Hematology, Oncology & Immunology · Topic 20 of 26

Chemotherapy Toxicities & Extravasation

Oncology pharmacology · chemotherapy toxicity

Chemotherapy Toxicities & Extravasation

Know each drug's signature harm — marrow, heart, kidney, nerve, lung — and treat a vesicant leak by drug: dexrazoxane and ice for anthracyclines, hyaluronidase and warmth for vincas.

Key numbers

Neutropenia: infection risk soars below 500/µLANC < 500/µL

Anthracycline leak: ice plus dexrazoxanedexrazoxane within 6 h

Anthracycline cardiomyopathy is cumulativedoxorubicin > 550 mg/m²

G-CSF when febrile neutropenia risk exceeds 20%FN risk > 20%

Neutrophil nadir 7–14 days after chemotherapynadir day 7–14

01 · GiveAnthracycline leak: ice plus dexrazoxane

Anthracycline extravasation: apply ice 15 minutes 4 times daily for 3 days and give IV dexrazoxane for 3 days (1,000, 1,000, then 500 mg/m²), starting within 6 hours.

02 · GiveVinca leak: hyaluronidase and warmth, no ice

Vinca alkaloid (vincristine, vinblastine) extravasation: inject hyaluronidase locally and apply moderate heat to disperse the drug; cold packs worsen vinca ulceration and are avoided.

03 · Watch forAnthracycline cardiomyopathy is cumulative

Anthracycline cardiomyopathy is cumulative: 1–20% at doxorubicin 300–500 mg/m², with risk rising further above 550 mg/m² and with other cardiotoxic therapy; measure LVEF before, during and after treatment.

Causes & risk factors

Why it happens

Know the vesicantsVesicants include the anthracyclines (doxorubicin, daunorubicin), vinca alkaloids (vincristine, vinblastine), mitomycin and paclitaxel; DNA-binding vesicants keep killing cells, so necrosis can progress for weeks.

Diagnosis & monitoring

Work-up

Trastuzumab: check LVEF every 3 monthsTrastuzumab causes LV dysfunction, worst with anthracyclines: check LVEF at baseline and every 3 months; hold at least 4 weeks for a ≥ 16% absolute drop, or a ≥ 10% drop to below normal.

Neutrophil nadir 7–14 days after chemotherapyThe neutrophil nadir usually falls 7–14 days after a chemotherapy dose (several weeks with nitrosoureas); infection risk tracks the depth and duration of the nadir, so fever in that window is neutropenic until proven otherwise.

Do right now

In this order

First moves

Extravasation: stop, aspirate, do not flush

→

Anthracycline leak: ice plus dexrazoxanedexrazoxane within 6 h

→

Vinca leak: hyaluronidase and warmth, no ice

Why each step

Extravasation: stop, aspirate, do not flushAt suspected vesicant extravasation stop the infusion, leave the cannula in to aspirate residual drug, do not flush or press on the site, elevate the limb, then give the drug-specific antidote and thermal treatment.

Anthracycline leak: ice plus dexrazoxaneAnthracycline extravasation: apply ice 15 minutes 4 times daily for 3 days and give IV dexrazoxane for 3 days (1,000, 1,000, then 500 mg/m²), starting within 6 hours.

Vinca leak: hyaluronidase and warmth, no iceVinca alkaloid (vincristine, vinblastine) extravasation: inject hyaluronidase locally and apply moderate heat to disperse the drug; cold packs worsen vinca ulceration and are avoided.

Management

Orders

G-CSF when febrile neutropenia risk exceeds 20%Give prophylactic myeloid growth factor with regimens carrying > 20% febrile neutropenia risk: filgrastim 5 mcg/kg SC daily or pegfilgrastim 6 mg once per cycle — not within 24 hours after chemotherapy.

Ifosfamide needs mesna and hydrationIfosfamide causes hemorrhagic cystitis — give mesna with every dose and at least 2 L/day of fluid — plus encephalopathy and nephrotoxicity, all in its boxed warning.

High-dose methotrexate: leucovorin, glucarpidase if delayedHigh-dose methotrexate needs leucovorin rescue; for toxic levels (> 1 µmol/L) with delayed clearance from impaired renal function, give glucarpidase 50 units/kg IV, separating leucovorin by 2 hours.

Mucositis: oral care and cryotherapy for 5-FUPrevent oral mucositis with basic oral care and 30 minutes of oral cryotherapy (ice chips) during bolus 5-fluorouracil; treat with anesthetic rinses (viscous lidocaine), a bland diet and analgesics, and treat candidiasis.

Transfuse platelets below 10,000/µLChemotherapy-induced thrombocytopenia raises bleeding risk as the count falls; platelets below 10,000/µL need transfusion, and NSAIDs and aspirin are avoided.

Red flags & don'ts

Avoid harm

Cisplatin: nephrotoxicity, low magnesium, hearing loss complicationCisplatin causes cumulative nephrotoxicity (prevent with IV hydration, sometimes mannitol), electrolyte wasting (magnesium, potassium, calcium), cumulative ototoxicity (audiometry before each dose), neuropathy and severe emesis; aminoglycosides potentiate kidney injury.

Bleomycin causes pneumonitis and pulmonary fibrosis complicationBleomycin causes pulmonary toxicity in about 10% — pneumonitis that can progress to fatal fibrosis (about 1%) — more often after age 70 and above 400 units total dose.

Vincristine is IV only — fatal intrathecally avoidVincristine's dose-limiting toxicity is neurotoxicity (neuropathy, constipation); it is labeled “for intravenous use only — fatal if given by other routes”, because intrathecal injection is lethal.

The rules

Know these

Neutropenia: infection risk soars below 500/µL must knowMyelosuppression is the common dose-limiting toxicity: neutropenia is ANC < 1,500/µL, infection risk rises sharply below 500/µL, and fever with neutropenia is an emergency needing cultures and immediate broad-spectrum antibiotics (see Neutropenic Fever).

Anthracycline or vinca alkaloid extravasation?

Commonly confused

Examples	Doxorubicin, daunorubicin
Strategy	Localize and neutralize
Local temperature	Ice 15 minutes, 4 times a day for 3 days
Antidote	IV dexrazoxane for 3 days, first dose within 6 hours

More detail

Reference

Show 7 reference facts

Dexrazoxane is also a cardioprotectant, labeled for metastatic breast cancer after a cumulative doxorubicin dose of 300 mg/m² when doxorubicin continues; it is not started with the first anthracycline dose.

Sodium thiosulfate is the recommended local antidote for mechlorethamine (nitrogen mustard) extravasation.

MASCC/ISOO also suggests oral cryotherapy with high-dose melphalan before stem cell transplant and palifermin (keratinocyte growth factor) to prevent mucositis with high-dose conditioning.

For highly emetogenic chemotherapy such as cisplatin, combine a 5-HT₃ antagonist with dexamethasone and an NK1 antagonist (aprepitant); lorazepam helps anticipatory nausea.

Allow at least 14 days between pegfilgrastim and the next chemotherapy dose.

Avoid rectal thermometers, enemas and suppositories in patients with neutropenia or thrombocytopenia.

Extravasation strategy follows the drug: localize and neutralize (cold, antidote) for DNA-binding vesicants such as anthracyclines; spread and dilute (warmth, hyaluronidase) for non-DNA-binding vesicants such as vinca alkaloids.

Pearl

Anthracycline leaks get ice and dexrazoxane; vinca leaks get heat and hyaluronidase — never ice a vinca.