educational Disclaimer
Author:
Dr Phillip Cockrell BM FRCP DipClinEd
Dr Phillip Cockrell is a UK Consultant Physician in Internal Medicine, currently working at Queen Alexandra Hospital, Portsmouth University Hospitals NHS Trust. He has previously worked as a registrar across Intensive Care Medicine, Gastroenterology, Cardiology, Stroke Medicine, Acute Medicine, and Respiratory Medicine.
He has held senior leadership roles including Associate Clinical Director of the Acute Medical Unit, Clinical Director of Internal Medicine, and Chief of Medicine. Dr Cockrell has over 15 years’ experience in postgraduate medical education, having lectured extensively across the MRCP syllabus and contributed to MRCP revision teaching and course development.
Dr Cockrell holds a Bachelor of Medicine (BM), Fellowship of the Royal College of Physicians (FRCP), and a Diploma in Clinical Education (DipClinEd). His teaching approach is based on structured consolidation of complex medical topics to support efficient and effective revision for postgraduate examinations.
Purpose of this content:
The material on this page is intended solely for educational purposes to support revision for the MRCP (UK) Part 1 examination. It reflects examination-relevant principles of internal medicine and is designed to aid learning and pattern recognition.
Medical disclaimer:
This content is designed for postgraduate medical examination revision and does not constitute medical advice, diagnosis, or treatment guidance and must not be used as a substitute for professional clinical judgement, local guidelines, or specialist consultation. Clinical decisions should always be made in the context of individual patient circumstances and current national guidance.
