Therapy Toxicities

Rahul Shah

AJ Winer

Immune Checkpoint Inhibitor Toxicities

Immune checkpoint inhibitors augment the endogenous immune response against tumors, which may lead to autoimmune-like toxicities, known as immune-related adverse events (irAEs)
Treatment: low-dose glucocorticoids (prednisone, 0.5 mg/kg) for mild adverse events, high dose glucocorticoids (prednisone, 1-2 mg/kg) for severe adverse events. Depending on the irAE severity, future ICI therapy may be permanently discontinued.

Adverse Event Type	Incidence with anti-CTLA-4 (e.g. ipilimumab)	Incidence with anti-PD1/PD-L1 (e.g. nivolumab, pembrolizumab)
Skin (rash, pruritus, TEN)	30%	30%
Colitis	25%	5%
Hypothyroidism	20%	20%
Hepatitis	10%	1%
Hypophysitis	10%	rare
Pneumonitis	2-5%	2-5%
Myocarditis	<1%	<1%
Neurotoxicity (GBS, myasthenia gravis, encephalitis)	<1%	<1%

Cytotoxic Agent Toxicities

Class	Agent	Side Effect
Alkylating agents	busulfan	pulmonary fibrosis or diffuse alveolar hemorrhage
	cyclophosphamide	myopericarditis, hemorrhagic cystitis (prevention: hydration; monitoring: daily UA, tx: mesna)
	ifosfamide	encephalopathy (tx: methylene blue), nephrotoxicity, hemorrhagic cystitis
Antimetabolites	5- Fluorouracil (5-FU)/ Capecitabine (metabolized to FU)	myelosuppression, coronary vasospasm, palmar-plantar erythrodysesthesia, mucositis
	cladribine, pentostatin	dose reduced for CrCl
	cytarabine (Ara-C)	irreversible cerebellar ataxia (if high dose, neuro checks required), conjunctivitis (prevent with prophylactic steroid eye drops)
	gemcitabine	transient transaminitis, peripheral edema, rash, rarely: pulmonary toxicity, hemolytic uremic syndrome, capillary leak syndrome, PRES
	methotrexate	stomatitis, hepatotoxicity, renal failure, high dose requires leucovorin
Antitumor antibiotics	anthracyclines (doxorubicin, daunorubicin, idarubicin)	HFrEF (need TTE prior). Most notable with doxorubicin.
Antitumor antibiotics	bleomycin	Pulmonary fibrosis. Potentiated with G-CSF
Monoclonal antibodies	alemtuzumab	severe and prolonged cytopenias
	bevacizumab
	rituximab	hypophos, hepatotoxicity, HBV reactivation (screen all pts), peripheral neuropathy; transfusion reaction during 1st time infusion
Platinum agents	cisplatin, oxaliplatin, carboplatin	Nephrotoxicity, worst with cisplatin. Rental tubular acidosis. Neurotoxicity (parasthesias, cold sensitivity, cramps, peripheral neuropathy), ototoxicity (high frequency hearing loss), constipation, hypomag
Taxanes	docetaxel, paclitaxel	hypersensitivity reaction (often require premedication with steroids and H1/H2 blockers); peripheral neuropathy
Topoisomerase inhibitors	irinotecan, topotecan, etoposide	irinotecan- acute diarrhea can be treated with atropine; delayed with imodium/Lomotil
Tyrosine kinase inhibitors	imatinib, dasatinib, nilotinib, bosutinib	QTc prolongation, pulmonary effusion, hepatotoxicity
Vinca alkaloid	vincristine	peripheral neuropathy and ototoxicity (vestibular system lost first)

Other treatments and toxicities

Agent	Adverse event(s)	Management
Belzutifan	Anemia and hypoxia	Stop belzutifan, transfuse, supplement O2
BiTE/BiAb/ CAR T Cells	Cytokine release syndrome, ICANS	See CAR T Cell Section
Radiation Therapy	See Radiation Toxicity section (ie Skin, HEENT, GI)	See Radiation Toxicity section

Last updated on August 27, 2025