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Antineoplastic agents
INN Reviews Chemical classification Preg. cat. Route[1] Mechanism of action[1][2][3][4] Indications[1][2][4] Major toxicities[1][2][4][5]
1. Cytotoxic antineoplastics
1.01 Nucleoside analogues
Azacitidine [6][7][8][9]
[10][11][12]
[13][14][15]		 Cytidine analogue X (Au) SC, IV DNA methyltransferase inhibitor and incorporates itself into RNA, hence inhibiting gene expression.[16] Myelodysplastic syndromes, acute myeloid leukaemiaand chronic myeloid leukaemia Myelosuppression, kidney failure (uncommon/rare), renal tubular acidosis andhypokalaemia.
Capecitabine [17][18][19]
[20][21][22]
[23][24][25]		 Uracil analogue D (Au) PO Fluorouracil prodrug Breast, colorectal, gastric and oesophageal cancer Myelosuppression, cardiotoxicity, hypertriglyceridaemia, GI haemorrhage (uncommon), cerebellar syndrome (uncommon), encephalopathy (uncommon) and diarrhoea.
Carmofur N/A Uracil analogue N/A PO Fluorouracil prodrug Colorectal, breast and ovarian cancer Myelosuppression, neurotoxicity and diarrhoea.
Cladribine MS:
[26][27][28]
[29][30][31]
[32][33][34]
[35]
Cancer:
[36][37][38]
[39]		 Adenosine analogue D (Au) PO, SC, IV DNA methyltransferaseinhibitor, metabolites incorporate themselves into DNA.[40] Hairy cell leukaemia, chronic lymphocytic leukaemia, Waldenstrom macroglobulinaemia and multiple sclerosis. Myelosuppression,haemolytic anaemia (uncommon), neurotoxicity (rare), renal impairment (rare), pulmonary interstitial infiltrates (rare), Stevens–Johnson syndrome (rare) and toxic epidermal necrolysis (rare).
Clofarabine [41][42][43]
[44][45][46]
[47][48][49]		 Deoxyadenosine analogue D (Au) IV Ribonucleotide reductase and DNA polymerase inhibitor.[50] Acute lymphoblastic leukaemia andacute myeloid leukaemia Myelosuppression, hypokalaemia, cytokine release syndrome, Stevens–Johnson syndrome(uncommon), toxic epidermal necrolysis (uncommon) and pancreatitis (uncommon)
Cytarabine [51][52][53] Cytidine analogue D (Au) SC, IM, IV, IT DNA polymerase inhibitor, S-phase specific. Incorporates its metabolites into DNA. Acute myeloid leukaemia, acute lymphoblastic leukaemia, chronic myeloid leukaemia, lymphomas,progressive multifocal leucoencephalopathy and meningeal leukaemia Myelosuppression, GI bleeds, pancreatitis (uncommon/rare),anaphylaxis (uncommon/rare), pericarditis (uncommon/rare) and conjunctivitis (uncommon/rare). High dose: cerebral and cerebellar dysfunction, ocular toxicity, pulmonary toxicity, severe GI ulceration and peripheral neuropathy (rare).
Decitabine [6][7][54]
[55][56][57]
[58][59][60]
[61][62]		 Cytidine analogue. D (US) IV DNA methyltransferase inhibitor. Myelodysplastic syndrome, sickle cell anaemia (orphan), acute myeloid leukaemia and chronic myeloid leukaemia. Myelosuppression, hyperglycaemia, hypoalbuminaemia, hypomagnesaemia, hypokalaemia, hyperkalaemia and thrombocythaemia.
Floxuridine [63] Uracil analogue D (US) IA Fluorouracil analogue. Metastatic GI adenocarcinoma and stomach cancer Myelosuppression.
Fludarabine [64][65][66]
[67][68][69]
[70]		 Adenosine analogue D (Au) PO, IV DNA polymerase and ribonucleotide reductase inhibitor. Acute myeloid leukaemia, chronic lymphocytic leukaemia, non-Hodgkin lymphoma and Waldenstrom macroglobulinaemia. Myelosuppression,hyperglycaemia, GI bleeds (uncommon), pneumonitis (uncommon), haemolytic anaemia (uncommon), severe neurotoxicity (rare),haemorrhagic cystitis (rare), Stevens–Johnson syndrome (rare) and toxic epidermal necrolysis (rare).
Fluorouracil [71][72][73] Uracil analogue D (Au) IV Thymidylate synthase inhibitor. Anal, breast, colorectal, gastric, head and neck, oesophageal and pancreatic cancer. Bowen's disease and actinic keratoses. Myelosuppression, diarrhoea, cardiotoxicity, GI ulceration and bleeding (uncommon), cerebellar syndrome (uncommon), encephalopathy (uncommon) and anaphylaxis (rare).
Gemcitabine [74][75][76]
[77][78][79]
[80]		 Deoxycytidine analogue D (Au) IV DNA synthesis inhibitor, induces apoptosis specifically in S-phase. Bladder, breast, nasopharyngeal,non-small cell lung, ovarian and pancreatic cancer, lymphomas andinflammatory bowel disease. Myelosuppression, pulmonary toxicity, kidney failure (rare), haemolytic uraemic syndrome(rare), thrombotic thrombocytopenic purpura (rare), anaphylactoid reaction (rare), reversible posterior leucoencephalopathy syndrome (rare), myocardial infarction (rare) and heart failure (rare).
Mercaptopurine [81][82] Hypoxanthine analogue D (Au) PO Purine synthesis inhibitor. Acute lymphoblastic leukaemia, acute promyelocytic leukaemia, lymphoblastic lymphoma and inflammatory bowel disease.[83] Myelosuppression, hepatotoxicity, GI ulceration (rare), pancreatitis (rare) and secondary leukaemia (rare) or myelodysplasia (rare).
