Adverse drug reactions from - chemotherapy

Reaction types

Reactions span acute infusion-related, short-term dose-limiting, and delayed/cumulative organ toxicities
Pattern is drug-specific enough that toxicity often identifies the agent: cardiotoxicity (anthracyclines), pulmonary fibrosis (bleomycin), peripheral neuropathy (vinca alkaloids, platinums, taxanes), haemorrhagic cystitis (cyclophosphamide/ifosfamide)

Myelosuppression is the most universal dose-limiting toxicity across cytotoxic classes
Cardiotoxicity risk from anthracyclines is cumulative-dose dependent - screening (baseline + surveillance echo/GLS) built into protocols

Myelosuppression: cytotoxic effect on rapidly dividing bone marrow precursors -> neutrophil nadir typically day 7-14 -> febrile neutropenia risk
Anthracyclines (doxorubicin): free radical generation + topoisomerase II-beta inhibition in cardiomyocytes -> dose-dependent, often irreversible cardiomyopathy
Cisplatin: nephrotoxic (proximal tubular), ototoxic, peripheral neuropathy - all cumulative dose-related
Cyclophosphamide/ifosfamide: acrolein metabolite -> haemorrhagic cystitis - mitigated by mesna + hydration
Bleomycin: pulmonary fibrosis, oxygen-dependent toxicity - avoid high FiO2 perioperatively in patients who have received it
Vinca alkaloids/taxanes: microtubule disruption -> peripheral neuropathy (axonal, dose-cumulative)
Tumour lysis syndrome: rapid cell death (esp. high-grade lymphoma/leukaemia) -> hyperkalaemia, hyperphosphataemia, hyperuricaemia, hypocalcaemia -> AKI

Febrile neutropenia: any fever (>=38C) with absolute neutrophil count <0.5 x10^9/L (or expected to fall) is a medical emergency - treat empirically before results available
Baseline + surveillance cardiac imaging (echo/GLS, sometimes troponin) for anthracycline-based regimens
Tumour lysis: UEC, urate, calcium, phosphate pre- and post-treatment in high-risk regimens
Peripheral neuropathy - clinical grading at each cycle, dose-modify/hold before it becomes severe/irreversible

Febrile neutropenia: empirical broad-spectrum antibiotics within 1h (per local protocol), do not wait for neutrophil count to return; G-CSF adjunct in selected high-risk patients
Tumour lysis syndrome prevention: aggressive hydration, rasburicase (or allopurinol for lower-risk) started before/with chemotherapy in high-risk malignancies
Extravasation of vesicant chemotherapy: stop infusion immediately, aspirate residual drug, specific antidotes for some agents (e.g. dexrazoxane for anthracycline extravasation), plastic surgery review if severe
Dose-reduce/delay for cumulative organ toxicity (cardiac, renal, neuropathy) per protocol thresholds
Antiemetic prophylaxis matched to emetogenic risk of the regimen (5-HT3 antagonist +/- NK1 antagonist +/- dexamethasone for highly emetogenic regimens)

Secondary malignancy (leukaemia) from alkylating agents/topoisomerase inhibitors - years later
Infertility - gonadotoxic agents, discuss fertility preservation before starting where relevant
Cumulative cardiotoxicity risk compounds with mediastinal radiotherapy
Myelosuppression recovers within 2-3 weeks per cycle; cumulative organ toxicities (cardiac, renal, neurological) may be permanent once established
Febrile neutropenia mortality is significant without prompt empirical treatment - "door to antibiotic" time is the key modifiable factor

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