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After completing this module, students should be able to:
1. Understand the specific classes of traditional systemic chemotherapy used in the treatment of cancer.

2. Understand the principles of targeted therapies including hormonal treatments, monoclonal antibodies and small molecule agents.

This module is an introduction to chemotherapies. It will discuss the broad classes of chemotherapies and will provide some examples for common indications (where applicable) as well. The broad classes of chemotherapies in this module include antimetabolites, antitumor antibiotics, alkylating agents, microtubule inhibitors, platinum agents, and the topoisomerase inhibitors. Furthermore, it will discuss hormonal agents, as well as introduce targeted therapies like monoclonal antibodies and tyrosine kinase inhibitors.

Cell Physiology

Review of the cell cycle:
The cell cycle is the process of events that a cell goes through in order to divide. An understanding of the cell cycle is helpful to understand chemotherapies. Many agents work by damaging DNA which makes them most effective on the S phase of rapidly dividing cells. Other agents target cell division by working at the M phase. Although this is beneficial for killing rapidly growing cancer cells, it also confers toxicity on rapidly proliferating normal cells like in the bone marrow, hair follicles, and intestinal epithelium (1).

G0 Resting Phase   
Cells that are not actively cycling are in the resting or quiescent state. Some cells can remain permanently in G0 and never undergo division and other cells can go in and out of G0. Furthermore, some rapidly dividing cells may go directly from mitosis into G1 and not enter G0. Most cells are in the G0 state.

G1 First Growth Phase
In G1 the cell is preparing for cell division by upregulating synthesis of proteins, enzymes, macromolecules and organelles. Growth is dependent on mitogens which function via cyclin dependent kinases in order to promote new cell development. As the cell completes G1 it passes through the G1-S checkpoint. This checkpoint may arrest cell cycle progression if DNA damage has occurred. This allows for DNA repair to occur before proceeding. Once past this check point, the cell becomes committed to cell division.

S Synthesis Phase
In this phase the cell replicates each chromosome. Within S phase there is another checkpoint for DNA damage repair. Chemotherapeutics that interfere with DNA synthesis work in S phase.

G2 Second Growth Phase
G2 involves growth prior to mitosis. DNA damage or unreplicated DNA can lead to a signal which arrests the cell cycle at the G2-M checkpoint(2).

M Mitosis Phase
Finally, M phase is where the cell divides through the process of mitosis. Vinca alkaloids and taxanes are chemotherapeutic classes that work in M phase by disrupting the formation of the mitotic spindle. There is also another checkpoint which attempts to ensure each daughter cell receives an equal set of chromosomes.

Cell cycle regulation:
Cell cycle division is regulated through several cell cycle checkpoints: G1-S, S, G2-M, and M phase checkpoints. These transitions are largely mediated by cyclin dependent kinases (CDK’s) which bind with specific cyclin proteins. Cyclin binding stimulates the enzymatic activity and substrate selection of the CDK. Thus, cyclin-CDK complexes allow the cell to move forward throughout the cell cycle(3).

Drug Classes

Antimetabolites (S Phase):

Antimetabolite drugs interfere with synthesis of DNA required for replicating cells. They do this by acting as antagonists of folic acid (ie. methotrexate), purines (mercaptopurine, thioguanine), or pyrimidines (fluorouracil, cytarabine, gemcitabine)(4). As a result, these agents are usually cell-cycle specific for S-phase and their toxicity tends to affect other rapidly proliferating cells like in the gastrointestinal tract and bone marrow. Antifolate agents inhibit the de novo synthesis of nucleotides like thymidine which are required to produce DNA strands. Other antimetabolites are purine or pyrimidine analogues which can inhibit formation of normal nucleotides, or arrest DNA synthesis by the incorporation of an abnormal nucleotide into a replicating DNA strand (3). Some important antimetabolites are described below:


Indications: Wide spectrum of malignant and non-malignant diseases. Most often for acute leukemia, lymphoma, breast cancer, bladder cancer, squamous cell cancers, and sarcomas(5).
MOA: Folate analogue which inhibits dihydrofolate reductase (DHFR). Folic acid is normally reduced to tetrahydrofolate (THF) by DHFR which an important donor of carbon in purine and thymidine synthesis. 
SE: Nausea, vomiting, diarrhea, stomatitis, myelosuppression, erythema, rash, urticaria, and alopecia. Methotrexate’s 7-OH metabolite may precipitate in renal tubules and can cause renal damage. Can also cause pulmonary toxicity, hepatotoxicity and cirrhosis. Leucovorin can reduce side effects as it is taken up more by normal cells than tumor cells and bypasses DHFR (6).

