34 Anticancer drugs Flashcards
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
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
34.01 ALKYLATING AGENTS AND SIMILAR DRUGS (cancer agents that form covalent bonds with DNA and impede replication)
Nitrosoureas, e.g. carmustine, lomustine
cross the blood-brain barrier and used for tumours of brain and meninges
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
platinum agents are used in a wide range of cancers
however, they cause severe nausea/vomiting, nephrotoxicity and neuropathy
34.01 ALKYLATING AGENTS AND SIMILAR DRUGS (cancer agents that form covalent bonds with DNA and impede replication)
Others, e.g. busulfan, dacarbazine, hydroxycarbamide
commonly used in haematological malignancies, but also in soft tissue and skin tumours (dacarbazine) and in cervical cancer (hydroxycarbamide)
34.02 ANTIMETABOLITES (cancer agents that block synthesis of DNA/RNA via folate, pyrimidine or purine pathways)
Folate antagonists, e.g. methotrexate, pemetrexed
interfere with thymidylate synthesis
methotrexate very widely used in cancer and autoimmune disease
major toxicities are to the marrow, GIT, liver and lungs
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
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
34.02 ANTIMETABOLITES (cancer agents that block synthesis of DNA/RNA via folate, pyrimidine or purine pathways)
Purine analogues, e.g. cladribine, fludarabine, mercaptopurine
inhibit DNA synthesis
mainly used in treatment of leukaemia
34.03 CYTOTOXIC ANTIBIOTICS (cancer agents that interfere with DNA/RNA synthesis or topoisomerase action)
Anthracyclines, e.g. doxorubicin, daunorubicin, mitoxantrone
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
34.03 CYTOTOXIC ANTIBIOTICS (cancer agents that interfere with DNA/RNA synthesis or topoisomerase action)
Others, e.g. bleomycin, dactinomycin
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
34.04 PLANT DERIVATIVES (microtubule or topoisomerase inhibitors for cancer treatment)
Taxanes, e.g. paclitaxel, docetaxel
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
34.04 PLANT DERIVATIVES (microtubule or topoisomerase inhibitors for cancer treatment)
Vinca alkaloids, e.g. vincristine, vinblastine
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
34.04 PLANT DERIVATIVES (microtubule or topoisomerase inhibitors for cancer treatment)
Camptothecins, e.g. irinotecan, topotecan
obtained from stem of Camptotheca tree
inhibits topoisomerase I
main uses are for colorectal and lung cancer
34.04 PLANT DERIVATIVES (microtubule or topoisomerase inhibitors for cancer treatment)
Others, e.g. etoposide
derived from mandrake root
acts on DNA synthesis by inhibiting topoisomerase II and mitochondrial function
used in lung and testicular cancer, and leukaemia
34.05 HORMONES (hormone agonists, antagonists or synthesis modulators for cancer treatment)
Progesterones
used in endometrial cancer
34.05 HORMONES (hormone agonists, antagonists or synthesis modulators for cancer treatment)
GnRH analogues, e.g. leuprorelin, goserelin
typically used in prostate cancer, but also prescribed for ovarian suppression in premenopausal women who have hormone receptor-positive breast cancer
34.05 HORMONES (hormone agonists, antagonists or synthesis modulators for cancer treatment)
Somatostatin analogues, e.g. octreotide, lanreotide
used in treatment of tumours where cell proliferation is activated through somatostatin receptors
these are typically neuroendocrine tumours such as carcinoid, gastrinoma and glucagonomas
34.05 HORMONES (hormone agonists, antagonists or synthesis modulators for cancer treatment)
Anti-oestrogens, e.g. tamoxifen, fulvestrant
used in breast cancer
34.05 HORMONES (hormone agonists, antagonists or synthesis modulators for cancer treatment)
Aromatase inhibitors, e.g. anastrozole, letrozole, exemestane
used for breast cancer in postmenopausal women
aromatase is the enzyme responsible for synthesising oestrogen from androgens in the adrenal cortex
34.05 HORMONES (hormone agonists, antagonists or synthesis modulators for cancer treatment)
Anti-androgens, e.g. flutamide, bicalutamide
used in prostate cancer
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
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
34.06 PROTEIN KINASE INHIBITORS (cancer treatment with inhibitors of kinases involved in growth factor receptor transduction)
Pan-kinase inhibitors, e.g. sorafenib
inhibits multiple kinases
reduces tumour cell proliferation and new vessel formation
used in liver, kidney and thyroid cancers
34.07 MONOCLONAL ANTIBODIES (monoclonal antibodies targeted at cancer growth)
Epidermal growth factor inhibitors, e.g. trastuzumab, panitumumab
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
34.07 MONOCLONAL ANTIBODIES (monoclonal antibodies targeted at cancer growth)
Immune checkpoint inhibitors, e.g. ipilimumab, nivolumab
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
34.07 MONOCLONAL ANTIBODIES (monoclonal antibodies targeted at cancer growth)
Vascular endothelial growth factor inhibitors, e.g. bevacizumab, aflibercept
reduce vascular proliferation and new vessel formation
used in breast and colorectal cancer
34.08 ANTICANCER DRUGS
The main adverse effects of most cancer drugs (examples are the drugs that affect DNA and RNA synthesis and actions)
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
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)
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
