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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:

  1. Demonstrate an understanding of the general principles of chemotherapy in the treatment of cancer.
  2. List Factors that would make a cancer patient a good candidate for chemotherapy.
  3. Know the general differences between traditional chemotherapy and targeted biological therapy
  4. List common acute and chronic toxicities of chemotherapy (eg. alopecia, nausea, vomiting, neutropenia, mucositis, weight loss, neuropathy, secondary cancers), as well as potential life threatening toxicities (eg. febrile neutropenia)

General Principles of Chemotherapy

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: 

  1. primary chemotherapy used as induction of remission for disseminated disease
  2. neo-adjuvant to treat/shrink the cancer before surgery and/or radiation
  3. adjuvant given after surgery and/or radiation treatment to kill remaining cancer cells
  4. maintenance chemotherapy given in lower doses in order to prolong remission(2,4)
  5. palliative chemotherapy to address particular cancer symptoms to improve the patient’s quality of life, without expecting to reduce the cancer(5).

Chemotherapy Candidacy

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.

Targeted and Hormonal Therapy

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.

Side Effects

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:

Side Effect

Alpecia (acute)

Typically associated with traditional systemic agents
Onset usually 7 to 10 days after chemotherapy (7)

Shave remaining hair from head
Reassurance as it will grow back

Nausea and vomiting

Typically associated with traditional systemic agents

  1. acute (within a few hours)
  2. delayed (> 24 hours)
  3. anticipatory (conditioned response)

Depends on the intrinsic emetogenic potential of the specific agent or regimen used

Nonpharmacologic options:

  1. Small light meals several times per day
  2. Try dry starchy foods like crackers
  3. Avoid vestibular stimulation by resting in bed or chair
  4. Behavioural therapy /desensitization for anticipatory emesis
  5. Sleep (11)

Pharmacologic options:

  1. 5-HT3 receptor antagonists (ie. Ondansetron)
  2. Neurokinin-1 receptor antagonists (ie. Aprepitant)
  3. Glucocorticoids (ie. Dexamethasone)
  4. Olanzapine


Typically associated with traditional systemic agents
Usually defined as an absolute neutrophil count < 1.5 or 1 × 109/L
Severe neutropenia <0.5 × 109/L
Fever defined as any single oral T ≥ 38.3 °C or ≥ 38 °C for 1 hour

Can consider g-CSF as primary or secondary prophylaxis to prevent neutropenia from chemo
If accompanied by fever it is an oncologic emergency and requires risk stratification and management with antibiotics +/- g-CSF (9)

Oral mucositis

Most traditional chemotherapeutic agents may cause or contribute to oral mucositis
Defined as acute inflammation or ulceration of the oral or oropharyngeal mucosal membranes which can interfere with eating, swallowing, or speech due to pain and discomfort (10)
Onset is shortly after chemotherapy and peaks at 7 days
Combined chemotherapy and radiotherapy to head and neck increases risk of severe oral mucositis
Can be worsened by drugs that lead to a dry mouth

Non pharmacological options:

  1. 8-12 cups of fluid intake unless contraindicated
  2. avoid spicy or acidic foods, alcohol, cigarette smoking
  3. complete all major dental work before starting chemotherapy
  4. maintain good oral hygiene (floss daily provided no pain, bleeding longer than 2 minutes, or low platelet count; brush with soft nylon brush)
  5. cryotherapy (ice chips, popsickles, cold water 5 minutes before, during, and 30 minutes after) for patients receiving bolus 5-flurouracil

Pharmacologic options:

  • mouth rinses:
    • normal saline
    • "magic mouthwash” (although limited evidence over bland rinses)
    • topical lidocaine mouthwash
    • avoid alcohol containing mouthwashes (10)

Weight loss

Nausea, anorexia, changes in taste may contribute to poor nutrition
Cachexia which is characterized by a hypercatabolic state leading to weight loss despite nutritional supplementation may occur in 80% of patients with advanced cancer (7)

Smaller more frequent meals and nutrient dense liquid supplements
Dietician assessment and plan

Peripheral neuropathy

More common with traditional systemic chemotherapies (platinum agents, microtubule inhibitors)
The incidence depends on the drug, and cumulative dose
Symmetric distal “stocking and glove” distribution affecting sensory in vast majority of cases

Consider dose adjustment or less neurotoxic alternative
No established drugs for prophylaxis
Possible pharmacologic options include gabapentin or duloxetine(12)

Secondary cancer

Some chemotherapy (alkylating agents, platinum agents, topoisomerase inhibitors, anthracyclines) have been associated with second cancers
Highest risk for leukemia is 5-10 years after treatment then declines
Myelodysplastic syndromes and acute myelogenous leukemia are the most common second cancers from chemotherapy
Some solid tumors have been linked to chemo (particularly for testicular cancer)
Targeted therapies used for melanoma targeting the BRAF protein may increase risk of squamous cell carcinomas of skin(13)

Follow up care ongoing surveillance as appropriate
Some cancer centers offer survivorship programs
Maintain good health by achieving a healthy weight, be physically active, healthy diet, limit alcohol, avoid tobacco (13)


  • Chemotherapy is systemic drug therapy used to kill cancer cells and typically works by interfering with DNA, interfering with cell division, or interfering with metabolism required for cell replication.