Nelarabine[84] [85][86]
[87][88][89]
[90][91]		 Adenosine analogue D (US) IV Purine synthesis inhibitor. Acute lymphoblastic leukaemia and chronic lymphocytic leukaemia. Myelosuppression, pleural effusion, seizures, tumour lysis syndrome and a condition similar to Guillain-Barré syndrome.
Pentostatin [92][93][94]
[95][96][97]		 Adenosine analogue D (US) IV Adenosine deaminase inhibitor. Hairy cell leukaemia, peripheral T-cell lymphoma (orphan), cutaneous T cell lymphoma (orphan) and chronic lymphocytic leukaemia (orphan). Myelosuppression, neurotoxicity, immune hypersensitivity, hyponatraemia, thrombotic thrombocytopenic purpura and microangiopathic hemolytic anaemia.
Tegafur [98][99][100]
[101][102][103]
[104]		 Fluorouracilanalogue D (Au) PO Thymidylate synthase inhibitor. Breast, colorectal cancer, gallbladder, gastrointestinal tract, head and neck, liver and pancreas cancer. Myelosuppression, diarrhoea, neurotoxicity and hepatitis (rare).
Tioguanine [105][106][107]
[108][109]		 Guanine analogue. D (Au) PO Purine synthesis inhibitor. Acute lymphoblastic leukaemia and acute myeloid leukaemia Myelosuppression, hepatotoxicity, peripheral neuropathy (uncommon), intestinal necrosis (rare) and perforation (rare).
1.02 Antifolates
Methotrexate [110][111][112]
[113][114][115]		 Folate analogue D (Au) SC, IM, IV, IT, PO Dihydrofolate reductase inhibitor. Bladder and breast cancer. squamous cell carcinoma of head and neck, gestational trophoblastic disease, acute leukaemias, non-Hodgkin lymphoma, osteosarcoma, brain tumours, graft-versus-host disease and systemic sclerosis. Myelosuppression, pulmonary toxicity, hepatotoxicity, neurotoxicity (high dose or intrathecal administration), anaphylactic reactions (rare), Stevens–Johnson syndrome (rare), Toxic Epidermal Necrolysis (rare), kidney failure (rare), osteoporosis (rare), skin and bone necrosis (rare) and macrocytic anaemia (rare).
Pemetrexed [116][117][118]
[119][120][121]
[122][123]
[124][125][126]
[127][128][129]
[130][131][132]
[133][134][135]
[136][137][138]
[139][140][141]		 Folate analogue D (Au) IV Dihydrofolate reductase, thymidylate synthase and glycinamide ribonucleotide formyltransferase inhibitors. Malignant mesothelioma and non-squamous non-small cell lung cancer. Myelosuppression, renal impairment, peripheral neuropathy, Supraventricular tachycardia (uncommon), hepatitis (rare), colitis (rare), pneumonitis (rare), radiation recall (rare), Stevens–Johnson syndrome (rare) and toxic epidermal necrolysis (rare).
Raltitrexed [142][143][144]
[145][146][147]
[148][149]		 Quinazolinone D (Au) IV Dihydrofolate reductase and thymidylate synthase inhibitor. Colorectal cancer Myelosuppression
1.03 Other antimetabolites
Hydroxycarbamide [150][151][152]
[153][154][155]
[156][157][158]
[159]		 Urea analogue D (Au) PO Inhibits DNA synthesis by inhibiting the enzyme ribonucleotide reductase. Chronic myeloid leukaemia, essential thrombocytosis, polycythaemia vera, myelofibrosis, acute myeloid leukaemia and sickle cell anaemia Myelosuppression, skin cancer (rare), oedema (rare), hallucinations (rare), seizures (rare) and pulmonary toxicity (rare).
1.04 Topoisomerase I inhibitor
Irinotecan Camptothecin D (Au) IV Inhibits topoisomerase I. Colorectal cancer Diarrhoea, myelosuppression, pulmonary infiltrates (uncommon), bradycardia (uncommon), ileus (rare) and colitis (rare).
Topotecan Camptothecin D (Au) IV Inhibits topoisomerase I. Small cell lung cancer, ovarian cancer and cervical cancer Diarrhoea, myelosuppression, interstitial lung disease and allergy.
1.05 Anthracyclines
Daunorubicin Anthracycline D (Au) IV Inhibits DNA and RNA synthesis by intercalating DNA base pairs. Inhibits DNA repair by inhibiting topoisomerase II. Acute leukaemias Myelosuppression, cardiotoxicity, anaphylaxis (rare), secondary malignancies (particularly acute myeloid leukaemia and myelodysplastic syndrome) and radiation recall.
Doxorubicin Anthracycline D (Au) IV As above. Breast cancer, lymphomas, sarcomas, bladder cancer, acute lymphoblastic leukaemia, Wilms' tumour, AIDS-related Kaposi's sarcoma, neuroblastoma and multiple myeloma As above.
Epirubicin Anthracycline D (Au) IV As above. Breast cancer, gastric cancer and bladder cancer As above.
Idarubicin Anthracycline D (Au) IV, PO As above. Acute leukaemias. As above.
Mitoxantrone Anthracenedione D (Au) IV As above. Non-Hodgkin lymphoma, acute myeloid leukaemia,prostate cancer and multiple sclerosis As above.
Valrubicin Anthracycline C (US) IV As above. Bladder cancer. As above.
1.06 Podophyllotoxins
Etoposide Podophyllotoxin D (Au) IV, PO Topoisomerase II inhibitor. Testicular cancer, ovarian cancer, lung cancer, acute myeloid leukaemia, lymphomas and sarcomas Myelosuppression, hypersensitivity reactions, Stevens–Johnson syndrome (rare), peripheral neuropathy (uncommon) and secondary malignancies (especially acute myeloid leukaemia).
Teniposide Podophyllotoxin D (Au) IV Topoisomerase II inhibitor. Lymphomas, acute lymphoblastic leukaemia and neuroblastoma As above.
