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Neurological Toxicities of Immunotherapy

Introduction Cancer immunotherapy has a rich history. In the late 19th century, William Coley treated sarcoma patients with intratumoral bacteria and bacterial products and demonstrated tumor shrinkage. Over the years, we have added significantly to the “immunological armament” against cancer. In the past two decades, there has been an explosion of immunotherapies which have brought this field to the forefront of oncology. These new agents activate…

Gastrointestinal Toxicities of Immunotherapy

Introduction Novel agents have revolutionized the treatment of cancer, resulting in many benefits for patients. These same agents, however, have been associated with new toxicity profiles compared with traditional chemotherapy. Most of these adverse events have been classified as mild or moderate, but unfortunately, severe and life-threatening complications also occur. This section will focus specifically on immunotherapy and subsequent gastrointestinal toxicity. The various approaches that will…

Endocrine Toxicities of Immunotherapy

Introduction In the past two decades, the field of cancer immunotherapy evolved from a niche specialty to the frontlines of the fight against cancer. Unlike chemotherapy, immunotherapy unleashes the body’s inherent immune system by boosting it and “releasing its breaks.” Although we have come far, immunotherapy remains a crude tool, and as collateral damage, we have a new set of toxicities which are labeled as immune-related…

Mechanisms of Immune-Related Adverse Events

Introduction ■ The origins of immunotherapy can be traced back to the early 1900s when Paul Ehrlich postulated that the host immune system plays a role in the early recognition and elimination of malignant cells. Over the next century, many other researchers built upon this notion. Theories of immunosurveillance , and cancer immunoediting were conceptualized, to help explain the complex interplay between the immune system and…

Cardiovascular Toxicities of Targeted Therapy

Introduction Cardiotoxicity is one of the worrisome side effects of cancer-directed therapy. Cardiac adverse events can range from mild to severe and vary between classes of targeted agents. Some relevant cardiac adverse events include electrocardiogram (ECG) changes, QT prolongation, hypertension, arrhythmias, pericardial disease, and heart failure. Cardiac toxicities can limit the use of these drugs and warrant their discontinuation. Preexisting comorbidities and cardiac conditions can add…

Dermatological Toxicities of Targeted Therapy

Introduction Targeted therapies are a rapidly expanding group of anticancer drugs, which promise to provide better tolerated and higher efficacy medications compared with conventional systemic chemotherapy. Inhibition of novel pathways or molecules brings about some unexpected and unforeseen adverse effects which are similar, yet distinct to those seen with chemotherapy. Cutaneous toxicity is the most common adverse drug reaction seen with targeted therapy. It ranges from…

Pulmonary Toxicities of Targeted Therapy

Introduction Prior to the 1990s, cytotoxic chemotherapy was used uniformly for all malignancies. This resulted in heterogeneous responses even within a specific tumor type. As insight was gained about the role of driver mutations (key alterations in the oncogenic addiction pathways of malignant cells), the concept of targeted therapies was born. By inhibiting driver pathways for carcinogenesis, these targeted agents were successful in managing cancers that…

Gastrointestinal Toxicities of Targeted Therapy

Introduction Targeted therapies are a category of drugs that inhibit cancer by interfering with specific molecules involved in the growth, progression, and spread of malignant cells. Targeted therapies act on specific molecular targets, whereas most standard chemotherapies act on many rapidly dividing normal and cancer cells. Many different targeted therapies have been approved by the US Food and Drug Administration (FDA) to treat specific types of…

Mechanisms of Toxicities Associated With Targeted Therapy

Introduction Over the last several years, molecularly targeted therapy has emerged as a new generation of cancer treatment and has been integrated into treatment protocols of many hematologic and solid tumors, either as monotherapy or in combination with chemotherapy. In general, targeted therapies include monoclonal antibodies and small molecule inhibitors that specifically affect the activity of genes or proteins mediating carcinogenesis. As described by Hanahan and…

Cancer Treatment Infusion Reactions

Introduction Cancer treatments have the potential to cause infusion reactions (IRs). It is important to manage IRs because they may cause treatment disruption and require costly medical interventions. Both cytotoxic and biological agents cause IRs. In general, IRs can be anaphylactic or anaphylactoid. ■ Anaphylactic IRs: Anaphylactic IRs are allergic in nature and are usually mediated by immunoglobulin E (IgE). Clinical symptoms do not vary widely…

