Part III Management of the Side Effects of Chemotherapy and Radiotherapy

Chapter 2

Drugs and Potential Drugs as Chemoprotectors 

In this chapter, we will discuss drugs and potential drugs (often referred to as agents) that may be used before chemotherapy to reduce the side effects. These drugs/agents are often referred to as chemoprotectors. Examples of chemoprotectors are listed below based on the individual targets to be protected.

1. Drugs to Increase White Blood Cell Count

Filgrastim

Filgrastim is a 175-amino acid human granulocyte colony-stimulating factor (G-CSF) manufactured by recombinant DNA technology in E Coli. It is a glyprotein naturally produced by a number of different tissues to stimulate the bone marrow cells to produce granulocytes and release them into the blood.

Filgrastim is used to stimulate the proliferation and differentiation of neutrophils, which are the most abundant type of WBCs. It is marketed as Neupogen® by Amgen, as Religrast® by Reliance Biopharmaceuticals, and as ShilgrastTM by Raichem Lifesciences.

Sargramostim

Sargramostim is a WBC stimulant sold as Leukine® by Genzyme. It is a human granulocyte macrophage colony stimulating factor (GM-CSF) produced by recombinant DNA technology in a yeast, S. cerevisiae. Sargramostim is a glycoprotein having 127 amino acids. Its amino acid sequence is different from the natural human GM-CSF by a substitution of leucine at position 23. It was originally approved by the FDA in March, 1991 for use following autologous bone marrow transplantation (BMT) and was approved in December 1991 to prevent death following BMT engraftment delay or failure. In September of 1995, it was subsequently licensed to shorten the time for neutrophil recovery to prevent early death from life- threatening infections following chemotherapy for older patients suffering from acute myelogenous leukemia (AML). 

© Jiajiu Shaw, 2023

Disclaimer: This blog is written solely for informational purposes. It does not constitute the practice of any medical, nursing or other medical professional health care advice, diagnosis, or treatment. All contents posted are extracted from the book, "SIDE EFFECTS OF CHEMOTHERAPY AND RADIOTHERAPY", prepared by Dr. Jiajiu Shaw, Dr. Frederick Valeriote, and Dr. Ben Chen. 

Radiotherapy and Its Side Effects: Chapter 1 - Introduction

PART II

Chapter 1

Introduction (cont'd)

Radiotherapy has been used for both curative and adjuvant cancer treatment for many years. Adjuvant therapy refers to auxiliary/additional treatment for cancer; adjuvant radiotherapy is usually given after surgery or in conjunction with chemotherapy when a potential risk of relapse remains. Radiotherapy can also be given before surgery to reduce the mass of tumor to be removed.

Roughly speaking, 60% of all cancer patients receive radiotherapy, thus, radiotherapy might not be necessary for all cancer cases. For example, according to a scientific report in the New England Journal of Medicine, it was indicated that children with the most common form of leukemia can safely forego radiation therapy if they are treated with chemotherapy regimens tailored to their individual needs. The conclusion was based on a clinical trial involving 498 patients with acute lymphoblastic leukemia.  Nearly 94 percent of the patients were still alive 5 years after treatment, a result that compares favorably with other treatment studies.

An overly simplified schematic representation of how radiation works is shown in Fig. 2.1. Basically, radiation therapy works by damaging the DNA of cancer cells and hampering these cells from replicating. The damage to cancer cells is caused by radiation, which directly or indirectly breaks up the DNA chain. The indirect damage comes from free radicals including hydroxyl radical (HO^·), superoxide  (O₂^-), hydrogen peroxide (H₂O₂), peroxyl (ROO^·) and alkoxyl (RO^·) radicals, collectively called reactive oxygen species (ROS).  

Fig. 2.1   Schematic representation of how radiation works

© Jiajiu Shaw, 2020

Disclaimer: This blog is written solely for informational purposes. It does not constitute the practice of any medical, nursing or other medical professional health care advice, diagnosis, or treatment. All contents posted are extracted from the book, "SIDE EFFECTS OF CHEMOTHERAPY AND RADIOTHERAPY", prepared by Dr. Jiajiu Shaw, Dr. Frederick Valeriote, and Dr. Ben Chen. 

Chemotherapy and Its Side Effects: Chapter 2 - Kinase Modulators (cont'd)

E.1. Imatinib mesylate (sold as Gleevec® by Novartis)

Fig. 1.12

Imatinib (Fig. 1.12) was first approved by the FDA in 2001 and sold as Gleevec^®. It works by specifically targeting, and turning off constitutively active tyrosine kinases (Bcr-abl) which help cancer cells grow and multiply. Bcr-abl kinase is a hybrid product of a chimeric Bcr-abl oncogene caused by translocation between chromosomes 9 and 22. The tyrosine kinases cause several cancers including Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) and gastrointestinal stromal tumor (GIST). Gleevac comes in tablet form. When given by oral administration, the active ingredient, imatinib, is rapidly absorbed.

Potential side effects of Gleevec include fluid retention, rash, nausea & vomiting, muscle cramps, and diarrhea. 

© Jiajiu Shaw, 2019

Disclaimer: This blog is written solely for informational purposes. It does not constitute the practice of any medical, nursing or other medical professional health care advice, diagnosis, or treatment. All contents posted are extracted from the book, "SIDE EFFECTS OF CHEMOTHERAPY AND RADIOTHERAPY", prepared by Dr. Jiajiu Shaw, Dr. Frederick Valeriote, and Dr. Ben Chen.