1.07 Taxanes
Cabazitaxel Taxane D (Au) IV Microtubule disassembly inhibitor. Arrests cells in late G2 phase and M phase. Prostate cancer Myelosuppression, diarrhoea, kidney failure, hypersensitivity, severe GI reactions (including perforation, ileus, colitis, etc.; all rare) and peripheral neuropathy
Docetaxel Taxane D (Au) IV As above. Breast cancer, non-small cell lung cancer, ovarian cancer, prostate cancer, squamous cell head and neck cancer and gastric cancer. Myelosuppression, peripheral neuropathy, hypersensitivity, fluid retention, heart failure (uncommon), pulmonary toxicity (rare), radiation recall (rare), scleroderma-like skin changes (rare), Stevens–Johnson syndrome (rare), toxic epidermal necrolysis (rare), seizures (rare) and encephalopathy (rare)
Paclitaxel Taxane D (Au) IV As above. Ovarian cancer, breast cancer, non-small cell lung cancer, AIDS-related Kaposi's sarcoma, cervical cancer, germ cell cancer and endometrial cancer Hypersensitivity, myelosuppression, peripheral neuropathy, myocardial infarction (uncommon), arrhythmias (uncommon), pulmonary toxicity (rare), radiation recall (rare), scleroderma-like skin changes (rare), Stevens–Johnson syndrome (rare), toxic epidermal necrolysis (rare), seizures (rare) and encephalopathy (rare).
1.08 Vinca alkaloids
Vinblastine Vinca alkaloid D (Au) IV Microtubule assembly inhibitor. Arrests cells in M phase. Hodgkin lymphoma, germ cell tumours, non-small cell lung cancer, bladder cancer and primary immune thrombocytopenia Neurotoxicity, myelosuppression, myocardial ischaemia (rare) and myocardial infarction (rare).
Vincristine Vinca alkaloid D (Au) IV As above. Lymphomas, acute lymphoblastic leukaemia, multiple myeloma, sarcoma, brain tumours, Wilms' tumour, neuroblastoma and primary immune thrombocytopenia Neurotoxicity, anaphylaxis (rare), myocardial ischaemia (rare) and myocardial infarction (rare).
Vindesine Vinka alkaloid D (Au) IV As above. Refractory metastatic melanoma, childhood acute lymphoblastic leukaemia, chronic myeloid leukaemia in blast crises, neuroblastoma, non-small cell lung cancer and breast cancer. Myelosuppression, neurotoxicity and paralytic ileus.
Vinflunine Vinca alkaloid D (Au) IV As above. Bladder cancer As per vinblastine.
Vinorelbine Vinca alkaloid D (Au) IV As above. Breast cancer and non-small cell lung cancer. As above.
1.09 Alkylating agents
Bendamustine Nitrogen mustard D (Au) IV Alkylates DNA. Chronic lymphocytic leukaemia, mantle cell lymphoma and non-Hodgkin's lymphoma. Myelosuppression, hypokalaemia and tachycardia.
Busulfan Dialkylsulfonate D (Au) IV, PO Alkylates DNA. Conditioning treatment before haematopoietic stem cell transplantation (high dose, IV), chronic myeloid leukaemia, myelofibrosis, polycythaemia vera and essential thrombocytosis Myelosuppression, seizures (high dose), tachycardia (high dose), hepatic sinusoidal obstruction syndrome (high dose), Addison-like syndrome (rare), pulmonary fibrosis (rare), cataracts (rare) and hepatitis (rare). Secondary malignancies.[1][160]
Carmustine Nitrosourea D (Au) IV Alkylates DNA. Anaplastic astrocytoma, glioblastoma multiforme andmycosis fungoides (topical) Myelosuppression, pulmonary fibrosis, pulmonary infiltrates, seizure, brain oedema, cerebrospinal leaks, subdural fluid collection, intracranial infection, hypotension (uncommon), tachycardia (uncommon), decrease in kidney size (reversible), uraemia (uncommon), kidney failure (uncommon), severe hepatic toxicity (rare), thrombosis (rare) and neuroretinitis (rare). Secondary malignancies.[1][160]
Chlorambucil Nitrogen mustard D (Au) IV Alkylates DNA. Lymphoma, chronic lymphocytic leukaemia andWaldenström's macroglobulinaemia Myelosuppression, hallucinations (rare), seizures (rare), sterile cystitis (rare), hepatotoxicity (rare), severe pneumonitis (rare), Stevens–Johnson syndrome (rare), toxic epidermal necrolysis (rare) and drug fever (rare). Secondary malignancies.[1][160]
Chlormethine Nitrogen mustard D (Au) IV, topical Alkylates DNA. Cutaneous T-Cell Lymphoma, metastatic carcinoma, leukaemias, lymphomas, polycythemia vera and bronchogenic carcinoma Thrombosis, myelosuppression (common), hyperuricaemia, erythema multiforme, haemolytic anaemia, nausea and vomiting (severe) and secondary malignancies.[160]
Cyclophosphamide Nitrogen mustard D (Au) IV Alkylates DNA. Breast cancer, lymphoma, acute lymphoblastic leukaemia, chronic lymphocytic leukaemia, sarcoma, multiple myeloma, Waldenström's macroglobulinaemia, systemic lupus erythematosus, glomerulonephritis, systemic vasculitis and Wegener's granulomatosis Myelosuppression, nausea and vomiting (>30%), haemorrhagic cystitis, heart failure (rare), pulmonary fibrosis (rare), hepatic sinusoidal obstruction syndrome (rare), water retention resembling SIADH (rare) and seizures (rare). Secondary malignancies.[160]
Dacarbazine Triazene D (Au) IV Alkylates DNA. Hodgkin lymphoma, metastatic malignant melanoma and soft tissue sarcoma Myelosuppression, agranulocytosis (uncommon), hepatic vein thrombosis (rare) and hepatocellular necrosis (rare). Secondary malignancies.[160]
Fotemustine Nitrosourea D (Au) IV Alkylates DNA. Metastatic malignant melanoma. Myelosuppression.