  • Targeted biologic and small molecule agents are more specific for cancer cells. Immunotherapies help use the patient’s own immune systems ability to recognize and eradicate cancer.

  • Hormonal agents are often useful for treating breast and prostate cancers as their growth is often driven by estrogen and androgens respectively.

  • Some common toxicities of chemotherapy include alopecia, nausea, vomiting, neutropenia, and secondary cancers.

Virtual Patient Case

Use your mouse to click through the slides and answer each question in the text box provided.
Note: This case can be completed on an iPad. To do this download the (free) Articulate Mobile Player for the iPad by clicking here.


  1. Systemic Therapy (Chemotherapy) [Internet]. [cited 2019 Jan 21]. Available from: http://www.bccancer.bc.ca/our-services/treatments/systemic-therapy-(chemotherapy)
  2. PhD RAH, PhD MAC, PharmD RF, BCPP JARP, BCPS KWP. Pharmacology. Fifth, North American edition. Baltimore, MD: LWW; 2011. 608
  3. Wellstein A, Giaccone G, Atkins MB, Sausville EA. Pathway-Targeted Therapies: Monoclonal Antibodies, Protein Kinase Inhibitors, and Various Small Molecules. In: Brunton LL, Hilal-Dandan R, Knollmann BC, editors. Goodman & Gilman’s: The Pharmacological Basis of Therapeutics [Internet]. 13th ed. New York, NY: McGraw-Hill Education; 2017 [cited 2019 Feb 4]. Available from: accessmedicine.mhmedical.com/content.aspx?aid=1154989738
  4. Chu E. Cancer Chemotherapy. In: Katzung BG, editor. Basic & Clinical Pharmacology [Internet]. 14th ed. New York, NY: McGraw-Hill Education; 2017 [cited 2019 Jan 21]. Available from: accessmedicine.mhmedical.com/content.aspx?aid=1148441711
  5. CME final.pdf [Internet]. [cited 2019 Jan 21]. Available from: http://cphm.ca/uploaded/38/web/CME%20final.pdf
  6. Chemotherapy and other drug therapies - Canadian Cancer Society [Internet]. www.cancer.ca. [cited 2019 Apr 24]. Available from: https://www.cancer.ca:443/en/cancer-information/diagnosis-and-treatment/chemotherapy-and-other-drug-therapies/?region=on
  7. Smith GF, Toonen T. Primary Care of the Patient with Cancer. Am Fam Physician. 2007 Apr 15;75(8):1207.
  8. Prevention and treatment of chemotherapy-induced nausea and vomiting in adults - UpToDate [Internet]. [cited 2019 Apr 29]. Available from: https://www.uptodate.com/contents/prevention-and-treatment-of-chemotherapy-induced-nausea-and-vomiting-in-adults?search=nausea%20cancer&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2
  9. Risk assessment of adults with chemotherapy-induced neutropenia - UpToDate [Internet]. [cited 2019 May 1]. Available from: https://www.uptodate.com/contents/risk-assessment-of-adults-with-chemotherapy-induced-neutropenia?search=neutropenia%20chemotherapy&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1
  10. Oral Mucositis.pdf [Internet]. [cited 2019 May 1]. Available from: http://www.bccancer.bc.ca/nursing-site/Documents/12.%20Oral%20Mucositis.pdf
  11. RxTx [Internet]. [cited 2019 Apr 29]. Available from: https://www-myrxtx-ca.ezproxy.library.ubc.ca/search
  12. Prevention and treatment of chemotherapy-induced peripheral neuropathy - UpToDate [Internet]. [cited 2019 Apr 30]. Available from: https://www.uptodate.com/contents/prevention-and-treatment-of-chemotherapy-induced-peripheral-neuropathy?search=neuropathy%20chemotherapy&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#H523404555
  13. How does chemotherapy affect the risk of second cancers? | American Cancer Society [Internet]. [cited 2019 Apr 30]. Available from: https://www.cancer.org/treatment/treatments-and-side-effects/physical-side-effects/second-cancers-in-adults/chemotherapy.html

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