Traditional Cancer Therapies and Perioperative Implications

Introduction

Preoperative cancer therapies such as chemotherapy and radiation can have direct implications on perioperative management during cancer surgery. Chemotherapy is intended to prevent proliferation of malignant cells (cytostatic) and cause death of tumor cells (cytotoxic). It can be given at various stages during cancer treatment, including before surgery (neoadjuvant), after surgical resection (adjuvant), or as palliative therapy to improve quality of life. Chemotherapy is usually administered in cycles every 2–3 weeks, which allows patients to recover from its toxic effects. In this chapter, we focus on reviewing traditional chemotherapeutic agents, their toxicities on organ systems, and how to mitigate these effects perioperatively. Most commonly, patients experience toxicities related to cardiac, pulmonary, gastrointestinal, and hematologic systems. A full discussion of the perioperative implications of the numerous classes of chemotherapy is beyond the scope of this chapter. We have attempted to summarize the perioperative implications of chemotherapy in Table 4.1 . Radiation therapy has fewer systemic perioperative concerns, but patients do frequently present with late complications from therapy that may alter perioperative evaluation and management.

Table 4.1

Chemotherapy and Perioperative Concerns

Class	Agents	Common Perioperative Concerns
Alkylating Agents
Nitrosoureas	CarmustineLomustine	Pulmonary fibrosis
Methylating agents	Procarbazine	EdemaTachycardia
	Dacarbazine	Hepatic necrosis and occlusionHepatic vein thrombosis
	Temozolomide	Seizure and gait abnormalityPeripheral edema
Platinums	CisplatinCarboplatinOxaliplatin	Acute renal tubular necrosisMagnesium wastingPeripheral sensory neuropathyParesthesiasOtotoxicity
Nitrogen mustards	CyclophosphamideIfosfamide	PericarditisPericardial effusionsPulmonary fibrosisHemorrhagic cystitisWater retentionAnemia
	Melphalan	SIADH
	Chlorambucil	SIADHSeizures
Antimetabolites
Anthracyclines	DoxorubicinDaunorubicinEpirubicinIdarubicinMitoxantroneValrubicin	CardiomyopathyECG changes
Antitumor antibiotics:Natural product	BleomycinMitomycin C	Pulmonary fibrosisPneumonitisPulmonary hypertension
Pyrimidine analogue	CapecitabineCytarabine (Ara-C)Fluorouracil	Myocardial ischemia/infarctionCoronary vasospasm
	Gemcitabine	EdemaProteinuria
Purine analogue	Thioguanine	Hepatotoxicity
	Pentostatin	Pulmonary toxicityDeep vein thrombophlebitisChest painEdemaAV blockArrhythmiaHypo- and hypertension
	Cladribine	ThrombosisTachycardiaAcute renal failureTumor lysis syndrome
	Fludarabine	Cerebrovascular accident/transient ischemic attackAnginaThrombosis
		ArrhythmiaHeart failureAcute renal failureTumor lysis syndrome
	Mercaptopurine	Intrahepatic cholestasis and focal centrilobular necrosis
Folate antagonist	Methotrexate	Elevated liver enzymesPulmonary edemaPleural effusionsEncephalopathyMeningismusMyelosuppression
Substituted urea	Hydroxyurea	SeizureEdema
Microtubule Assembly Inhibitors
Taxanes	PaclitaxelDocetaxel	Peripheral neuropathyBradycardiaAutonomic dysfunctionCardiomyopathy (combination with anthracyclines)
Alkaloids	Vinblastine	HypertensionAnginaCerebrovascular accidentCoronary ischemiaECG abnormalitiesRaynaud’s phenomenonSIADHGI bleed
	Vincristine	ParesthesiasRecurrent laryngeal nerve palsyAutonomic dysfunctionOrthostasisHypo- and hypertensionSIADH
Biologic Agents
Monoclonal antibody	Alemtuzumab	Dysrhythmia/tachycardia/SVTHypotension and hypertension
	Bevacizumab	Pulmonary bleedingHypertensionThromboembolic events