Ifosfamide Nitrogen mustard D (Au) IV Alkylates DNA. Sarcomas, testicular cancer and lymphomas. Myelosuppression, haemorrhagic cystitis, nephrotoxicity, neurotoxicity and cardiac toxicity (rare). Secondary malignancies.[160]
Lomustine Nitrosourea D (Au) PO Alkylates DNA. Glioma and medulloblastoma. Myelosuppression, pulmonary infiltration and fibrosis. Secondary malignancies.[160]
Melphalan Nitrogen mustard D (Au) IV, PO Alkylates DNA. Malignant melanoma of the extremities, multiple myeloma, conditioning treatment before haemopoietic stem cell transplant. Myelosuppression, pulmonary fibrosis and pneumonitis (uncommon), skin necrosis (uncommon), anaphylaxis, hepatic sinusoidal obstruction syndrome and SIADH. Secondary malignancies.[160]
Streptozotocin Nitrosourea D (Au) IV, PO Alkylates DNA. Pancreatic cancer and carcinoid syndrome. Nephrotoxicity, hypoglycaemia, myelosuppression, nausea and vomiting (>90%), jaundice and nephrogenic diabetes insipidus (rare).
Temozolomide Triazene D (US) PO Alkylates DNA. Anaplastic astrocytoma, glioblastoma multiforme, metastatic malignant melanoma Myelosuppression, Stevens–Johnson syndrome (rare), pneumonitis (rare) and hepatitis (rare).
1.10 Platinum compounds
Carboplatin Platinum complex D (Au) IV Reacts with DNA, inducing apoptosis, non-cell cycle specific. Ovarian cancer, lung cancer and squamous cell head and neck cancer Myelosuppression, nausea and vomiting (30-90%), peripheral neuropathy, ototoxicity, anaphylaxis, acute kidney failure (rare), haemolytic uraemic syndrome (rare) and loss of vision (rare).
Cisplatin Platinum complex D (Au) IV As above. Germ cell tumours (including testicular cancer), ovarian cancer, cervical cancer, small cell and non-small cell lung cancer, mesothelioma, squamous cell head and neck cancer, oesophageal cancer, gastric cancer, bladder cancer and osteosarcoma Nephrotoxicity, nausea and vomiting (30-100%), myelosuppression, electrolyte anomalies, peripheral neuropathy, ototoxicity and anaphylaxis, haemolytic anaemia (rare), optic neuritis (rare), reversible posterior leucoencephalopathy syndrome (rare), seizures (rare), ECG changes (rare) and heart failure (rare).
Nedaplatin [161] Platinum complex N/A IV As above. Non-small cell lung cancer, oesophageal cancer, uterine cervical cancer, head and neck cancer and urothelial cancer Nephrotoxicity, myelosuppression and nausea and vomiting (30-90%).
Oxaliplatin Platinum complex D (Au) IV As above. Colorectal cancer, oesophageal cancer and gastric cancer Myelosuppression, peripheral neuropathy, anaphylaxis, nausea and vomiting (30-90%), hypokalaemia, metabolic acidosis, interstitial lung disease (uncommon), ototoxicity (rare), reversible posterior leucoencephalopathy syndrome (rare), immune-mediated cytopenias (rare) and hepatic sinusoidal obstruction syndrome (rare).
1.11 Miscellaneous others
Altretamine Triazine D (Au) PO Unclear, reactive intermediates covalently bind to microsomal proteins and DNA, possibly causing DNA damage Recurrent ovarian cancer Myelosuppression, peripheral neuropathy, seizures and hepatotoxicity (rare).
Bleomycin Glycopeptide D (Au) IM, SC, IA, IV or IP Inhibits DNA and to a lesser extent RNA synthesis, produces single and double strand breaks in DNA possibly by free radical formation. Germ cell tumours, squamous cell carcinoma, pancreatic cancer, non-Hodgkin's, pleural sclerosing and Hodgkin's lymphoma. Pulmonary toxicity, hypersensitivity, scleroderma andRaynaud's phenomenon.
Bortezomib Dipeptidyl boronic acid C (Au) IV, SC Proteasome inhibitor. Multiple myeloma, mantle cell lymphoma and follicular lymphoma (orphan). Peripheral neuropathy, neutropenia, thrombocytopenia, anaemia, orthostatic hypotension, hepatitis (uncommon/rare), haemorrhage (uncommon/rare), heart failure (uncommon/rare), seizures (uncommon/rare), progressive multifocal leucoencephalopathy (PML) and hearing loss.
Dactinomycin Polypeptide D (Au) IV Complexes with DNA interfering with DNA-dependent RNA synthesis Gestational trophoblastic disease, Wilms' tumour and rhabdomyosarcoma Myelosuppression, anaphylaxis, radiation recall, hepatotoxicity and hepatic sinusoidal obstruction syndrome (common in Wilms' tumour).
Estramustine Nitrogen mustard and oestrogen analogue D (Au) PO Antimicrotubule and oestrogenic actions Prostate cancer. Cardiovascular complications, such as ischaemic heart disease, venous thromboembolism, congestive heart failure, pulmonary embolism, myocardial infarction and cerebrovascular failure.
Ixabepilone Epothilone B analogue D (US) IV Promotes tubulin polymerisation and stabilises microtubular function, causing cell cycle arrest at G2/M phase and subsequently induces apoptosis Locally advanced or metastatic breast cancer. Myelosuppression, peripheral neuropathy, myocardial ischaemia (uncommon/rare), supraventricular arrhythmia (uncommon/rare) and hypersensitivity reaction (uncommon/rare).
