Table 1.

Cytotoxic drugs used to treat cancers and their effects on PD-(L)1

Drug category	#	INN	Abbreviation	Brand namea	Year of first approvalb	Effect on PD-(L)1
Antimetabolites	1	5-Fluorouracil	5-FU	5-Fluorouracil	1962	Combo (+). Expression (+)
Pyrimidine analogues	2	Capecitabine	CAP	Xeloda	1998	Combo (+)
	3	Trifluridine	FTD	Lonsurf	2014	Combo (+)
	4	Gemcitabine	GEM	Gemcitabine	1995	Combo (+). Expression (+)
	5	Cytarabine	Ara-C	Cytarabine	1969	Combo (+)
	6	Cytarabine/daunorubicin liposomal	CPX-351	Vyxeos	2017	n.i.
Purine analogues	7	Fludarabine	2-FA	Fludara	1991	No effect
	8	Cladribine	CLA	Leustatin	1993	n.i.
	9	Clofarabine	CLO	Clolar	2005	n.i.
	10	Nelarabine	NEL	Arranon	2006	n.i.
Folate derivatives	11	Methotrexate	MTX	Methotrexate	1954	Combo (−)
	12	Pralatrexate	PLX	Folotyn	2009	Combo (−)
	13	Pemetrexed	PMX	Alimta	2004	Combo (+)
	14	Raltitrexed	RTX	Tomudex	1996	n.i.
DNMT inhibitors	15	Azacitidine	5-AZA	Vidaza	2004	Combo (+). Expression (+)
	16	Decitabine	DAC	Dacogen	2006	Combo (+). Expression (+)
DNA-alkylating drugs	17	Cisplatin	CDDP	Cisplatin	1978	Combo (+). Expression (+)
Platinum derivatives	18	Oxaliplatin	OXA	Eloxatin	1996	Combo (+). Expression (+)
	19	Carboplatin	CARB	Paraplatin	1986	Combo (+). Expression (+)
	20	Nedaplatin	NEDA	Aqupla	1995	Combo (+)
	21	Lobaplatin	LPT	Lobaplatin	1998	n.i.
	22	Miriplatin	MPT	Miripla	2010	n.i.
Oxazaphosphorine derivatives	23	Cyclophosphamide	CPX	Cytoxan	1957	Combo (+)
	24	Ifosfamide	IFS	Ifex	1976	n.i.
	25	Trofosfamide	TFF	Ixoten	2007	n.i.
Nitrosoureas	26	Carmustine	BiCNU	Gliadel	1977	Combo (+)
	27	Nimustine	ACNU	Nidran	1981	n.i.
	28	Fotemustine	FTM	Muphoran	1989	n.i.
	29	Lomustine	CCNU	CeeNU	1976	n.i.
	30	Semustine	SEMU	Me-CCNU	1977	n.i.
	31	Ranimustine	MCNU	Cymerine	1987	n.i.
	32	Streptozotocin	STZ	Zanosar	1982	Expression (+)
Bis-chloroethyl-amine	33	Mechlorethamine	MCE	Valchlor	1913	n.i.
	34	Bendamustine	BDM	Treanda	2008	n.i.
	35	Chlorambucil	CHB	Leukeran	1956	n.i.
	36	Melphalan	MLP	Alkeran	1961	Combo (+)
	37	Estramustine	EMP	Emcyt	1980	n.i.
Alkyl sulfonates	38	Busulfan	BUS	Busilvex	1954	Expression (+)
	39	Treosulfan	TREO	Trecondi	2004	n.i.
Others	40	Thiotepa	TEPA	Thioplex	1959	n.i.
	41	Temozolomide	TMZ	Temodal	1999	Combo (+)
	42	Mitomycin C	MMC	Mutamycin	1956	Combo (+)
	43	Procarbazine	PRO	Procarbazine	1969	n.i.
	44	Dacarbazine	DTIC	Dacarbazine	1975	Expression (+)
	45	Altretamine	HMM	Hexalen	1990	n.i.
	46	Trabectedin	TBT	Yondelis	2007	Combo (+). Expression (+)
DNA-binding or -cleaving drugs	47	Bleomycin	BLM	Blenoxane	1966	n.i.
	48	Peplomycin	PLM	Pepleo	1981	n.i.
	49	Mithramycin	MTM	Plicamycin	1961	n.i.
	50	Actinomycin D	Act-D	Cosmegen	1964	Expression (−)
	51	Amsacrine	Amsa	Amsidine	1987	n.i.
Topoisomerase 1 inhibitors	52	Irinotecan	CPT-11, IRI	Campto	1994	Combo (+). Expression (+)
Camptothecin derivatives	53	Topotecan	TPT	Hycamtin	1996	n.i.
	54	Nal-IRI	Nal-IRI	Onivyde	2015	Combo (+)
	55	Belotecan	BLT	Camtobell	2004	n.i.
Topoisomerase 2 inhibitors	56	Etoposide (etoposide phosphate)	VP-16, ETO	Etoposide (Etopophos)	1980 (1996)	Combo (+). Expression (+)
Epipodophyllotoxins	57	Teniposide	VM-26	Vumon	1967	n.i.
Anthracyclines	58	Doxorubicin	DOX	Adriamycin	1966	Combo (+). Expression (+)
	59	Liposomal doxorubicin	Doxil	Doxil	1999	Combo (+). Expression (+)
	60	Epirubicin	EPI	Pharmorubicin	1984	Combo (+)
	61	Idarubicin	IDA	Idamycin	1990	Combo (+)
	62	Daunorubicin	DAU	Cerubidin	1967	n.i.
	63	Pirarubicin	THP	Pinorubicin	1988	n.i.
	64	Amrubicin	AMR	Calsed	2002	n.i.
	65	Valrubicin	VAL	Valstar	1999	n.i.
	66	Aclarubicin	ACLA	Aclacin	1981	n.i.
Anthraquinones	67	Mitoxantrone	MTX	Novantrone	1984	n.i.
	68	Pixantrone	PXT	Pixuvri	2012	n.i.
Tubulin inhibitors	69	Vinorelbine	NVB	Navelbine	1989	Expression (−)
Vinca alkaloids	70	Vindesine	VDS	Eldisine	1979	n.i.
	71	Vinblastine	VBL	Velban	1965	n.i.
	72	Vincristine	VCR	Oncovin	1963	n.i.
	73	Vinflunine	VFL	Javlor	2010	n.i.
Taxanes	74	Paclitaxel	PACLI	Taxol	1993	Combo (+)
	75	Nab-paclitaxel	NABP	Abraxane	2005	Combo (+)
	76	Docetaxel	DOCE	Taxotere	1995	Combo (+)
	77	Cabazitaxel	CBZ	Jevtana	2010	n.i.
Others	78	Ixabepilone	IXA	Ixempra	2007	n.i.
	79	Eribulin mesylate	ERI	Halaven	2010	Combo (+)
Miscellaneous	80	Ingenol mebutate	ING	Picato	2012	n.i.

DNMT: DNA methyl transferase; INN, international nonproprietary name. ^aThe brand name can vary significantly from one country to another and different brand names are used for the generic compounds. ^bThe year of first approval was mainly collected from (1). ‘n.i.’ means no information available about effect of the indicated drug on PD-(L)1. Combo (+) indicates a positive combination potential with mAbs targeting PD-1 or PD-L1. Expression (+) or (−) refers to a drug-induced up- or downregulation of PD-1 or PD-L1.