Leucovorin (folinic acid)

MOA: Acts as a rescue from methotrexate as it does not require dihydrofolate reductase to produce tetrahydrofolate (THF). In contrast to methotrexate, leucovorin enhances effects of    5-Fluorouracil as leucovorin produces more reduced folate which acts as a coenzyme needed for thymidylate synthase inhibition.

6-mercaptopurine (6-MP) and Azathioprine

Indications: Acute lymphocytic and myelogenous leukemia. Small cell non Hodgkin lymphomas(7).
MOA: 6-MP is an analogue of hypoxanthine/guanine and is converted to 6-MP-ribose phosphate (also known as 6-thioinosinic acid (TIMP)) by hypoxanthine-guanine phosphoribosyl transferase (HGPRT). TIMP inhibits purine synthesis and reduces levels of IMP, AMP, GMP. TIMP also converts to thioguanine monophosphate (TGMP) which will incorporate into DNA and RNA and cause cell cycle arrest. Azathioprine is an oral pro drug of 6-MP(6).
SE: Myelosuppression. Anorexia, nausea, vomiting, diarrhea and hepatotoxicity. Azathioprine and 6-MP are metabolized by xanthine oxidase, and thus allopurinol and febuxostat (xanthine oxidase inhibitors) can increase levels of 6-MP and cause myelosuppression.


Indications: Acute lymphocytic and myelogenous leukemia.
MOA: Works very similarly to 6-MP. Analogue of hypoxanthine/guanine and is converted to 6-thioguanylic acid (TGMP) by HGPRT. This leads to reduced synthesis of purines and cell cycle arrest when incorporated into DNA(6).
SE: Bone marrow suppression, Long term liver toxicity.


Indications:Hairy cell leukemia
MOA: An analogue of adenosine which terminates DNA replication and also causes DNA strand breaks leading to apoptosis.
SE: Myelosuppression, fever, peripheral neuropathy(7)


Indications: Chronic lymphocytic leukemia, low grade lymphomas, and acute myeloid leukemia (5). MOA: Is an analogue of adenosine. It inhibits DNA polymerase and terminates DNA and RNA replication(3). SE: Myelosuppression, Neurotoxicity (dose-dependent)(5).

5-Fluorouracil (IV or topical) or Capecitabine (PO)

Indications: Colon, rectum, gastric, pancreas, breast carcinomas and a wide range of other neoplasms in combination with other regimens. Also comes in a topical form for cutaneous neoplasms and disorders(5).
MOA: Fluorinated uracil molecule which forms 5-flurodeoxyuridinemonophosphate (5-FdUMP) which blocks thymidylate synthase which starves cell of thymidine(6). 5-FdUMP acts as a pseudosubstrate and becomes trapped with thymidylate synthase, and the coenzyme n5-n10-methylene tetrahydrofolic acid. Leucovorin drives process further by producing more coenzyme thus further inhibiting thymidylate synthase enzymes. Capecitabine is an oral formulation of 5-FU which is enzymatically converted to 5-FU requiring thymidine phosphorylase. Thymidine phosphorylase activity is concentrated primarily in tumor cells, and thus capecitabine is somewhat tumor specific.
SE: Nausea, vomiting, diarrhea, alopecia, severe ulceration of oral and GI mucosa, bone marrow suppression. Hand foot syndrome or erythematous desquamation is another side effect(6).

Floxuridine (2-deoxy-5-FU)

Indications: Used in palliative treatment of liver metastases of GI adenocarcinoma in liver.
MOA: Analog of 5-FU which is readily turned into 5-FU in the liver.
SE: Nausea, vomiting, diarrhea, stomatitis(6)


Indications: Acute myelogenous leukemia, acute lymphoblastic lymphoma, and non-Hodgkin lymphoma(7)
MOA: Is a pyrimidine (cytidine) analogue which when incorporated into DNA during replication causes chain termination and inhibits DNA polymerase.
SE: Myelosuppression, neurologic toxicity(5)


Indications Pancreatic, ovarian, lung, bladder cancers(7)
MOA: Analogue of nucleoside deoxycytidine which replaces cytosine in DNA synthesis. This leads to inhibited DNA synthesis.
SE: Myelosuppression, nausea, vomiting, alopecia, flu like symptoms, elevated transaminases, proteinuria, hematuria(6).