Mitomycin Aziridine D (Au) IV Cross-links DNA Anal and bladder cancer Myelosuppression, pulmonary toxicity and haemolytic uraemic syndrome (rare).
Procarbazine Methylhydrazine D (Au) IM, IV Inhibits DNA, RNA and protein synthesis. Glioma and Hodgkin's lymphoma. Myelosuppression, neurotoxicity, pulmonary fibrosis (uncommon/rare), pneumonitis (uncommon/rare), haemolysis (uncommon/rare) and hepatic dysfunction (uncommon/rare).
2. Targeted antineoplastics
2.1 Monoclonal antibodies
Alemtuzumab Protein B2 (Au) IV CD52 antibody induces apoptosis in the tagged cells. Chronic lymphocytic leukaemia Pancytopenia, pneumonitis, arrhythmias and hypersensitivity reactions (rare), autoimmune haemolytic anaemia (rare), autoimmune thrombocytopenia (rare) and progressive multifocal leucoencephalopathy (rare).
Bevacizumab Protein D (Au) IV VEGF inhibitor. Colorectal, breast, ovarian, renal cell and non-squamous non-small cell lung cancer and glioblastoma Hypertension, thromboembolisms, heart failure, bleeding, neutropenia, thrombocytopenia, GI perforation, fistula formation, hypertensive encephalopathy, pulmonary hypertension, reversible posterior leucoencephalopathy syndrome, nasal septum perforation and osteonecrosis of the jaw.
Cetuximab Protein D (Au) IV EGFR inhibitor. Squamous cell head and neck cancer or EGFR-positive and KRAS wild-type metastatic colorectal cancer. Infusion-related reactions, skin reactions, hypomagnesaemia, hypocalcaemia, hypokalaemia, blood clots, interstitial lung disease and aseptic meningitis.
Denosumab Protein X (US) SC RANKL inhibitor. Osteoporosis, including drug and cancer related osteoporosis,giant cell tumour of bone and hypercalcaemia of malignancies Hypercholesterolaemia, cataract, urinary retention, hypocalcaemia, osteonecrosis of the jaw and anaphylaxis.
Gemtuzumab ozogamicin [162] Protein D (US) IV CD33 antibody that induces apoptosis of the tagged cell. Acute myeloid leukaemia Hepatic veno-occlusive disease, myelosuppression, cytokine release syndrome, hypersensitivity and electrolyte anomalies.
Ibritumomab tiuxetan [163][164] Protein D (US) IV CD20 antibody bound with the radioactive isotope, 90Y, induces radiation-dependent cell lysis. Non-Hodgkin's lymphoma and follicular lymphoma. Thrombocytopenia, neutropenia, anaemia, hypotension and secondary malignancies.
Ipilimumab Protein C (Au) IV CTLA4 antibody that causes immune system-mediated lysis of the tagged cell Unresectable or metastatic malignant melanoma. Life-threatening immune mediated reactions and fever.
Ofatumumab [165][166][167] Protein C (US) IV Anti-CD20 antibody. Chronic lymphocytic leukaemia Neutropenia, pneumonia, infusion reactions, cytopenias
Panitumumab Protein C (Au) IV EGFR inhibitor. RAS (KRAS or NRAS) wild-type metastatic colorectal cancer Skin reactions, electrolyte anomalies, anaphylaxis and angiooedema (rare).
Pertuzumab Protein D (Au) IV HER2 inhibitor. HER2-positive breast cancer. Anaphylaxis, cardiac dysfunction and anaemia.
Rituximab Protein C (Au) IV Anti-CD20 antibody. CD20-positive B cell non-Hodgkin lymphoma, chronic lymphocytic leukaemia, rheumatoid arthritis, Wegener's granulomatosis and microscopic polyangiitis Infusion-related reactions, neutropenia, arrhythmias, infection, thrombocytopenia (uncommon), anaemia (uncommon), angina (uncommon), myocardial infarction (uncommon), heart failure (uncommon), haemolytic anaemia (rare), aplastic anaemia (rare), serum sickness (rare), severe skin conditions (rare), pulmonary infiltrates (rare), pneumonitis (rare), cranial neuropathy (vision or hearing loss; rare) and progressive multifocal leucoencephalopathy (rare).
Tositumomab [168][169] Protein X (US) IV Anti-CD20 antibody which is tagged with I131. Non-Hodgkin's lymphoma Grade 3-4 cytopenias, methaemoglobinaemia, acute myeloid leukaemia or myelodysplastic syndrome, anaphylaxis and hyperthyroidism.
Trastuzumab Protein B2 (Au) IV Anti-HER2 antibody. HER2-positive breast cancer, gastric cancer, pancreatic cancer (orphan) and gastro-oesophageal junction cancer. Cardiac dysfunction, infusion-related reactions, peripheral neuropathy and pulmonary toxicity (rare).
2.2 Tyrosine kinase inhibitor
Afatinib [170] Phenyl quinazolinamine D (US) PO EGFR, HER2 and HER4 inhibitor. Non-small cell lung cancer. Diarrhoea, hypokalaemia, interstitial lung disease and hepatotoxicity.
Aflibercept [171] Protein C (US) IV VEGF and PGF inhibitor. Colorectal cancer. Myelosuppression, hypertension, dehydration, blood clots, GI perforation and reversible posterior leucoencephalopathy syndrome (uncommon).
Axitinib [172] Indazole & pyridine analogue D (Au) PO Multikinase inhibitor. Renal cell carcinoma Hypertension, thyroid dysfunction, blood clots, electrolyte disturbances, GI perforation (rare), fistula formation (rare), reversible posterior leucoencephalopathy syndrome (rare) and polycythaemia (uncommon).
