34 Anticancer drugs

Question 1

34.01 ALKYLATING AGENTS AND SIMILAR DRUGS (cancer agents that form covalent bonds with DNA and impede replication)

Nitrogen mustards, e.g. bendamustine, chlorambucil, cyclophosphamide

Answer 1

cyclophosphamide is very widely used, for a range of tumours and autoimmune disease because of its profound effect on lymphocytes
bendamustine and chlorambucil are often used for haematological malignancies

Question 2

34.01 ALKYLATING AGENTS AND SIMILAR DRUGS (cancer agents that form covalent bonds with DNA and impede replication)

Nitrosoureas, e.g. carmustine, lomustine

Answer 2

cross the blood-brain barrier and used for tumours of brain and meninges

Question 3

34.01 ALKYLATING AGENTS AND SIMILAR DRUGS (cancer agents that form covalent bonds with DNA and impede replication)

Platinum compounds, e.g. cisplatin, carboplatin, oxaliplatin

Answer 3

platinum agents are used in a wide range of cancers
however, they cause severe nausea/vomiting, nephrotoxicity and neuropathy

Question 4

34.01 ALKYLATING AGENTS AND SIMILAR DRUGS (cancer agents that form covalent bonds with DNA and impede replication)

Others, e.g. busulfan, dacarbazine, hydroxycarbamide

Answer 4

commonly used in haematological malignancies, but also in soft tissue and skin tumours (dacarbazine) and in cervical cancer (hydroxycarbamide)

Question 5

34.02 ANTIMETABOLITES (cancer agents that block synthesis of DNA/RNA via folate, pyrimidine or purine pathways)

Folate antagonists, e.g. methotrexate, pemetrexed

Answer 5

interfere with thymidylate synthesis
methotrexate very widely used in cancer and autoimmune disease
major toxicities are to the marrow, GIT, liver and lungs

Question 6

34.02 ANTIMETABOLITES (cancer agents that block synthesis of DNA/RNA via folate, pyrimidine or purine pathways)

Pyrimidine analogues, e.g. fluorouracil, capecitabine, gemcitabine, cytarabine

Answer 6

fluorouracil (and its prodrugs capecitabine and tegafur) interfere with thymidylate synthetase
widely used in GI and breast cancers
gemcitabine is converted to an analogue that inhibits DNA synthesis, and is widely used for a diverse range of cancers

Question 7

34.02 ANTIMETABOLITES (cancer agents that block synthesis of DNA/RNA via folate, pyrimidine or purine pathways)

Purine analogues, e.g. cladribine, fludarabine, mercaptopurine

Answer 7

inhibit DNA synthesis
mainly used in treatment of leukaemia

Question 8

34.03 CYTOTOXIC ANTIBIOTICS (cancer agents that interfere with DNA/RNA synthesis or topoisomerase action)

Anthracyclines, e.g. doxorubicin, daunorubicin, mitoxantrone

Answer 8

inhibit RNA and DNA synthesis (mainly acting on topoisomerase II)
used in a wide range of cancers such as breast and ovary
major toxicities are cardiac and myelosuppression

Question 9

34.03 CYTOTOXIC ANTIBIOTICS (cancer agents that interfere with DNA/RNA synthesis or topoisomerase action)

Others, e.g. bleomycin, dactinomycin

Answer 9

bleomycin is a mixture of glycopeptide antibiotics with cytotoxic properties, and is often used in germline cancers
major toxicity includes pulmonary fibrosis and mucocutaneous syndromes
dactinomycin has similar actions as anthracyclines without apparent cardiac toxicity

Question 10

34.04 PLANT DERIVATIVES (microtubule or topoisomerase inhibitors for cancer treatment)

Taxanes, e.g. paclitaxel, docetaxel

Answer 10

derived from bark of Pacific yew tree
act on microtubules to ‘freeze’ them in polymerised state
widely used, covering a broad range of tumours
neurotoxicity a major problem

Question 11

34.04 PLANT DERIVATIVES (microtubule or topoisomerase inhibitors for cancer treatment)

Vinca alkaloids, e.g. vincristine, vinblastine

Answer 11

derived from Madagascan periwinkle
bind to tubulin and inhibit the polymerisation and subsequent spindle formation, inhibits mitosis at metaphase
widely used, covering a broad range of tumours
neurotoxicity a major problem

Question 12

34.04 PLANT DERIVATIVES (microtubule or topoisomerase inhibitors for cancer treatment)

Camptothecins, e.g. irinotecan, topotecan

Answer 12

obtained from stem of Camptotheca tree
inhibits topoisomerase I
main uses are for colorectal and lung cancer

Question 13

34.04 PLANT DERIVATIVES (microtubule or topoisomerase inhibitors for cancer treatment)

Others, e.g. etoposide

Answer 13

derived from mandrake root
acts on DNA synthesis by inhibiting topoisomerase II and mitochondrial function
used in lung and testicular cancer, and leukaemia