Indications: Chronic myelogenous leukemia and other myeloproliferative disorders (polycythemia vera, essential thrombocytosis) (5). 
MOA: Blocks DNA synthesis with little effect on RNA synthesis. Inhibits conversion of ribonucleotides to deoxyribonucleotides by blocking ribonucleotide reductase. Specific to S-phase of the cell cycle (7).
SE: Myelosuppression

Antitumor Antibiotics (CCNS):
Antitumor antibiotics include dactinomycin, anthracyclines, bleomycin and mitomycin(4). The anti tumour antibiotics are derived from streptomyces bacteria(8). Some examples are described below:

Dactinomycin (Actinomycin D)

Indications: Wilms tumor, rhabdomyosarcoma, Ewing, Kaposi and other sarcomas(5)
MOA: Intercalates and forms a dactinomycin-DNA complex between guanine and cytosine in DNA. This interferes with DNA dependent RNA polymerase and to a lesser degree DNA synthesis. It also causes single strand DNA breaks.
SE: Bone marrow suppression, nausea, vomiting, diarrhea, stomatitis, alopecia.

Doxorubicin and daunorubicin (CCNS)

Indications: Wide spectrum of cancers most commonly breast, adult sarcomas, pediatric solid tumours, Hodgkin and non-Hodgkin lymphomas and ovarian cancer(5).
MOA: Anthracycline class of chemotherapeutics work in multiple ways including inhibiting topoisomerase II, intercalating DNA and preventing transcription/replication, and generating free radicals which causes oxidative stress. 
SE: Permanent cardiotoxicity and congestive heart failure as a result of free radical formation. Myelosuppression, stomatitis, nausea, vomiting, diarrhea.Note: Dexrazoxane is an inhibitor of iron mediated free radical formation which may protect against anthracycline mediated cardiotoxicity(4).
Note: Dexrazoxane is an inhibitor of iron mediated free radical formation which may protect against anthracycline mediated cardiotoxicity(4).

Bleomycin (G2-M Phase)

Indications: Testicular cancer, lymphomas, local bladder cancer treatment.
MOA: Bleomycin is a combination of copper chelating glycopeptides which cause oxidative damage to DNA which leads to single strand and double strand DNA breaks. It causes cells to arrest in G2 phase and is cell cycle specific.(6)
SE: Pulmonary toxicity (pneumonitis and fibrosis), mucocutaneous reactions like hyperkeratosis, alopecia and blisters may form(4)

Mitomycin C (CCNS)

Indications: Bladder cancer (intravesicle)(7), stomach, pancreas adenocarcinomas, breast and lung cancers(5).
MOA: Is also derived from streptomyces bacteria and has a mechanism similar to the alkylating agents by cross linking DNA.
SE: Myelosuppression, heart, liver, lung, kidney toxicity(4).

Alkylating Agents (CCNS):

Alkylating agents are cell cycle non specific drugs which contain alkyl groups that form reactive molecular species that interact with and cross link DNA. This effectively halts DNA replication. Alkylating agents can have 1 (monofunctional) or 2 (bifunctional) reactive alkylating groups. Of these, the bifunctional alkylating agents are able to cross link between strands of DNA and are most effective(3). 


Indications: Hodgkins lymphoma, cutaneous T-cell lymphoma(5)
MOA: Alkylates the N7 nitrogen of a guanine in DNA which leads to cross-links between guanines. Halts DNA replication and cause DNA damage.
SE: Myelosuppression, immunosuppression, reactivation of viral infections, CNS related nausea/vomiting (can pre-treat with Ondansetron)(6).


Indications: Wide variety of cancers. ALL, CLL, Hodgkin and non-Hodgkin lymphoma, multiple myeloma, neuroblastoma, breast, ovary, Wilms tumor, sarcomas (7)
MOA: Prodrug converted to acrolein and phosphoramide mustard which is the active alkylating agent.
SE: Alopecia, nausea, vomiting, diarrhea, myelosuppression, hemorrhagic cystitis/bladder fibrosis as a result of acrolein metabolite. MESNA (sodium 2-mercaptoethane sulfonate) inactivates acrolein reducing this side effect. Also affect germ cells causing testicular atrophy, sterility, amenorrhea. 