Bosutinib [173][174] Quinoline carbonitrile analogue D (Au) PO Bcr-Abl and SRc kinase inhibitor. Chronic myeloid leukaemia Diarrhoea, thrombocytopenia, neutropenia, hepatotoxicity, QT interval prolongation, kidney failure, pleural effusion, pericarditis (uncommon/rare), acute pancreatitis (uncommon/rare), GI haemorrhage (uncommon/rare), anaphylactic shock (uncommon/rare), acute pulmonary oedema (uncommon/rare), respiratory failure (uncommon/rare), pulmonary hypertension(uncommon/rare) and erythema multiforme (uncommon/rare).
Crizotinib [175][176][177]
[178][179]		 Aminopyridine D (US) PO ALK, Hepatocyte Growth Factor Receptor (HGFR, c-Met), and Recepteur d’Origine Nantais (RON) inhibitor. Non-small cell lung cancer Lymphopenia, neutropenia, hypophosphataemia, hypokalaemia, peripheral neuropathy, blood clots, QT interval prolongation, bradycardia, pneumonia, pneumonitis, kidney cyst, ARDS and liver failure.
Dasatinib Piperazine D (Au) PO BCR-ABL, SRC family, c-Kit, EPHA2 and PDGFR-β kinase inhibitor. Philadelphia positive chronic myeloid leukaemia and acute lymphoblastic leukaemia. Fluid retention, myelosuppression, haemorrhage, hypertension, electrolyte anomalies, cardiac dysfunction (rare), heart failure (rare), myocardial infarction, arrhythmia (rare), prolonged QT interval (rare), kidney failure (rare), hypersensitivity (rare) and hepatic failure (rare).
Erlotinib Quinazoline C (Au) PO EGFR inhibitor. Non-small cell lung cancer and pancreatic cancer. Skin reactions, diarrhoea, GI bleeds, anaemia, dehydration, interstitial lung disease (uncommon), hepatic failure (rare), hepatorenal syndrome (rare), GI perforation (rare) and ulcerative keratitis (rare).
Gefitinib Quinazoline C (Au) PO EGFR inhibitor. EGFR-mutation positive non-small cell lung cancer. Skin reactions, diarrhoea, dehydration, haemorrhage, interstitial lung disease (uncommon), pancreatitis (uncommon), hepatitis (uncommon), allergy (uncommon), hepatic failure (rare), toxic epidermal necrolysis (rare) and Stevens–Johnson syndrome (rare).
Imatinib Pyrimidine and piperazine. D (Au) PO Bcr-Abl kinase inhibitor. Philadelphia chromosome-positive acute lymphoblastic leukaemia, chronic myeloid leukaemia, GI stromal tumour and myelodysplastic/myeloproliferative diseases. Myelosuppression, fluid retention, GI bleeding, electrolyte anomalies, left ventricular dysfunction (uncommon), heart failure (uncommon), pulmonary oedema (uncommon), kidney failure (uncommon), angiooedema (rare), anaphylaxis (rare), GI perforation (rare), hepatotoxicity (rare), avascular necrosis (rare), myopathy (rare) and rhabdomyolysis (rare).
Lapatinib Quinazoline C (Au) PO HER2 inhibitor. HER2-positive breast cancer, stomach cancer (orphan) and oesophageal cancer (orphan). Diarrhoea, interstitial lung disease (uncommon), hepatotoxicity (uncommon) and anaphylaxis (rare).
Nilotinib Imidazole D (Au) PO Bcr-Abl kinase inhibitor. Chronic myeloid leukaemia. Myelosuppression, electrolyte disturbances, hyperglycaemia, prolonged QT interval (uncommon), peripheral arterial occlusive disease (uncommon), pancreatitis (uncommon), pleural effusion (uncommon) and pericardial effusion (uncommon).
Pazopanib Indazole D (Au) PO Multikinase inhibitor, including c-KIT, FGFR, PDGFR and VEGFR. Renal cell carcinoma and soft tissue sarcoma. Hypertension, QT interval prolongation, haemorrhage, blood clots, neutropenia, thrombocytopenia, neutropenia, thrombocytopenia, elevated thyroid-stimulating hormone, hypothyroidism, electrolyte disturbances, hypo- or hyperglycaemia, torsades de pointes (uncommon), heart failure (uncommon), hepatic failure (uncommon), GI perforation (uncommon), fistula formation (uncommon) and reversible posterior leucoencephalopathy syndrome (rare).
Ponatinib [180][181] Imidazopyridazine D (US) PO Multikinase inhibitor (BEGFR, PDGFR, FGFR, EPH receptors and SRC families of kinases, and KIT, RET, TIE2 and FLT3), that also inhibits T135I Bcr-Abl kinase. T135I positive Chronic myeloid leukaemia and Philadelphia chromosome positive acute lymphoblastic leukaemia. Hypertension, neutropenia, leucopenia, anaemia, thrombocytopenia, lymphopenia, pleural effusion, heart failure, peripheral neuropathy, haemorrhage, blood clots, pancreatitis and infection.
Regorafenib [182][183][184]
[185]		 4-phenoxypyridine D (US) PO Multikinase inhibitor for RET, VEGFR1, VEGFR2, VEGFR3, KIT, PDGFR-alpha, PDGFR-beta, FGFR1, FGFR2, TIE2, DDR2, Trk2A, Eph2A, RAF-1, BRAF, BRAFV600E, SAPK2, PTK5, and Bcr-Abl. Colorectal cancer and GI stromal tumours. Anaemia, lymphopenia, thrombocytopenia, electrolyte anomalies, hepatotoxicity, hypertension, hypothyroidism, neutropenia, myocardial ischaemia or infarction.
Ruxolitinib [186][187][188]
[189]		 Pyrimidinylpyrazole C (Au) PO JAK1 and JAK2 inhibitor. Myelofibrosis and pancreatic cancer (orphan). Anaemia and thrombocytopenia.