	Cetuximab	Cardiopulmonary arrest
	Rituximab	Tumor lysis syndromeElectrolyte abnormality
	TrastuzumabPertuzumabOfatumumab	CardiomyopathyThrombus formationPulmonary toxicityTachycardiaHypertension
	Daclizumab	Chest painHyper- and hypotensionThrombosis
	Ibritumomab	Peripheral edema
	Palivizumab	Arrhythmia
	Muromonab-CD3	TachycardiaHyper- and hypotension
Immune Checkpoint Inhibitors
	Ipilimumab (Yervoy)Nivolumab (Opdivo)Pembrolizumab (Keytruda)Atezolizumab (Tecentriq)	Immune-mediated adverse effects may affect numerous organ systems. Adverse effects may present as myocarditis, dermatitis, nephritis, encephalitis, pneumonitis, thyroiditis, hepatitis, hypophysitis, colitis, arthritidis, etc.
	Avelumab (Bavencio)Durvalumab (Imfinzi)Cemiplimab (Libtayo)	A high clinical suspicion for late immune-mediated side effects needs to be present for patients with prior treatment of immune checkpoint inhibitors
Biological Response Modulators
Interleukins	AldesleukinDenileukin Diftitox	Capillary leak syndromePeripheral edemaHypotensionECG changes
Interferon	Interferon Alfa-2bInterferon Alfacon-1	ArrhythmiaChest painPulmonary pneumonitisIschemic disordersHyperthyroidismHypothyroidism
	Peginterferon alfa-2aPeginterferon alfa-2b	Pulmonary infiltratesIschemic disordersHyperthyroidismHypothyroidism
Vascular Endothelial Growth Factor (VEGF) Inhibitors
Tyrosine kinase inhibitors	Imatinib	EdemaLeft ventricular dysfunction
	Sorafenib	Cardiac ischemia and infarctionHypertensionThromboembolismCardiac ischemia and infarctionThromboembolism
	Sunitinib	Adrenal insufficiencyPulmonary hemorrhageHypertension
		HypothyroidismCardiomyopathyQT prolongationTorsade de pointes
	Dasatinib	Fluid retentionCardiomyopathyQT prolongationPulmonary hemorrhagePlatelet dysfunction
	Nilotinib	QT prolongationHypertensionPeripheral edema
Epidermal Growth Factor Receptor (EGFR) Inhibitors
	Erlotinib	Deep venous thrombosisArrhythmiaPulmonary toxicityCerebrovascular accidents
		Myocardial ischemiaSyncopeEdema
	Lapatinib	CardiomyopathyPulmonary toxicityQT prolongation
	Panitumumab	Pulmonary fibrosisPeripheral edema
Angiogenesis inhibitors
Immunomodulators	Thalidomide	ThromboembolismEdemaBradycardia
	Lenalidomide	Thromboembolism
Enzymes
	Asparaginase	ThrombosisGlucose intoleranceCoagulopathy
Miscellaneous
Topoisomerase I inhibitor	IrinotecanTopotecanRubitecan	NeutropeniaDiarrheaCholinergic syndrome
Epipodophyllotoxin topoisomerase II inhibitor	Etoposide	NeutropeniaStevens-Johnson syndromeToxic epidermal necrolysisMyocardial infarctionCongestive heart failure
Selective Estrogen Receptor Modulators
	Tamoxifen	Thromboembolism
	Toremifene
Aromatase inhibitors
	AnastrozoleLetrozole	Perioperative implicationsUnknown/limited data
	Exemestane
mTor inhibitors
	SirolimusEverolimusTemsirolimus	DyslipidemiaHypertensionRenal dysfunctionHyperglycemia/diabetesInterstitial lung disease
Hedgehog Pathway Inhibitors
	Vismodegib	Perioperative implicationsUnknown/limited data
Androgen Targets
	Abiraterone	HypertensionHypertriglyceridemiaHyperglycemiaHypernatremiaHypokalemiaQT prolongation
	Bicalutamide	HepatoxicityHyperglycemiaProlonged QT interval
Histone Deacetylase Targets
	Romidepsin	Prolonged QT interval
	Vorinostat	HyperglycemiaProlonged QT interval
Folate Targets
	Pralatrexate	Perioperative implicationsUnknown/limited data
Retinoic Acid Receptor Targets
	IsotretinoinAcitretin	Hypertriglyceridemia
Proteasome Targets
	BortezomibCarfilzomib	Peripheral neuropathyHeart failureHepatoxicityCardiac ischemia
Immunomodulatory Agents
	ThalidomideLenalidomide	Thromboembolism