Nitrosoureas: Carmustine and Lomustine

Indications: Malignant gliomas, Hodgkin and non-Hodgkin lymphomas(7)
MOA: Major action is its alkylation of DNA at the O6-guanine position. Good penetration of CNS.
SE: Myelosuppression, pulmonary fibrosis, interstitial nephritis(5). 


Indications: High dose prior to bone marrow transplant, Normal doses for CML (5)
MOA: Alkylating agent forming carbonium ions which cause myeloablation 
SE: Myelosuppression, skin changes, pulmonary toxicity and fibrosis

Microtubule Inhibitors (M Phase):
Microtubules are made up of polymers of tubulin protein and are responsible for formation of the mitotic spindle during cell division, as well as structural and transport roles in nerve cell axons. Microtubules can be assembled and disassembled and are dynamic structures within cells. The chemotherapeutic agents in this class are thought to target this dynamic effect. Vinca alkaloids inhibit the polymerization of tubulin monomers into microtubules. In contrast, taxane drugs promote microtubule stability, and thus impair breakdown required for cell division (3).

Vincristine (derived from periwinkle – Vinca Alkaloid)

Indications: Indications: Wide spectrum of cancers including Hodgkin and other lymphomas, rhabdomyosarcoma, neuroblastoma, Wilms tumor
MOA: Binds beta-tubulin and block polymerization of microtubules. This stops the cell in metaphase of mitosis.
SE: Neurotoxicity, peripheral neuropathy, myelosuppression(5)


Indications: Hodgkin and non-Hodgkin lymphoma, breast, bladder, lung, testicular cancer, Kaposi sarcoma, neuroblastoma (7)
MOA: Binds beta-tubulin and block polymerization of microtubules. This stops the cell in metaphase of mitosis.
SE: More myelosuppression than vincristine but lesser level of neurotoxicity.

Paclitaxel and docetaxel

Indications: breast, non small cell lung cancers, ovarian cancers, bladder, head and neck cancer (5)
MOA: Active in G2/M phase. Bind to beta-tubulin and instead of blocking polymerization like vinca alkaloids, taxanes promote and stabilize microtubules which then become non functional.
SE: Hypersensitivity, Neutropenia, peripheral neuropathy

Platinum Agents (CCNS):
Platinum agents work in a similar way as alkylating agents in that they form inter and intrastrand DNA cross links at the N7 of guanine residues (3). 

Cisplatin, Carboplatin, Oxaliplatin

Indications: Wide spectrum of cancers including testicular, ovarian, and bladder cancers (5)
MOA: Similar to alkylating agents in that they bind n7-guanine residues causing cross-links which inhibits DNA replication and RNA synthesis. 
SE: Peripheral neuropathy, ototoxicity, nephrotoxicity , nausea, vomiting, myelosuppression. Cisplatin generally causes more nausea, vomiting, and nephrotoxicity than carboplatin; carboplatin associated more often with severe thrombocytopenia than cisplatin.

Topoisomerase Inhibitors (S Phase)
Topoisomerases are nuclear enzymes which function to relieve supercoils in DNA by cleaving then resealing DNA to allow for DNA replication and RNA transcription. Topoisomerase I cleaves one strand of DNA to relieve torsional strain and Topoisomerase II cleaves both DNA strands before resealing the DNA. Topoisomerase inhibitors prevent the resealing of the DNA which leads to inhibition of DNA synthesis and cell death. As a result topoisomerase inhibitors are cell-cycle specific for S-phase(3).


Indications: metastatic colon cancer, lung, ovarian, and lymphoma(5)
MOA: Blocks topoisomerase I
SE: Myelosuppression, nausea, vomiting, diarrhea

Etoposide (derived from podophyllum)

Indications: Lung cancers, lymphoma(5)
MOA: Blocks topoisomerase II
SE: Myelosuppression, alopecia, anaphylactic reactions

Hormonal therapies:
Certain cancers may be dependent on or regulated by sex hormones like estrogen and androgens. Most notably breast cancer and prostate cancer respectively can be responsive to hormonal deprivation or blocking treatment(9). Some examples of hormonal therapies are selective estrogen receptor modulators (SERMS), Aromatase inhibitors, GnRH agonists, GnRH antagonists, and anti-androgens. Glucocorticoids can also be used in combination for leukemias and lymphomas by reducing lymphoid mass and at high doses causing breakdown of lymphocytes(6).

