. 2023 Feb 15;24(4):3886. doi: 10.3390/ijms24043886

Table 2.

Classes of antineoplastic therapy with potential hypersensitivity reactions [3,8,9,10,11,12,13,14,15,16,17,18].

CLASS	Representatives	Examples	Administration Route	Indications	Hypersensitivity	Adverse Reactions
CLASS	Representatives	Examples	Administration Route	Indications	Hypersensitivity	Cutaneous	Systemic
ALKYLATING AGENTS [10,11]	Nitrogen mustard derivatives	Cyclophosphamide	Oral, IV	Hodgkin or non-Hodgkin acute and chronic lymphatic or myeloid leukemia, malignant lymphomas, OC, BC, LC, neuroblastoma	Anaphylaxis	Urticaria, angioedema, acral erythema, erythema multiformae, nail disorders, stomatitis, vasculitis, SJS, TEN, RRR, pruritus	Pulmonary toxicity, BMS hemorrhagic cystitis, HVOD, EFT, cardiac toxicity, UTRT
		Melphalan	oral	polycythemia vera, multiple myeloma, advanced breast carcinoma, breast adenocarcinoma	Anaphylaxis	Rash, urticaria, angioedema, pruritus, stomatitis, scleroderma, erythema, alopecia	Interstitial pneumonitis pulmonary fibrosis, BMS
		Mechlorethamine	IV	CML, CLL, CTCL, HL, NHL, brain	Anaphylaxis	Urticaria, angioedema ACD, hyper pigmentation, pruritus, erythema multiformae, SJS	Lymphocytopenia
	Triazines	Dacarbazine	IV	malignant melanoma, sarcoma, islet cells, PC, neuroblastoma	Anaphylaxis	Rash, photosensitivity, ISR, urticarial	fever, hypereosinophilia, allergic hepatitis, BMS
	Triazines	Temozolomide	oral	brain cancer, melanoma	Anaphylaxis	Rash, pruritus, photosensitivity, acral erythema, urticaria, pigmentation, MPR, SJS, TEN, alopecia	Fever, peripheral edema, pneumonitis, thrombocytopenia, neutropenia
	Ethylenimines	ThioTEPA	IV, intrathecal, intravesicular	OC, BC, bladder cancer leukemia, multiple myeloma	Anaphylaxis	Rash, urticaria, angioedema, pruritus, pigmentation, ISR, alopecia, dermatitis	Fever, wheezing, BMS, thrombocytopenia, anemia, leukopenia
ANTIMETABOLITES [10,11]	Folate antagonists	Methotrexate	Oral, IV	gestational choriocarcinoma, choriocarcinoma and hydatidiform mole, BC, head, and neck cancer, LC (scaly and with small cells), NHL	Anaphylaxis	Acral erythema, rash, pruritis, urticaria, vasculitis, erythema multiformae, photosensitivity, stomatitis, psoriasis, pigmentation, SJS, TEN, alopecia	Bronchospasm, pulmonary infiltrates, hemolytic anemia, agranulocytosis, myelosuppression, hepatotoxicity
	Folate antagonists	Pemetrexed	IV	malignant pleural mesothelioma, NSCLC	-	Rash, pruritus, vasculitis, mucositis, stomatitis, TEN, alopecia	Neutropenia, thrombocytopenia, anemia, interstitial pneumonitis, dyspnea, mucositis
	Pyrimidine analogues	Capecitabine	oral	metastatic CRC	-	Acral erythema, erythema, exfoliative dermatitis, PPK, stomatitis, photosensitivity, hyperpigmentation, RRR, IRAK	Lymphopenia, thrombocytopenia, neutropenia, anemia
		Cytarabine	IV	acute nonlymphocyticleukemia, ALL, chronic myelocytic leukemia	Anaphylaxis	Urticaria, angioedema, acral erythema, pruritus, TEN, vasculitis, AGEP, NEH, MPR	Thrombocytopenia, leucopenia, fever, dyspnea, ARDS, hepatotoxicity, bleeding
		5′-Fluorouracil	IV	CRC, BC, GC, PC, liver, uterine, OC, bladder cancer	Anaphylaxis	Acral erythema, MPR, photosensitivity, stomatitis, contact dermatitis, ISR, alopecia	Myelosuppression, mucositis