Cardiovascular Toxicities of Chemotherapy

Introduction Cardiotoxic effects of chemotherapy are challenging in nature, since myocardial tissue possesses limited regenerative capacity, which renders the heart susceptible to transient and permanent side effects of chemotherapy agents. Furthermore, with increasing incidence of cardiovascular disease in the general population and improvement in survival of cancer patients as a result of marked advancement in cancer therapy, chemotherapy-induced cardiotoxicity is becoming a more significant issue for…

Dermatological Toxicities of Chemotherapy

Introduction Chemotherapy can affect skin in various ways, and several chemotherapeutic agents have been linked to distinctive cutaneous side effects. Although these side effects are rarely life-threatening, they can cause considerable distress and discomfort to patients (alopecia, hyperpigmentation), negatively impacting their quality of life and sometimes leading to interruptions of treatment. Occasionally, cutaneous reactions may be associated with more serious systemic toxicity. Characteristics of these adverse…

Pulmonary Toxicities of Chemotherapy

Introduction Respiratory insufficiency in patients receiving systemic chemotherapy often is a diagnostic dilemma for clinicians. Patients receiving chemotherapy are frequently immunosuppressed and may have concurrent bone marrow suppression, or pulmonary involvement from underlying malignancy, making the differential diagnosis of respiratory failure quite broad. It is imperative that common etiologies such as respiratory infections, congestive heart failure, venous thromboembolism, alveolar hemorrhage, radiation-induced lung injury, and toxicities from…

Neurological Complications of Chemotherapy

Introduction Chemotherapy-related neurotoxicity is a frequently observed side effect that has become more prevalent with the increasing number of long-term cancer survivors. These toxicities can be peripheral or central and can range from minor cognitive issues to encephalopathy or dementia. Toxicities are often dose-limiting, resulting in dose reduction or treatment discontinuation, potentially compromising the therapeutic efficacy. This chapter will discuss the incidence, mechanism, symptoms, and management…

Gastrointestinal Complications of Chemotherapy

Introduction Gastrointestinal (GI) toxicities are common side effects of most chemotherapy agents. Their effect on rapidly dividing GI tract cells can lead to mucosal inflammation, ulceration, and perforation. The most common GI toxicities include oral mucositis (see Chapter 5 ), dysphagia, odynophagia, esophagitis, gastritis, nausea and vomiting, enterocolitis, diarrhea, constipation, and hepatotoxicity. Other less common manifestations include GI hemorrhage, bowel perforation, pancreatitis, malabsorption, and infections of…

Oral Mucositis

Introduction ■ Mucositis is defined as inflammation of the mucous membranes lining the alimentary tract, causing mucosal injury. Mucositis can occur in response to systemic chemotherapy or other etiologies (e.g., infection, radiation). Mucositis generally begins approximately 3 to 4 days following administration of chemotherapy. , Mucosal injury beyond the oropharynx is discussed in Chapter 6. ■ Initial stages of oral mucositis are generally mild, with notable…

Cancer Treatment-Related Thrombocytopenia

Introduction ■ A multitude of cancer treatments are known to cause thrombocytopenia (TCP), termed treatment-related thrombocytopenia. Chemotherapy-induced thrombocytopenia (CIT) is a term that refers specifically to thrombocytopenia caused by chemotherapy drugs. Notably, many nonchemotherapy cancer treatments may also cause thrombocytopenia. ■ The normal platelet range is 150,000 to 450,000 The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) defines TCP according to grade.…

Chemotherapy-Induced Anemia

Introduction ■ Anemia is caused by the deficiency of red blood cells or hemoglobin, resulting in a reduction in the oxygen-carrying capacity of blood and is commonly associated with cancer-directed therapies. Chemotherapy, radiotherapy, and cancer-related surgery can all contribute to anemia. Despite being common, anemia associated with chemotherapy (CIA) is often underreported and is often only documented when severe, necessitating transfusion. There are several reasons for…

Neutropenic Complications of Chemotherapy

Introduction ■ Neutrophils, eosinophils, and basophils are a subset of white blood cells characterized by the presence of granules and collectively referred to as granulocytes. Granulocytopenia is a decrease in the absolute count of these three cell lines while neutropenia is a decrease in only the absolute neutrophil count (ANC). However, for practical purposes the terms granulocytopenia and neutropenia are often used interchangeably. ■ It is…