Selective estrogen receptor modulators (SERMs) have different effects (agonism, partial agonism, antagonism) at estrogen receptors depending on which tissue that estrogen receptor is.


Indications: Estrogen responsive breast cancer. Palliative treatment of metastatic breast cancer and as adjuvant therapy after radiation or surgery.
MOA: Competes with estrogen for the hormone binding receptor which is found intracellularly. Produces a nuclear complex which decreases estrogen stimulated DNA synthesis. Acts as an antagonist in breast tissue. Acts as an agonist on estrogen receptors in bone and the endometrium.
SE: Hot flashes, vaginal bleeding, deep vein thrombosis, endometrial hyperplasia and malignancy (6).


Indications: Risk reduction of breast cancer in those at high risk(6)
MOA: Same mechanism as tamoxifen, except has different tissue effects. Antagonist at breast tissue, partial agonist at bone, and no effect on endometrial tissue.
SE: Hot flashes, deep vein thrombosis (10)

Post menopausal women produce the bulk of their estrogens from the actions of aromatase enzyme which is a target of treatment in estrogen responsive cancers.

Anastrozole, Letrozole

Indications: Estrogen responsive breast cancer in postmenopausal women.
MOA: Estrogen responsive breast cancer in postmenopausal women.
SE: Hot flashes, reduced bone mineral density, arthralgias (9), and dyslipidemia


Indications: Estrogen responsive breast cancer in postmenopausal women
MOA: Irreversible aromatase inhibitor.
SE: Hot flashes, reduced bone mineral density, arthralgias(9)

Leuprolide, Goserelin

Indications: Prostate cancer androgen deprivation therapy, combined therapy with AI in pre-menopausal women with advanced breast cancer
MOA: Analogues of GnRH which stimulate the anterior pituitary. Constant stimulation of the GnRH receptor leads to desensitization of the anterior pituitary.
SE: Initial flare of androgen which then goes down to castration levels. Paired with anti-androgens (ie.flutamide) in initial phase. Impotence, hot flashes, gynecomastia.(9)


Indications: Prostate cancer androgen deprivation therapy
MOA: Antagonist of GnRH receptor which prevents action of GnRH on anterior pituitary.
SE: No initial flare. Impotence, hot flashes, gynecomastia.(9)


Indications: Complete androgen blockade with GnRH agonist/antagonists, or combined with GnRH agonists to block actions of initial flare of testosterone before HPA is desensitized.
MOA: Block androgen receptor interaction with testosterone
SE: Gynecomastia, GI distress, hot flashes(9)

Targeted and Biological therapies:
Targeted therapies are newer anticancer agents which are more specific for molecular pathways involved in the cancer process. Examples of targets of these treatments include cellular kinases, cell surface proteins, aberrant angiogenesis, growth factors/receptors, and restoration of immune recognition of cancer cells(11).  Targeted agents can be monoclonal antibodies against cell surface or other antigens (ie. growth factors, receptor ligands) which are released from cancer cells as well as small molecule agents which enter cells and can target intracellular products (ie. kinases)(11). 

Monoclonal antibodies are derived from cell culture and are directed against a specific antigen. Because of this specificity they generally have less side effects. They can kill cancer cells by blocking cell surface receptors, receptor ligands, or inducing immune cells or activating complement against the antigen-antibody complex(11). Monoclonal antibodies can also be used to deliver chemotherapy, or radionuclides directly to cancer cells thereby preventing exposure of these agents to non cancer cells. They require parenteral administration, and all may have infusion reactions as side effects. Infusion reactions can include fever, chills, nausea, dyspnea, and rashes. Monoclonal antibodies are named with the suffix -mab (11).

Trastuzumab (Herceptin)

Indications: Estrogen responsive breast cancer in postmenopausal women.
MOA: HER-2 is a human epidermal growth factor receptor (a type of cell surface receptor) which activates downstream pathways involved in cancer growth. Trastuzumab is an IgG antibody which selectively blocks HER-2 on tumor cells which overexpress this receptor. This leads to reduced signal transduction as well as antibody-dependent cell mediated cytotoxicity (ADCC) (11).
SE: Cardiotoxicity, reduction in left ventricular ejection fraction, and less commonly heart failure symptoms. Is worsened by prior anthracycline exposure. Generally, trastuzumab cardiotoxicity is reversible on cessation of the drug(12).

