Chemotherapy

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)

Targeted therapies

•    Act on specific molecular targets (mutant proteins, growth factor pathways)

Examples

•    Imatinib

o    Inhibits BCR-ABL tyrosine kinase (CML)

o    Also active against KIT mutations (gastrointestinal stromal tumours, GIST)

•    EGFR inhibitors

o    Erlotinib, gefitinib

o    Effective in NSCLC with activating EGFR mutations

o    Side effects: acneiform rash (rash is predictive of response), diarrhoea

•    Trastuzumab

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)

•    Bevacizumab

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

Immunotherapy

•    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)

Hormonal therapy

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

Extra Revision Pearls

•    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)