		Gemcitabine	IV	NSCLC, PC, OC, BC, bladder cancer	-	Cutaneous: Pruritus, MPR, acral erythema, bullous dermatitis, vasculitis, stomatitis, SJS, TEN, RRR,	Fever, pneumonitis, leukopenia, neutropenia, anemia, thrombocytopenia
PLATINUM COMPOUNDS [17]	DNA cross-linkers	Carboplatin	IV	OC, LC, BC, head and neck, testicular, brain (children) cancers	Anaphylaxis	Rash, pruritus, urticaria, angioedema, erythema, edema	BMS, bronchospasm, dyspnea, peripheral neuropathy
		Cisplatin	IV	sarcomas, OC, lymphomas, LC, germ cell cancers	Anaphylaxis	flushing, rash, urticaria, pruritus	Bronchospasm, dyspnea, hemolytic anemia, renal toxicity
		Oxaliplatin	IV	Metastatic CRC, OC, GC	Anaphylaxis	Flushing, erythema, urticaria, angioedema, pruritus, rash, acralerythema, RRR	Fever, dyspnea, wheezing, types II and III hypersensitivity
MITOTIC INHIBITORS [3]	Vinca alkaloids	(a) Vinblastine (b) Vincristine (c) Vindesine (d) Vinorelbine	IV	(a) HL, NSCLC, head and neck, NHL, BC, Kaposi syndrome. (b) HL, WT, leukemia, Ewing sarcoma, rhabdomyosarcoma, neuroblastoma, nephroblastoma, embrionary child tumors, osteosarcoma. (c) Melanoma, LC, BC, leukemia. (d) BC, bone, NSCLC,	Anaphylaxis	Acral erythema, rash, phlebitis, cellulitis, stomatitis, nail lesions, alopecia, Raynaud’s phenomenon	Fever, bronchospasm, ARF, pulmonary edema, pleural effusion, interstitial pneumonitis
	Taxanes	Docetaxel	IV	OC, BC, LC, AIDS-related Kaposi sarcoma	-	Acral erythema, scleroderma-like, CLE, stomatitis, RRR, ISR, nail abnormalities, TEN	Anemia, neutropenia, leukopenia, bronchospasm, dyspnea, back pain
		Paclitaxel	IV	BC, NSCLC, metastatic hormone-resistant prostate cancer, GC, squamous cell of head and neck cancers	-	Acral erythema, ISR, erythema multiformae, RRR, AGEP-like, SIS, alopecia	Neutropenia, BMS, hypersens pneumonitis, dyspnea, back pain
		Cabazitaxel	IV	hormone-resistant metastatic prostate cancer	-	Rash	Myelosuppression, nausea, vomiting, constipation, peripheral -neuropathy, neuromuscular pain
TOPOISOMERASE INHIBITORS [8]	Topoisomerase I inhibitors	Irinotecan	IV	CRC, squamous cell carcinoma of the cervix	Anaphylaxis	Rash, alopecia	Neutropenia, anemia, dyspnea
	Topoisomerase II inhibitors	Daunorubicin	IV	AML, ALL, neuroblastoma	Anaphylaxis	Rash, urticaria, angioedema, hyperpigmentation	BMS, fever, cardiac toxicity
		Doxorubicin	IV	HL, hematologic, OC, BC, LC, bladder cancer, Kaposi’s	Anaphylaxis,	Rash, acral erythema, ISR, pruritus, urticaria, angioedema, NEH, RRR	Myelosuppression, bronchospasm, cardiotoxicity
		Mitoxantrone	IV	BC, AML, NHL, ALL	Anaphylaxis	Rash, ISR, purpura, nail discoloration, stomatitis, alopecia	Myelosuppression,
DISRUPTION OF PROTEIN SYNTHESIS [12]		L-Asparaginase	IV	ALL, AML	Anaphylaxis	Urticaria, angioedema, rash, pruritus, stomatitis, TEN	Laryngospasm, BMS, pancreatitis
MONOCLONAL ANTIBODY [15]		Rituximab	IV	follicular lymphoma stage III-IV, diffuse big B cell NHL, LLC	Anaphylaxis	Paraneoplastic pemphigus, lichenoid dermatitis, vesiculobullous dermatitis, SJS, TEN	Pulmonary events, renal toxicity, neutropenia, serum sickness, fever, lymphopenia, chills, asthenia
		Brentuximab vedotin	IV	HL, Systemic anaplastic large cell lymphoma, Cutaneous T-cell lymphoma	Anaphylaxis	Rash, pruritus, SJS, alopecia	Cytopenia, immunogenicity, URTI, pyrexia, nausea, vomiting, fatigue, cough