Cetuximab (Erbitux)

Indications: Metastatic colorectal cancer, advanced non-small cell lung cancers, metastatic renal cell cancers(5).
MOA: IgG antibody that binds vascular endothelial growth factor (VEGF). This prevents VEGF interaction with receptors on endothelial cell surfaces and inhibits angiogenesis(11).
SE: Bleeding, hypertension, GI perforation(5).

These agents can enter cells and exert their action against intracellular targets of molecular pathways which are amplified in cancer cells. Many of these pathways are mediated by protein kinases. In contrast, traditional chemotherapies target DNA and are less specific for cancer cells. Small molecule targeted agents generally can be administered orally. Small molecule agents end in the suffix -nib. Tyrosine Kinase inhibitors are a prominent example. Other examples include cyclin-dependent kinase inhibitors, and proteasome inhibitors. There are many more small molecule targeted therapies that are beyond the scope of this module.

Imatinib (Gleevac)

Indications: Chronic Myeloid Leukemia, c-kit + GI stromal tumors(5)
MOA: Imatinib is a tyrosine kinase inhibitor active against the constitutively active BCR-ABL fusion protein which arises from the Philadelphia chromosome. The Philadelphia chromosome is involved in the cells of most patients with CML and is a result of the translocation of the long arms of chromosome 9 and 22. If not blocked, CML may progress. Imatinib binds the BCR-ABL protein and locks it into an inhibited state(3).  In addition Imatinib also binds other tyrosine kinases including platelet derived growth factor receptors and c-kit which is involved in GI stromal tumors when constitutively active(3).
SE: Myelosuppression, hepatotoxicity, fluid retention(5)

Gefitinib (Iressa)

Indications: Non small cell lung cancer
MOA: Targets the EGFR tyrosine kinase by competitively blocking ATP required for kinase activity
SE: Diarrhea, papulopustular skin reactions(11)

Systemic Therapy Drug Summary

Some uses
Mechanism of action
Unique side effects


Wide spectrum of cancers

Folate analogue and inhibits dihydrofolate reductase. Depletes purines and thymine nucleotides necessary for DNA synthesis.

Myelosuppression, hepatotoxicity, nephrotoxic, pulmonary toxicity
Leucovorin reduces effect.



Inhibits purine nucleotide synthesis

Myelosuppression, hepatotoxicity



Inhibits purine nucleotide synthesis

Myelosuppression, hepatotoxicity


Hairy Cell Leukemia

Adenosine analogue
Causes DNA breakage

Myelosuppression, hepatotoxicity, neuropathy



Adenosine analogue which inhibits DNA polymerase when incorporated into DNA

Myelosuppression, hepatotoxicity, neurotoxicity

Capecitabine/5-Fluorouracil (5-FU)

Capecitabine: Breast, Colorectal cancer
5-FU: Wide spectrum of cancers. Topical for skin cancers

Pyrimidine analogue. Inhibits thymidylate synthase which depletes thymidine needed for DNA/RNA synthesis
Capecitabine is an oral prodrug of 5-FU.

Oral mucositis, myelosuppression, Hand-Foot syndrome
Leucovorin enhances effect


Palliative treatment of liver metastases from GI adenocarcinoma

Analogue of 5-FU activated by live.

Mucositis, nausea, vomiting, diarrhea.


AML, ALL, CML, NHL, meningeal neoplasms

Pyrimidine analogue which inhibits DNA polymerase

Myelosuppression, neurologic toxicity.


Lung cancers, pancreatic, breast, ovarian cancers

Pyrimidine analogue which inhibits DNA polymerase and causes chain termination

Myelosuppression, hepatotoxicity, hematuria


Head and neck cancer, CML, melanoma, ovarian cancer, myeloproliferative disorders

Inhibits ribonucleotide reductase necessary for DNA synthesis


Antitumor antibiotics

Dactinomycin (Actinomycin D)

Gestational trophoblastic tumour, rhabdomyosarcoma, Wilms tumour, Ewing Sarcoma

Intercalates DNA between guanine-cyotosine pairs in DNA which inhibit RNA > DNA polymerases.

Myelosuppression, stomatitis

Anthracyclines (ie. Doxorubicin or daunorubicin)

Wide spectrum of cancers

Inhibit topoisomerase II, Intercalate DNA, Generate free radicals and oxidative stress

Cardiotoxicity (permanent), myelosuppression


Testicular cancer, lymphomas, wide spectrum of cancers.

