The content of this module is mirrored to the objectives listed by the 2015 Canadian Oncology Goals and Objectives for Medical Students (by the Canadian Oncology Group). After completing this module, students should be able to:
Traditional cancer chemotherapy is systemic drug therapy used to kill cancer cells(1) by causing lethal cytotoxicity or apoptosis (2). The various classes of chemotherapy generally work by attacking DNA, interfering with cell division or by interfering with metabolism essential for cell replication (2). As most traditional chemotherapies target rapidly dividing cells, they are not specific for just tumour cells, and consequently normal dividing cells can also be affected. Targeted therapies rather, allow for more precise neoplastic cell killing by targeting specific growth factors and receptors, downstream signalling molecules, tumor angiogenesis, as well as enhancing immune recognition of cancer cells(3).
Traditional systemic chemotherapies can be classified as cell-cycle specific, or cell cycle non specific. Cell cycle specific drugs are most effective against rapidly replicating cells whereas cell cycle non specific (CCNS) drugs can also target cells in the resting phase (G0) (4).
Chemotherapy can be indicated in different clinical settings:
Chemotherapy is generally prescribed by a medical oncologist who will take into account patient, tumour and treatment factors (refer to cancer management module).
With respect to patient factors oncologists will consider the patient’s age, other medical conditions, patient supports and patient preference. Tumour factors include the responsiveness of the tumour to chemotherapy and the stage of the tumour. Treatment factors include the morbidities associated with differing treatments.
Chemotherapy can consist of single or multiple drugs used in combination to treat cancer. Traditional chemotherapies are not targeted and generally affect the cell cycle and thus have effects on both normal tissues and cancer. Cells of the gastrointestinal tract, bone marrow, and hair matrix are particularly affected as they are cells that are normally rapidly dividing. This is an important concept with respect to the common toxicities of traditional chemotherapies.
The dosing of agents is typically based off the patient’s body surface area. As chemotherapies have significant side effects and may not kill all cancer cells in one treatment, it is commonly given in multiple cycles to kill as many cancer cells as possible and allow for recovery between cycles. Rest periods between cycles may last days to weeks depending on the regimen. The length of treatment is dependent on the type of cancer and the goals of therapy. Generally, regimens are shorter when there is curative intent and can be longer when the goal is palliative chemotherapy to control symptoms(6).
The main classes of traditional chemotherapy agents are the antimetabolites, antitumor antibiotics, alkylating agents, microtubule inhibitors, platinum agents, and the topoisomerase inhibitors.
Look at the “Specifics of Systemic Cancer Treatment module” for more detail on the various classes and types of chemotherapy.
In contrast to traditional chemotherapies, targeted and hormonal agents act in a more specific fashion. Generally they are better tolerated and therapy may be given for longer periods (6). Targeted therapies include the biologics and small molecule agents directed against specific oncogenic pathways.
Biologic therapies are usually monoclonal antibodies against cell surface (ie. growth factor receptors) or circulating antigens (ie. receptor ligands). Immunotherapy is a rapidly evolving area of cancer treatment which enables the body’s own immune system to better recognize and eradicate cancer cells.
As the cellular pathways in cancer are better understood, various small molecule agents have been developed to target cancer cells. Small molecule agents can enter cells and interfere with intracellular molecular targets – often kinases involved in the oncogenic process(3). Many small molecule agents are tyrosine kinase inhibitors which are involved in cancer pathways. A notable example is imatinib which revolutionized the treatment of chronic myeloid leukemia.
Hormonal agents are useful for hormone dependent cancers of the breast and prostate. Estrogen receptor positive breast cancers can be treated with selective estrogen receptor modulators and aromatase inhibitors.
Prostate cells are responsive to androgens for growth and therefore advanced prostate cancer can be treated with androgen deprivation therapy (ADT). ADT can be accomplished with GnRH (LHRH) agonists or antagonists.
Look at the “Specifics of Systemic Cancer Treatment module” for more details and examples of targeted and hormonal treatments.
While the various systemic cytotoxic agents have their own unique side effect profiles (see the specific module again) there are some common side effects associated with most systemic chemotherapies. Chemotherapy induced nausea and vomiting (CINV) may affect 70 to 80% of patients treated and can present in three main ways: acute (within a few hours of chemo), delayed (more than 24 hours after), and anticipatory (before treatment due to a conditioned response from previous CINV)(7,8). The management of CINV is dependent on the emetogenic potential of the agent which may be classified as high (>90%), moderate (30-90%), low (10-30%), or minimal (<10%)(8).
Myelosuppression is a side effect of many traditional chemotherapeutic agents and can lead to neutropenia. Neutropenia is usually defined as an absolute neutrophil count below 1 × 10^9/L. Neutropenic patients are unable to mount robust inflammatory responses. As a result, fever may be the only sign of infection in a patient. Furthermore, in addition to the effects on the bone marrow, systemic chemotherapies degrade the integrity of the GI mucosa which can lead to invasive infections by bacteria or fungi. Neutropenia accompanied by a fever (single oral temperature >38.3 °C or >38 °C for 1 hour) is known as febrile neutropenia. Febrile neutropenia can be life threatening and lead to sepsis, acute respiratory distress syndrome, or shock and requires immediate medical attention(9).
For a summary of common chemotherapy side effects see the table below:
Use your mouse to click through the slides and answer each question in the text box provided.
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