1 Essentials of Medical Oncology



10.1055/b-0038-160292

1 Essentials of Medical Oncology

Vivek R. Sharma

Introduction


The purpose of this chapter is to give the reader an in-depth understanding of the overarching principles that guide the current practice of medical oncology and its role in the management of the cancer patient. It is not intended to provide details about individual drugs or the management of any one particular type of cancer but rather to serve as a general overview that complements the reviews on the roles of surgical and radiation oncology.


In the simplest of terms, the specialty of medical oncology involves the use of systemic therapy in the treatment of cancer. This would be the ideal way to treat the disease if we had highly effective and minimally toxic agents such as we do for example for treating various infectious diseases. However, that is presently not the case in oncology where most available agents, even though active, are often not curative. Further, most of these have significant toxicities that require them to be administered with substantial caution and close monitoring. The following sections will review the general principles of how they are used by themselves as well as in combination with other anti-cancer modalities to maximize therapeutic benefits and minimize toxicities.



Historical Background


The term “systemic therapy” implies administration of a chemical or biological agent in such a way that it enters the blood stream and distributes through the entire body to produce its therapeutic effect. Although this approach has been used in some form or fashion since ancient times, the modern era of chemotherapy began in the 1940s with the demonstration that nitrogen mustard, a derivative of mustard gas that was used as a chemical weapon during the first world war and was found to cause severe lymphoid and myeloid depletion in its victims, had therapeutic activity in lymphoma. 1 Subsequent advancement in the field was rather sporadic over the next several decades with more agents such as methotrexate being developed that showed impressive activity in hematological malignancies and even led to cure in choriocarcinoma. 2 However, optimism remained low as benefits were typically transient and toxicities were not trivial. A significant turning point came in the mid-1960s when Drs. Holland, Freireich, and Frei used a combination of chemotherapeutic agents to cure patients with leukemia and this strategy was subsequently used by other investigators to cure lymphomas and testicular cancer. 3 , 4 , 5 , 6 , 7 , 8 , 9 The number and types of available agents have since increased, but the idea of using combinations to achieve the best outcomes still remains the predominant therapeutic approach used by medical oncologists. In the 1990s, monoclonal antibodies were introduced for the treatment of cancer with rituximab for non-Hodgkin lymphoma and trastuzumab for breast cancer. 10 , 11 , 12 , 13 Several others have since been added for various cancers ( Table 1.1 ). Also, small molecule tyrosine kinase inhibitors were introduced in the late 1990s in the form of Bcr/Abl antagonist, imatinib mesylate for treatment of chronic myeloid leukemia. 14 , 15 This strategy has been subsequently applied to several other targets in various tumor types ( Table 1.2 ). Other novel approaches that appear promising include agents that modulate the immune system to target cancer cells. Among these are monoclonal antibodies that block the immune check points cytotoxic T-lymphocyte-as-sociated protein 4 (CTLA-4; Ipilimumab) or programmed death 1 (PD-1; Nivolumab, Pembrolizumab) on immune cells. They were initially tested and Food and Drug Association (FDA) approved for treatment of malignant melanoma but have since showed activity in several other tumor types. 16 , 17 Additional immunotherapeutic strategies include oncolytic viruses (Talimogene laherparepvec [T-VEC]) that disrupt cancer cells and trigger an immune response against them 18 and the use of adaptive immunity by way of genetically engineered T-cells (chimeric antigen receptor T cell [CART]). 19









































Table 1.1 Examples of therapeutic monoclonal antibodies in oncology

Monoclonal antibodies


Targets


Malignancies


• Trastuzumab


Her2 neu


Breast, gastric/esophageal


• Rituximab


CD20


Lymphoma, leukemia


• Bevacizumab


VEGF


Colon, lung (adeno), ovarian, cervical, GBM


• Cetuximab


EGFR


Colon, squamous cell head and neck


• Ipilumimab


CTLA-4


Melanoma


• Pembrolizumab


PD-1


Melanoma, NSCLC, MSI-H cancers, squamous cell head and neck, urothelial bladder cancer, Hodgkin’s disease


• Daratumumab


CD38


Multiple myeloma


Abbreviations: Her2, human epidermal growth factor receptor 2; VEGF, vascular endothelial growth factor; GBM, glioblastoma multiformae; EGFR, epidermal growth factor receptor; CTLA-4, cytotoxic T lymphocyte associated protein 4; PD-1, programmed cell death protein-1; NSCLC, non-small-cell lung cancer; MSI-H, microsatellite instability-high.





































Table 1.2 Examples of small molecule tyrosine kinase inhibitors (TKIs) in oncology

Small molecule TKIs


Targets


Malignancies where active


• Imatinib


Bcr-abl kinase


CML, GIST


• Erlotinib


EGFR kinase


NSCLC, pancreatic cancer


• Crizotinib


ALK


ALK positive NSCLC


• Sorafenib


Multi-targeted


HCC, renal cell


• Sunitinib


Multi-targeted


Renal cell, GIST, pNET


• Regorafenib


Multi-targeted


Colon, GIST, HCC


Abbreviations: Bcr-abl, Breakpoint cluster region on chromosome 22-Abelson on chromosome 9; EGFR, epidermal growth factor receptor; ALK, anaplastic lymphoma kinase; CML, chronic myelogenous leukemia; GIST, gastrointestinal stromal tumor; HCC, hepatocellular cancer; pNET, pancreatic neuroendocrine cancer.


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May 21, 2020 | Posted by in ONCOLOGY | Comments Off on 1 Essentials of Medical Oncology
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