PharmacologyTier 1Medical Sciences concept

Chemotherapy agent characteristic toxicities

Core concept

Every agent shares myelosuppression, mucositis, alopecia and nausea. The exam tests the toxicity that belongs to one drug and no other.

Agent	Signature toxicity
Bleomycin	Pulmonary fibrosis - dose-related (>400 units), worse with high FiO2 and renal impairment; no myelosuppression
Doxorubicin / anthracyclines	Dose-dependent cardiomyopathy (cumulative >450-550 mg/m2); red urine; severe vesicant extravasation
Cisplatin	Nephrotoxicity, ototoxicity (high-frequency, irreversible), peripheral neuropathy, Mg wasting, and the most emetogenic drug in use
Oxaliplatin	ACUTE COLD-INDUCED dysaesthesia of hands, feet and perioral region within hours-days, reversible; plus a separate chronic cumulative sensory neuropathy. Renal-sparing and far less ototoxic than cisplatin
Carboplatin	Myelosuppression (thrombocytopenia); dosed by AUC (Calvert formula); hypersensitivity after ~6+ cycles
Vincristine	Peripheral and autonomic neuropathy, ileus, SIADH; fatal if given intrathecally; no myelosuppression
Vinblastine	Myelosuppression (the mirror image of vincristine)
Paclitaxel	Sensory neuropathy, hypersensitivity to the cremophor vehicle (premedicate), myalgia
Docetaxel	Fluid retention/oedema, nail changes, neutropenia
Cyclophosphamide / ifosfamide	Haemorrhagic cystitis (acrolein) -> mesna + hydration; bladder cancer, infertility, SIADH; ifosfamide -> encephalopathy (methylene blue)
Methotrexate	Mucositis, myelosuppression, hepatotoxicity, pneumonitis, renal tubular precipitation at high dose -> alkalinise + hydrate + folinic acid rescue; NSAIDs and trimethoprim are dangerous
5-FU / capecitabine	Palmar-plantar erythrodysaesthesia, mucositis, diarrhoea, coronary vasospasm; DPD deficiency -> life-threatening toxicity
Irinotecan	Early cholinergic diarrhoea (atropine) and late secretory diarrhoea (loperamide); *UGT1A128 -> severe neutropenia**
Cytarabine	Cerebellar toxicity at high dose, conjunctivitis (steroid eye drops)
Bleomycin, busulfan, methotrexate, nitrosoureas	The pulmonary toxicity group
Asparaginase	Pancreatitis, thrombosis, hyperglycaemia, hypofibrinogenaemia

Key detail

Targeted and immune agents

Agent	Toxicity
Trastuzumab	Reversible cardiotoxicity, NOT dose-dependent - contrast with anthracyclines; monitor LVEF 3-monthly
Bevacizumab (VEGF)	Hypertension, proteinuria, arterial thrombosis, impaired wound healing, GI perforation, haemorrhage
EGFR inhibitors (cetuximab, erlotinib)	Acneiform rash (correlates with response), hypomagnesaemia, diarrhoea
Checkpoint inhibitors	Immune-related AEs - colitis, hepatitis, thyroiditis, hypophysitis, pneumonitis, myocarditis
CAR-T	Cytokine release syndrome, ICANS
Tyrosine kinase inhibitors	QT prolongation (many), hypothyroidism (sunitinib), hepatotoxicity

Cross-cutting

Febrile neutropenia is the emergency - broad-spectrum antibiotics within 1 hour, before imaging
Tumour lysis syndrome - high-grade lymphoma, ALL, bulky disease -> hydration + allopurinol, or rasburicase if high-risk (rasburicase is contraindicated in G6PD deficiency)
Emetogenicity determines antiemetics: high (cisplatin, AC) -> 5-HT3 antagonist + dexamethasone + NK1 antagonist (aprepitant) +/- olanzapine

Clinical relevance

Baseline organ testing matched to the drug: DLCO before bleomycin, echo before anthracyclines and trastuzumab, audiometry and eGFR before cisplatin, DPD genotype before 5-FU/capecitabine, UGT1A1 before irinotecan, TPMT/NUDT15 before thiopurines
*Tell the anaesthetist about prior bleomycin* - keep FiO2 as low as possible for life
Late effects: secondary MDS/AML (alkylators at 5-7 yr with -5/-7; topoisomerase II inhibitors at 1-3 yr with 11q23), infertility, cardiac failure decades later, second solid tumours after radiotherapy
Fertility preservation must be discussed BEFORE the first cycle - alkylating agents are the most gonadotoxic

Correlations

Chemotherapy drug mechanisms of action by class
Cell cycle phases and drug-induced cell cycle arrest
Alkylating agent gonadotoxicity; cytogenetics of therapy-related myeloid neoplasms
Chemotherapy-induced nausea and vomiting - neurotransmitter targets
CYP2D6 and other pharmacogenomics

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