Handbook of Cancer Treatment-Related Symptoms and Toxicities E-Book

Vamsidhar Velcheti, Salman R Punekar

• Publisher: Elsevier
• Year: 2021
• ISBN:
  9780323672993
• Topic: Medicine
• Subtopic: Hematology

Early recognition and management of adverse effects of cancer treatments are essential for optimal care of patients with cancer, and drastically different approaches are required for different physiologic reactions. Handbook of Cancer Treatment-Related Symptoms and Toxicities is a focused, one-stop resource that enables clinicians to quickly find up-to-date, reliable information needed at the point of care. The high-yield approach prioritizes the most common toxicities associated with cancer treatment, and concise, templated chapters offer fast access to information needed in day-to-day practice.

• Presents a user-friendly overview of cancer treatment-related symptoms and toxicities management in a practical, easy-to-use format, allowing you to quickly find information in one convenient, concise resource.
• Covers systemic and radiation therapies, including chemotherapy, immunotherapy, targeted therapies, and radiation therapy, detailing symptoms of each toxicity to confirm your diagnosis.
• Overviews pharmacologic and non-pharmacologic approaches to symptom management.
• Offers recommendations for mitigating toxicities in high-risk patients.
• Discusses key topics such as management of infusion reactions, when the need for biopsy is warranted, and the unique challenges posed by novel immunotherapies.

PART 1

Cytotoxic Chemotherapy

CHAPTER 1

Mechanisms of Cancer-Directed Therapies

Salman R. Punekar, MD

Mechanisms of Cancer-Directed Therapies

Cancer has been prevalent for centuries and humans have been concerned with the treatment of cancer for a seemingly equal time. Breast cancer was first described thousands of years ago and was first reported to be treated with surgery in 500 BCE. In the 18th and 19th centuries, surgical resection for the treatment of cancer started to gain popularity, but it was only in the early 1900s that chemotherapy entered the picture.¹ It was post-World War II that chemotherapy began to become widely used with cures of leukemia and lymphoma described in the 1960s.² While oncologists became the purveyors of chemotherapy, they equally began managing complications of these same treatments. Thus, a mechanistic understanding is essential to the prediction and treatment of complications stemming from cancer-directed therapies.

CATEGORIES OF CANCER-DIRECTED THERAPY

• ▪ Cytotoxic chemotherapy: The term chemotherapy arises from the concept of treating disease with chemicals. Traditional chemotherapy was developed in the early 1900s and is still a part of the treatment program for most cancers. Some common types of chemotherapy include pyrimidine analogs, purine analogs, anthracyclines, antifolates, alkylating agents, platinum derivatives, DNA topoisomerase inhibitors, taxanes, vinca alkaloids, hypomethylating agents, and proteasome inhibitors, among others.
• ▪ Targeted therapy: Targeted therapies come in various forms but are generally monoclonal antibodies or small molecules that interact with a specific molecule known to be implicated in cancer growth. Some examples include imatinib targeting BCR-ABL, bevacizumab targeting VEGF, trastuzumab targeting HER2, and erlotinib targeting EGFR, among an ever-increasing number of drugs.
• ▪ Immunotherapy: Immunotherapy is a relatively new form of cancer-directed therapy, encompassing vaccine, cellular, cytokine, anti-CTLA-4, and anti-PD-1 therapies. Examples of the most commonly used therapies are pembrolizumab, ipilimumab, and nivolumab.
• ▪ Radiation therapy: Radiation therapy can be divided into two types, based on the source of radiation. External beam radiation refers to radiation in which the source comes from outside the patient. Internal beam radiation, also known as brachytherapy, refers to radiation in which the source is placed next to, or within, a tumor. Complications from radiation therapy arise from radiation exposure to non-tumor cells and are based on the type and location of cells that are affected.

References

1. Mukherjee S. The Emperor of All Maladies: A Biography of Cancer. 1 ed. New York: Scribner; 2010.

2. DeVita VT, Chu E. A History of Cancer Chemotherapy. Cancer Res. 2008;68(21):8643–8653.

CHAPTER 2

Neutropenic Complications of Chemotherapy

Alankrita Taneja, MBBS
Dale Shepard, MD, PhD

Abstract

Neutropenia is a common complication of chemotherapy, and carries significant morbidity and mortality. Neutropenia can significanty increase the risk of infection in patients in whom infection may not be obvious. In this chapter, we discuss causes of neutropenia in cancer patients, strategies for risk assessment, as well as the evaluation and management of chemotherapy-induced neutropenia.

Keywords

Neutropenia; Neutropenic fever; Granulocytopenia; chemotherapy complications

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 important to understand normal physiology in order to understand neutropenia and its complications. Most neutrophils reside in the bone marrow¹ in mitotic (myeloblasts, promyelocytes, myelocytes) and postmitotic (metamyelocytes, bands, and then neutrophils) stages. Of the neutrophils in the circulation, an equal proportion make up the marginal and the nonmarginal pool.² From the circulation, neutrophils enter tissue as a result of proinflammatory trafficking cytokines. Neutropenia is a reduction in the nonmarginal pool of neutrophils which constitute only 4% to 5% of total neutrophil stores.

Neutropenia is defined as an absolute neutrophil count (ANC) of less than 1500 cells/µL; ANC of less than 1000 cells/µL is considered moderate neutropenia and ANC of less than 500 cells/µL is considered severe neutropenia. The risk of infection is greatest with severe neutropenia.³

Etiology of Neutropenia

• ▪ Neutropenia is a common complication seen in various malignant conditions. There are many contributing factors that should be considered in patients with malignancy. Table 2.1⁴ describes causes of neutropenia commonly seen in patients with malignancy. Although neutropenia is the most common dose limiting toxicity (DLT) of chemotherapy,⁵ it is important to consider the differential diagnosis to determine the appropriate management for each patient.
• ▪ There are several ways in which chemotherapy predisposes to infections. While neutropenia is an important etiology, chemotherapy can also impair physical barriers created by mucosal surfaces, the first line of defense against infections. Classic signs of inflammation including dolor (pain), calor (heat), rubor (redness), tumor (swelling), and functio laesa (loss of function) may be dampened in such patients due to blunting of the function of neutrophils. Thus increasing the chance of infections to be missed. Fever is usually the only sign of infection in neutropenic infections and thus warrants special vigilance.⁴

TABLE 2.1

Causes of Neutropenia in Cancer Patients⁴

Causes of Neutropenia in Malignancy	Mechanism
Chemotherapy (the chemotherapy regimen remains the strongest determinant in the likelihood of developing neutropenia)	Myelosuppressive effects due to cytotoxicity
Chronic lymphoproliferative disorders – natural killer cell lymphomas (large granular lymphocytic leukemia), hairy cell leukemia, and chronic lymphocytic leukemia (CLL)	Bone marrow infiltration
Radiation	Cytotoxic Effects
Autoimmune conditions: Systemic lupus erythematosus (SLE), aplastic anemia, Crohn's disease	Presence of antineutrophil antibodies
Rheumatoid arthritis (Felty's syndrome)	Hypersplenism
Granulomatous infections	Bone marrow infiltration
Viral infections (e.g., CMV, EBV, HIV)	Bone marrow suppression
Parasitic infections (e.g., malaria)	Hypersplenism, multifactorial
Bacterial infections (e.g., typhoid, tuberculosis)	Multifactorial
Hemophagocytic lymphohistiocytosis (HLH)	Infiltration of bone marrow, hypersplenism
Antibiotic-induced isolated neutropenia (e.g., quinidine, hydralaz...