Sorafenib 4-phenoxypyridine D (Au) PO Multikinase inhibitor (including VEGF and PDGF receptor kinases). Renal cell carcinoma and hepatocellular carcinoma. Hypertension, skin reactions, bleeding, neutropenia, thrombocytopenia, lymphopenia, peripheral neuropathy, thyroid dysfunction, electrolyte anomalies, myocardial ischaemia or infarctions, heart failure (uncommon), GI perforation (uncommon), pancreatitis (uncommon), reversible posterior leucoencephalopathy syndrome (rare), hepatitis (rare), nephrotic syndrome (rare) and prolonged QT interval (rare).
Sunitinib Oxindole D (Au) PO Multikinase inhibitor (including VEGF & PDGF receptor tyrosine kinases) renal cell carcinoma, GI stromal tumour and pancreatic neuroendocrine tumour Neutropenia, thrombocytopenia, lymphopenia, hypertension, left ventricular dysfunction, heart failure, blood clots, thyroid dysfunction, electrolyte anomalies, pancreatitis (uncommon), hepatic failure (uncommon), prolonged QT interval (rare), torsades de pointes (rare), GI perforation (rare), fistula formation (rare), seizures (rare), reversible posterior leucoencephalopathy syndrome (rare), haemolytic uraemic syndrome (rare), thrombotic thrombocytopenic purpura (rare), nephrotic syndrome (rare), hypersensitivity (rare), angiooedema (rare), toxic epidermal necrolysis (rare) and Stevens–Johnson syndrome (rare).
Vandetanib[190] Quinazoline D (US) PO Tyrosine kinase inhibitor (TKI) with selective activity against RET, VEGFR-2 and EGFR Medullary thyroid cancer. Diarrhoea, hypertension, QT interval prolongation, depression, electrolyte anomalies, hypothyroidism and GI perforation (uncommon).
2.3 mTOR inhibitors
Everolimus Sirolimus analogue. C (Au) PO mTOR inhibitor. Renal cell cancer, pancreatic neuroendocrine tumour and breast cancer Pleural effusion, hyperglycaemia, hypercholesterolaemia, hypertriglyceridaemia, neutropenia, lymphopenia, thrombocytopenia, anaemia, bleeding, kidney failure, hypokalaemia, hypophosphataemia, pneumonitis, impaired wound healing (uncommon), anaphylaxis (rare) and angiooedema (rare).
Temsirolimus Sirolimus analogue. D (Au) IV mTOR inhibitor. Renal cell cancer and mantle cell lymphoma. Infusion reactions, impaired wound healing, hyperglycaemia, hypercholesterolaemia, hypertriglyceridaemia, neutropenia, lymphopenia, thrombocytopenia, anaemia, bleeding, kidney failure, hypokalaemia, hypophosphataemia, pneumonitis, bowel perforation (uncommon) and intracerebral bleeding and Stevens–Johnson syndrome (rare).
2.4 Retinoids
Alitretinoin 9-cis retinoic acid D (US) Topical Retinoic acid receptor (RAR) and retinoid X receptor (RXR) agonist. Kaposi's sarcoma. Oedema, rashes
Bexarotene[191] Phenethylnaphthalene X (US) PO, topical RXR agonist. Cutaneous T cell lymphoma Leucopenia, anaemia, lactic dehydrogenase increased, hypochromic anaemia, hyperlipidaemia, hypercholesteraemia, hypothyroidism, haemorrhage, hypertension and kidney dysfunction.
Isotretinoin 13-cis retinoic acid D (Au, topical), X (Au, oral) PO, topical RXR & RAR agonist. Neuroblastoma[192] andacne. Topical: Skin reactions, blood lipid anomalies, increased platelet count and osteoporosis.[193] Oral: Anaemia, Red blood cell sedimentation rate increased, thrombocytopenia, thrombocytosis, neutropenia, anaphylaxis, hypersensitivity, diabetes mellitus, hyperuricaemia, psychiatric disturbances (rare), convulsions (very rare), conjunctivitis, vasculitis (very rare), GI haemorrhage (very rare), hepatitis (very rare), erythema multiforme, Stevens–Johnson Syndrome, toxic epidermal necrolysis, arthritis (very rare), rhabdomyolysis and glomerulonephritis (very rare).[194]
Tamibarotene [195][196][197] Naphthalene N/A PO RAR agonist. Refractory acute promyelocytic leukaemia and Alzheimer's disease. Hypercholesterolaemia, hypertriglyceridaemia, gastrointestinal disturbances, liver damage, leucocytosis anddifferentiation syndrome.
Tretinoin all-trans retinoic acid D (Au, topical), X (Au, oral) PO, topical RXR & RAR agonist. Acne andacute promyelocytic leukaemia. Oral: Differentiation syndrome, hyperleucocytosis, elevated cholesterol and triglycerides, arrhythmias, pancreatitis, elevated liver enzymes, thrombosis, intracranial hypertension and pseudotumour cerebri (mainly in children), anxiety, depression and genital ulceration (rare). Topical: Erythema.
2.4 Immunomodulatory Agents (IMiDs)
Lenalidomide Thalidomide analogue X (Au) PO Numerous actions; anti-angiogenesis (via inhibition of VEGF release), anti-TNF, IL-6 and pro-IL-2, IFN-γ effects. Also stimulates T cells and apoptosis in cancer cells. Multiple myeloma Blood clots, neutropenia (dose-limiting), thrombocytopenia (dose-limiting), anaemia, infection, hypotension, hypokalaemia, hypothyroidism, Stevens–Johnson syndrome, toxic epidermal necrolysis, angioedema, pneumonitis, hepatotoxicity and secondary malignancies (mostly myelodysplastic syndrome and acute myeloid leukaemia).
Pomalidomide Thalidomide analogue X (US) PO As above. Multiple myeloma and systemic sclerosis (orphan). Neutropenia, anaemia, pneumonia, thrombocytopenia, hypercalcaemia, hyperglycaemia, kidney failure, lymphopenia, hyponatraemia, hypocalcaemia, hypokalaemia, peripheral neuropathy and thromboembolism.