Question 14

34.05 HORMONES (hormone agonists, antagonists or synthesis modulators for cancer treatment)

Progesterones

Answer 14

used in endometrial cancer

Question 15

34.05 HORMONES (hormone agonists, antagonists or synthesis modulators for cancer treatment)

GnRH analogues, e.g. leuprorelin, goserelin

Answer 15

typically used in prostate cancer, but also prescribed for ovarian suppression in premenopausal women who have hormone receptor-positive breast cancer

Question 16

34.05 HORMONES (hormone agonists, antagonists or synthesis modulators for cancer treatment)

Somatostatin analogues, e.g. octreotide, lanreotide

Answer 16

used in treatment of tumours where cell proliferation is activated through somatostatin receptors
these are typically neuroendocrine tumours such as carcinoid, gastrinoma and glucagonomas

Question 17

34.05 HORMONES (hormone agonists, antagonists or synthesis modulators for cancer treatment)

Anti-oestrogens, e.g. tamoxifen, fulvestrant

Answer 17

used in breast cancer

Question 18

34.05 HORMONES (hormone agonists, antagonists or synthesis modulators for cancer treatment)

Aromatase inhibitors, e.g. anastrozole, letrozole, exemestane

Answer 18

used for breast cancer in postmenopausal women
aromatase is the enzyme responsible for synthesising oestrogen from androgens in the adrenal cortex

Question 19

34.05 HORMONES (hormone agonists, antagonists or synthesis modulators for cancer treatment)

Anti-androgens, e.g. flutamide, bicalutamide

Answer 19

used in prostate cancer

Question 20

34.06 PROTEIN KINASE INHIBITORS (cancer treatment with inhibitors of kinases involved in growth factor receptor transduction)

Tyrosine kinase inhibitors, e.g. imatinib, vemurafenib, gefitinib, sunitinib

Answer 20

wide range of small molecules targeted at kinases involved in signalling pathways and cancer initiation and progression
often specific for tumours with identifiable genetic alteration, e.g. imatinib in chronic myeloid leukaemia, vemurafenib in melanoma, gefitinib in lung cancer

Question 21

34.06 PROTEIN KINASE INHIBITORS (cancer treatment with inhibitors of kinases involved in growth factor receptor transduction)

Pan-kinase inhibitors, e.g. sorafenib

Answer 21

inhibits multiple kinases
reduces tumour cell proliferation and new vessel formation
used in liver, kidney and thyroid cancers

Question 22

34.07 MONOCLONAL ANTIBODIES (monoclonal antibodies targeted at cancer growth)

Epidermal growth factor inhibitors, e.g. trastuzumab, panitumumab

Answer 22

bind to and inhibit the epidermal growth factor receptor (a tyrosine kinase receptor), to prevent activation, thus reducing cell proliferation
used in breast cancer (trastuzumab) and colorectal cancer (panitumumab)
cardiac toxicity with trastuzumab

Question 23

34.07 MONOCLONAL ANTIBODIES (monoclonal antibodies targeted at cancer growth)

Immune checkpoint inhibitors, e.g. ipilimumab, nivolumab

Answer 23

programmed cell death protein-1 and cytoxic T-lymphocyte associated protein-4 act to ‘stand down’ the immune system
inhibitors of these proteins can re-prime the immune system to recognise and destroy cancer cells in melanoma, lung, kidney, head and neck cancers

Question 24

34.07 MONOCLONAL ANTIBODIES (monoclonal antibodies targeted at cancer growth)

Vascular endothelial growth factor inhibitors, e.g. bevacizumab, aflibercept

Answer 24

reduce vascular proliferation and new vessel formation
used in breast and colorectal cancer

Question 25

34.08 ANTICANCER DRUGS

The main adverse effects of most cancer drugs (examples are the drugs that affect DNA and RNA synthesis and actions)

Answer 25

most anticancer drugs are cytotoxic (they damage or kill cells) and they are antiproliferative (they stop cells from dividing - both cancer cells and rapidly dividing normal cells)
thus they can: depress the bone marrow; impair healing; interfere with normal growth (in children); cause sterility; result in hair loss; be teratogenic
most also cause nausea and vomiting
different cytotoxic drugs manifest the above adverse effects to different degrees

Question 26

34.08 ANTICANCER DRUGS

The main adverse effects of newer, non-proliferative agents (examples are the drugs that do not affect DNA and RNA synthesis)

Answer 26

newer, non-proliferative agents target the underlying pathogenic mechanisms such as changes in: the relevant growth factors and/or their receptors; cell cycle control mechanisms; apoptotic pathways; telomerase expression; tumour-related angiogenesis
these agents are less likely to have cytotoxic actions but have their own adverse effects