		Cetuximab	IV	CRC, Squamous cell cancer of the head and neck	Anaphylaxis	Acneiform rash, nail changes, xeroderma, paronychial inflammation, pruritus	Electrolyte imbalance, infection, headache, diarrhea
		Trastuzumab			Anaphylaxis/Angioedema	Rash, nail disorders, pruritus	Neutropenia, anemia, thrombocytopenia, pulmonary events, LVD, chills, fever, URTI, headache, cough, stomatitis, mucosal inflammation
SIGNAL TRANSDUCTION INHIBITORS [13]	Non-receptor tyrosine kinase inhibitors	Bosutinib	IV	Ph+CML	Anaphylaxis	Rash, pruritus	Neutron, anemia, edema, hepatotoxic, pneumonia, pyrexia, cough, renal toxicity, EFT
SIGNAL TRANSDUCTION INHIBITORS [13]	Receptor tyrosine kinase inhibitors	Lapatinib	IV	Metastatic BC	Anaphylaxis	Rash, HFSR, pruritus, xerosis, paronychia, nail disorders, alopecia	Cardiac toxicity, hepatotoxicity, ILD, diarrhea
HORMONES, HORMONE ANALOGS, AND HORMONE ANTAGONISTS [18]	Aromatase inhibitors	Exemestane	oral	BC in Postmenopausal women	Anaphylaxis	Rash, urticarial, pruritus, cutaneous vasculitis, erythema multiformae, AGEP, alopecia, dermatitis	Hot flushes, arthralgia, dyspnea, decreased bone density, EFT
	Aromatase inhibitors	Letrozole	oral	BC in Postmenopausal women	Anaphylaxis	Angioedema, rash, erythema multiformae, TEN, alopecia	Flushing, dyspnea, EFT, diaphoresis, arthralgia, hypertension, peripheral edema, decreased bone density
	Gonadotropin-releasing hormone analogs (GnRH agonists)	Goserelin	IV	Prostate cancer, BC	Anaphylaxis	Rash, itching, RPCS, acne, seborrhea, alopecia	Hot flushes, DIDF, anemia, osteoporosis, vaginitis
	Gonadotropin-releasing hormone analogs (GnRH agonists)	Leuprolide		Prostate cancer, BC	Anaphylaxis	Rash, injection site granuloma, pruritus, xerosis, ecchymosis, photosens, pigmentation	Hot fushes, DIDF, thrombo, anemia, peripheral edema

ACD = allergic contact dermatitis, AGEP = acute generalized exanthematous pustulosis, ALL = acute lymphocytic leukemia, AML = acute myeloid leukemia, ARDS = acute (adult) respiratory distress syndrome, ARF = acute respiratory failure, BC = breast cancer, BMS = bone marrow suppression, CLL = chronic lymphocytic leukemia, CML = chronic myeloid leukemia, CML = chronic myeloid leukemia, CRC = colorectal cancer, CTCL = cutaneous T cell lymphoma, DIDF = drug-induced disease fare (tumor fare effect), EFT = embryo-fetal toxicity, GC = gastric cancer, HER2 human epidermal growth factor receptor 2, also known as HER2/neu, ErbB2, CD340, p185 or EGFR2, HFSR = hand-foot skin reaction, HL = Hodgkin’s lymphoma, HVOD = hepatic veno-occlusive disease, ILD = interstitial lung disease, IRAK = inflammatory response in actinic keratosis, ISR = injection site reaction, IV = intra venous, LC = lung cancer, LVD = left ventricular dysfunction, MPR = maculopapular rash, MPR = maculopapular rash, NEH = neutrophilic eccrine hidradenitis, NHL = non-Hodgkin lymphoma, NSCLC = non-small-cell lung cancer, OC = ovarian cancer, PC = pancreatic cancer, Ph+ = Philadelphia chromosome-positive, PPK = palmar-plantar keratoderma, RPCS = relapsing polychondritis cutaneous symptoms, RRR = radiation recall reaction (dermatitis), SJS = Steven’s-Johnson syndrome, TEN = toxic epidermal necrolysis, URTI = upper respiratory tract infection, UTRT = urinary tract and renal toxicity, VEGFR2 vascular endothelial growth factor receptor 2, also known as KDR (kinase insert domain-containing receptor), WT = Wilms’ tumor.