Thalidomide Thalidomide X (Au) PO As above. Multiple myeloma, erythema nodosum leprosum and the following orphan indications: graft versus host disease, mycobacterial infection, recurrent aphthous ulcers, severe recurrent aphthous stomatitis, primary brain malignancies, HIV-associated wasting syndrome, Crohn's disease, Kaposi's sarcoma, myelodysplastic syndrome and haematopoietic stem cell transplantation. Peripheral neuropathy, depression, thromboembolism, bradycardia, orthostatic hypotension, leucopenia, hypothyroidism, thrombocytopenia (uncommon), Stevens–Johnson syndrome (rare), toxic epidermal necrolysis (rare), pneumonitis (rare), hepatotoxicity (rare) and hearing loss (rare).
2.5 Histone deacetylase inhibitors
Romidepsin [198] Depsipeptide D (US) IV Histone deacetylase inhibitor, hence inducing alterations in gene expression in the affected cells. Peripheral and cutaneous T cell lymphoma. Electrolyte anomalies, anaemia, thrombocytopenia, neutropenia, lymphopenia and ECG anomalies.
Valproate[Note 1] [199][200][201]
[202]		 Branched short-chain fatty acids. D (Au) PO, IV As above. Migraine prophylaxis, mania, epilepsy, fragile X syndrome (orphan), familial adenomatous polyposis (orphan) and the following off-label uses: cervical cancer, melanoma, mesothelioma, acute myeloid leukaemia and myelodysplastic syndrome. Hyperammonaemia, thrombocytopenia, polycystic ovaries, SIADH (uncommon), hepatic failure (rare), pancreatitis (rare), leucopenia (rare), neutropenia (rare), pure red cell aplasia (rare), agranulocytosis (rare), extrapyramidal syndrome (rare), reduced BMD with long-term use, pleural effusion (rare) and multiorgan hypersensitivity reaction (rare).
Vorinostat [203] Phenyloctanediamide D (US) PO As above. As per romidepsin. Thrombocytopenia, anaemia, QT interval prolongation and pulmonary embolism.
2.6 Other Agents
Anagrelide Imidazoquinazoline B3 (Au) PO Phosphodiesterase 3 inhibitor. Essential thrombocythaemia Fluid retention, palpitations, tachycardia, hepatotoxicity (uncommon), heart failure (uncommon), hypertension (uncommon), arrhythmia (uncommon), syncope (uncommon), cardiomyopathy (rare), cardiomegaly (rare), MI (rare), pulmonary hypertension (rare), interstitial lung disease (rare) and pancreatitis (rare).
Arsenic trioxide[Note 2] Arsenic compound X (Au) IV Not fully understood. Induces partial differentiation and promotes apoptosis of leukaemic cells and may also inhibit angiogenesis. Refractory or relapsed acute promyelocytic leukaemia. Orphan indications include: acute myeloid leukaemia, chronic lymphocytic leukaemia, malignant glioma, myelodysplastic syndrome, multiple myeloma, liver cancer and chronic myeloid leukaemia. Differentiation syndrome, hyperleucocytosis, neutropenia, thrombocytopenia, ventricular tachycardia, prolonged QT interval, torsades de pointes, complete atrioventricular block, peripheral neuropathy, hyperglycaemia, hypokalaemia, hypomagnesaemia, elevation of bilirubin or aminotransferases, hepatotoxicity and secondary malignancies.
Asparaginase
[Note 3]		 Protein D (Au) IM, IV Catalyses the conversion of the amino acid L-asparagine to aspartic acid and thereby reduces the availability of L-asparagine to leukaemic cells. Unlike normal cells, certain types of leukaemic cells do not synthesise L-asparagine, which is essential for cell growth and survival. Acute lymphoblastic leukaemia and lymphoblastic lymphoma. Allergic reactions, haemorrhagic and thrombotic events, uraemia, pancreatitis, hyperglycaemia, hyperammonaemia, acute kidney failure and diabetic ketoacidosis.
BCG vaccine
[Note 4]		 Protein B2 (Au) IB Live, attenuated Mycobacterium bovis, which produces a local inflammatory reaction, resulting in elimination or reduction of superficial tumour lesions of the bladder. Bladder cancer Cystitis, BCG infection and contracted bladder.
Denileukin diftitox [204][205][206]
[207]		 Protein C (US) IV Interleukin 2 combined with diphtheria toxin which binds to the interleukin receptor on immune cells and introduces the diphtheria toxin into the cell. Cutaneous T cell lymphoma and peripheral T cell lymphoma (orphan). Infusion reactions, hypocalcaemia, hypotension, thrombocytopenia, Acute renal insufficiency (uncommon/rare), Hyper/hypothyroidism (uncommon/rare), pancreatitis (uncommon/rare) and toxic epidermal necrolysis (uncommon/rare).
Vemurafenib Pyrrolopyridine D (Au) PO BRAF kinase inhibitor. BRAF kinase mutation V600E-positive Metastatic melanoma. Skin reactions, secondary malignancies (mostly squamous cell carcinoma), anaphylaxis (rare) and hypotension (rare).

Abbreviations/Acronyms:
IM - Intramuscular. IV - Intravenous. IA - Intra-arterial. SC - Subcutaneous. PO - Per os, oral. IP - Intrapleural. IB - Intrabladder. Preg. cat. - Pregnancy category. The preferred pregnancy category is Australian, but if it is unavailable the pregnancy category given is American.

Notes

edit
  1. ^ Its use in cancer treatment is purely investigational at this point in time
  2. ^ There is no INN for arsenic trioxide, just the USAN
  3. ^ There is no INN for asparaginase, only a USAN
  4. ^ There is no INN for BCG

Reference list

edit
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