Copper chelating glycopeptides that bind DNA and cause strand breaks

Pulmonary toxicity (pneumonitis and fibrosis)


Bladder (intravesicle), colon, gastric cancers

Causes cross links between DNA (similar to alkylating agents)

Myelosuppression, heart, liver, lung, kidney toxicity

Alkylating agents


Hodgkin lymphoma, cutaneous T-cell lymphoma

Covalently cross link DNA strands by alkylating N7 nitrogen of guanine

Myelosuppression, immunosuppression


Wide spectrum of cancers

Prodrug activated by liver into acrolein and phosphoramide which covalently cross links DNA strands

Acrolein can cause hemorrhagic cystitis/bladder fibrosis, infertility

Nitrosoureas (ie. Carmustine)

Brain tumours, glioma, lymphomas, multiple myeloma, melanoma, GI cancers

Alkylate DNA at O-6 guanine position

Myelosuppression, pulmonary fibrosis, interstitial nephritis


Conditioning prior to bone marrow transplant, CML

Covalently cross link DNA strands by alkylating N7 nitrogen of guanine

Myelosuppression, skin changes, pulmonary toxicity

Microtubule inhibitors


Wide spectrum of cancers including non-hodgkin lymphoma

Inhibit polymerization of microtubules stopping cells in mitosis

Neurotoxicity, peripheral neuropathy, myelosuppression


Kaposi sarcoma, lymphomas, mycosis fungoides, testicular cancer

Inhibit polymerization of microtubules stopping cells in mitosis

Myelosuppression, peripheral neuropathy

Taxanes (ie.Paclitaxel)

Breast, NSCLC, ovarian, kaposi sarcoma

Promote and stabilize polymerization of microtubules arresting cells in mitosis.

Myelosuppression, peripheral neuropathy

Topoisomerase inhibitors


Colorectal cancers

Inhibit religation of DNA by blocking topoisomerase I



SCLC,NSCLC, lymphomas

Inhibit religation of DNA by blocking topoisomerase II


Hormonal therapies


Estrogen responsive breast cancers

SERM. Antagonist on breast tissue. Agonist on bone and endometrial tissue.

Hot flashes, vaginal bleeding, deep vein thrombosis, endometrial hyperplasia or malignancy


Risk reduction of breast cancer in those at high risk

SERM. Antagonist at breast. Agonist at bone but no effects on endometrial tissue.

Hot flashes, deep vein thrombosis

Anastrozole and Letrozole

Estrogen responsive breast cancer in post -menopausal women

Nonsteroidal competitive aromatase inhibitor

Hot flashes, reduced bone mineral density, arthralgias


Estrogen responsive breast cancer in post -menopausal women

Steroidal irreversible aromatase inhibitor

Hot flashes, reduced bone mineral density, arthralgias

Leuprolide, Goserelin

Androgen deprivation therapy in advanced prostate cancers

GnRH (aka: LHRH) agonists

Initial increase in androgen (pair with anti-androgen). Impotence, hot flashes, gynecomastia


Androgen deprivation therapy in advanced prostate cancers

GnRH (aka: LHRH) agonists

Impotence, hot flashes, gynecomastia


Use in combination initially to prevent effects of initial androgen flare from LHRH agonists

Antiandrogen which blocks androgen interaction with receptor

Impotence, hot flashes, gynecomastia

Targeted biological therapies


HER-2 + breast and gastric cancers

Antibody against HER-2 growth factor

Generally reversible cardiotoxicity


Metastatic colorectal cancer, advanced non-small cell lung cancers, metastatic renal cell cancers, metastatic ovarian cancers

Antibody against vascular endothelial growth factor (VEGF)

Bleeding, hypertension, GI perforation


Non-Hodgkin lymphoma, B-Cell lymphomas

Antibody against CD20 B cell surface antigen

Infusion reactions, reactivation of hep B, JC virus and progressive leukoencephalopathy


Metastatic colon cancers, head and neck squamous cell carcinomas

Antibody against epidermal growth factor receptor (EGFR)


Targeted biological therapies


CML, c-kit + GI stromal tumors

Tyrosine kinase inhibitor against the the constitutively active BCR-ABL protein kinase of the Philadelphia chromosome.

Myelosuppression, hepatotoxicity, fluid retention



Tyrosine kinase inhibitor against epidermal growth factor receptor


Virtual Patient Case

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