Table 3.

Common adverse reactions to oncolytic virotherapies.

Virus type	Oncolytic virus	Engineering for specificity	Clinical Trials.gov identifier	Indication	Common adverse events	Severe adverse events	References
HSV	T-VEC	ICP34.5 deletion; US11 deletion; Human GM-CSF insertion	NCT02288897 NCT01740297 NCT01368276 NCT00289016	Melanoma	Grade I-II flulike symptoms (fever, fatigue, nausea, vomiting), local injection reaction (inflammation, erythema and rash at the injection site)	Severe hypotension, tachycardia, cellulitis, dyspnea, pleural effusion	(77)
	HSV1716	ICP34.5 deletion	NCT02031965 NCT01721018	High grade glioma, malignant pleural mesothelioma	Flulike symptoms, headache, back pain	Urinary tract infection, hydrocephalus, seizures, varicella zoster infection	(104)
	G207	ICP34.5 deletion; UL39 disruption	NCT03911388 NCT02457845 NCT00028158	Cerebellar tumor, supratentorial brain tumor	Flulike symptoms, anemia, leukopenia	Brain edema, speech disorder, encephalitis, hepatitis, viral infection	(105, 106)
	HF10	Spontaneously attenuated HSV-1 mutant	NCT02428036 NCT03259425 NCT03252808 NCT03153085	Melanoma, squamous cell carcinoma of the skin, pancreatic cancer	Flulike symptoms, neutropenia, liver dysfunction	Perforated peritonitis, severe liver dysfunction	(107, 108)
	OH2	ICP34.5 deletion; ICP47 deletion; hGM-CSF insertion	NCT03866525	Intestinal cancer
Adenovirus	VCN-01	E1A deletion; E2F1 insertion; Replace KKTK with RGDK	NCT02045602 NCT02045589	Solid tumor, pancreatic cancer	Weight loss, elevated liver enzymes, thrombocytopenia (rat)	Viremia (rat)	(74)
	CG0070	E3 deletion; GM-CSF insertion	NCT02365818	Bladder Cancer	Bladder spasm, hematuria, dysuria, urgency, flulike symptoms	Severe dysuria, hypotension	(75)
	Ad5-Δ24-RGD	RGD, Delta-24	NCT0056203 NCT01582516	Breast cancer, glioblastoma	Grade I-II flulike symptoms, abdominal pain, anemia, glucose abnormalities	Pleural effusion, dehydration, intestinal obstruction, hypokalemia	(91)
	H101	E1B deletion; Duplication only in p-53 deficient cancer cells			Flulike symptoms, fever, injection site pain, leukopenia, liver dysfunction, hair loss	Severe leukopenia, severe liver dysfunction	(82, 83, 86, 109)
	Onyx-015	E1B deletion			Fever, elevated liver enzymes	Dehydration, hypotension, sepsis	(85)
	CGTG-102	SSTR, TK, RGD, Ad5/3, GM-CSE, Delta-24	NCT01437280 NCT01598129	Solid tumor	Grade I-II flulike symptoms, mild electrolyte disturbances, elevated liver enzymes, anemia	Dyspnea, pulmonary embolism	(84, 101)
	LOAd703	Trimerized CD40L and 4-1BBL (110)	NCT02705196	Pancreatic cancer
	ICOVIR-5	DM-1 insertion; E2F1 insertion; Kozak insertion; E1A-Δ24 deletion; RGD deletion (111)	NCT01864759	Melanoma	Flulike symptoms, elevated liver enzymes, thrombocytopenia	Severe transaminase elevation, edema	(92)
Pox virus	JX-594	TK deletion; GM-CSF insertion	NCT03206073 NCT02562755 NCT01394939 NCT01387555 NCT00429312	Colorectal cancer, hepatocellular carcinoma, melanoma	Flulike symptoms, hypotension, tachycardia, hypertension, anorexia, myalgia	Pustules, severe leukopenia, severe lymphopenia, severe fever, hypokalemia, severe headache	(93, 94)
	vvDD	VGF deletion;TK deletion
	GL-ONC1	Attenuated poxvirus, lister strain	NCT02759588 NCT01584284 NCT00794131	Ovarian cancer, head and neck cancer, solid tumor	Flulike symptoms, anorexia, back pain	Pancreatitis	(96)
Reovirus	Reolysin	Wild type	NCT00651157 NCT01533194 NCT01240538 NCT00602277 NCT00503295	Melanoma, multiple myeloma, solid tumor in children, ovarian epithelial cancer, peritoneal cancer	Flulike symptoms, neutropenia, diarrhea	Severe neutropenia, severe diarrhea, elevated liver enzymes, dehydration	(60)
Coxsackie virus	Cavatak	None	NCT00832559 NCT00438009	Head and neck cancer, melanoma
Measles virus	MV-CEA	CEA	NCT00390299 NCT00408590	Ovarian epithelial cancer, primary peritoneal cancer, fallopian tube cancer	Flulike symptoms, abdominal pain, anorexia	Arthralgia	(78)
	MV-NIS	NIS	NCT02192775 NCT03456908 NCT02919449 NCT03171493 NCT01503177	Multiple myeloma, non-small cell lung cancer, urothelial carcinoma, malignant pleural mesothelioma	Grade I-II flulike symptoms, leukopenia, diarrhea, neutropenia	Neutropenia, leukopenia, anemia	(112)
Newcastle disease virus	NVD	None	NCT01174537	Glioblastoma, sarcoma, neuroblastoma
Parvovirus	H-1PV	None	NCT01301430	Multiforme glioblastoma		Biliary duct proliferation, hydrocephalus, decreased consciousness	(113, 114)