Chemotherapy
These drugs aim to kill fast dividing cells which is a hallmark of malignant cells. They are given at interval (cycles of treatment) to allow the recovery of normal tissue.
Inhibitors of DNA replication
One classic hallmark of cancer is non-controlled proliferation, which requires high rates of DNA synthesis. Therefore, the majority of drugs are designed to target this process, stopping cancer progression.
Covalent DNA binders
Compounds which have an electrophilic centre, allowing it to form covalent bonds with nucleophilic bases
Nitrogen Mustards – Cyclophosphamide, chlorambucil
These are very reactive and form a positive ion which allows them to bind the oxygen/nitrogen in bases, to cause crosslinking of the DNA.
They usually lead to bone marrow suppression and can cause secondary cancer
Melphalan and Chlorambucil are used for chronic lymphocytic leukaemia (+lymphomas)
Side Effects
Myelosuppression (neutropenia)
SIADH
Haemorrhagic cystitis (as broken down to irritant acrolein) – this is prevented with MESNA, which binds and inactivate acrolein
Transitional Cell Carcinoma (usually in the bladder)
Nitrosoureas – Lomustine, carmustine
These are also alkylating agents which work similarly to the nitrogen mustards to crosslink DNA
They can cross the BBB and so are useful in treating brain tumours and Hodgkin’s disease
Side Effects
Myelosuppression
Platinium Compounds – Cisplatin
This drug contains platinum which forms crosslinks with the DNA between neighboring bases.
This causes bending of the DNA helix which inhibits DNA replication and transcription.
It is used to treat testicular, ovarian and bladder cancers.
Side Effects
Nephrotoxicity
Ototoxicity
Peripheral Neuropathy
Hypomagnesiumaemia
Anti-tumour drugs
Anthracyclines – Doxorubicin, Actinomycin
These drugs non-covalently intercalate in the DNA and block synthesis of DNA and RNA.
They also generate free radicals which results in strand breakage
Side Effects
- Doxorubicin can cause dilated cardiomyopathy leading to heart failure.
Mitomycin
This is an alkylating agent that must be activated intracellularly
It causes free radical formation which causes DNA strand breaks
Side Effects
Myelosuppression (condition where bone marrow activity is decreased)
Bleomycin
This intercalates in the DNA grooves and generates radicals to cause strand breaks
Side Effects
Pulmonary fibrosis of the lower lobes
Anti-metabolites
Methotrexate
This is an inhibitor of dihydrofolate reductase which stops synthesis of folic acid
The starting dose is 7.5mg weekly and it is only given in 2.5mg tablets
Check FBC, U&Es + LFTs before starting and then monitor weekly until stable, then every 2-3 months
Must take folic acid 5mg once weekly, usually more than 24 hours after methotrexate dose
NB – In order to counter the side effects of this, patients are given Leucovorin/Folinic acid, a folic acid precursor with can be converted to tetrahydrofolate without DHFR enzyme. This helps target the toxicity to cancerous cells + used to “rescue” from methotrexate toxicity
Side Effects
Myelosuppression
Mucositis
Liver/Lung fibrosis
Cannot be given with trimethoprim or co-trimoxazole due to bone marrow aplasia
Women should avoid pregnancy for 6 months after treatment
6-Mercaptopurine
This is a purine analogue that is activated by HGPRTase
It decreases purine synthesis stopping proliferation of the cancerous cells.
Side Effects
Myelosuppression
Mucositis
Dermatitis
5-Fluorouracil
This is a pyrimidine analogue which inhibits the thymidylate synthetase enzyme
Stops the production of thymine which is needed to synthesis DNA, so during mitosis cell apoptoses
Classically used in treatment of colorectal cancer with leucovorin to protect normal cells
Side Effects
Myelosuppression
Cytarabine
This is a pyrimidine antagonist which interferes with DNA polymerase
This stops DNA synthesis at the S-phase of the cell cycle
Side Effects
Myelosuppression
Ataxia
DNA topoisomerase inhibitors
Etoposide
This is an inhibitor of DNA topoisomerase type II, used commonly in testicular tumours
Topotecan, irinotecan
These are inhibitors of DNA topoisomerase type I
Irinotecan is classically used for treating metastatic colon cancer with 5-FU and leucovorin
Side Effects
Myelosuppression
Inhibitors of mitosis
These drugs inhibit formation of the spindle assembly made of microtubules.
The microtubules are made of tubulin dimers which are arranged in filaments.
The free dimers are added to the growing filament in a reversible reaction (kept in equilibrium)
Taxanes – Paclitaxel, docetaxel
They shift the equilibrium towards building more microtubules
This gives abnormal microtubule formation causing cell arrest in mitosis
Side Effects
Neutropenia
Peripheral neuropathies
Vinca alkaloids – Vinblastine, vincristine
These bind free tubulin dimers to prevent microtubule assembly
Used for treating Hodgkin’s + non-Hodgkin lymphomas and given IV
Side Effects
Vincristine – Peripheral neuropathy, paralytic Ileus
Vinblastine – Myelosuppression
Small molecule inhibitors
Imatinib
This is a tyrosine kinase inhibitor specific for the Bcr-Abl oncoprotein
It is specific for chronic myeloid leukaemia, due to the Bcr-Abl chromosome translocation which gives the Philadelphia chromosome
Also used for GI tumours displaying tyrosine kinase c-kit.
Erlotinib
This inhibits the tyrosine kinase domain found in the epidermal growth factor receptor
Monoclonal antibodies
These are antibodies against a specific tumour antigen which slows tumour either by enhancing host immunity or is conjugated with chemotherapy to provide more targeted treatment. All are given IV.
Rituximab
This is mAb against CD20 on B cells, used in Hodgkin’s and autoimmune conditions
Cetuximab
This is a mAb that binds epidermal growth factor receptor (EGFR)
It prevents growth factor from binding and used in colorectal cancers with 5-fluorouracil
Alemtuzumab
Binds CD52 on lymphocytes, targeting T cells for destruction
It is used to treat various leukhaemias and lymphomas due to widespread attack on lymphocytes
Trastuzumab (Herceptin)
This is a mAb against epidermal growth factor 2 (HER2) in breast cancer cells
It is used to treat HER2+ breast cancers after the first line therapy has failed
Side Effects
Chills and fever
Risk of heart problems so not used in angina/heart patients
Bevacizumab (Avastin)
This is a mAb which inhibits VEGF, a key factor which stimulates angiogenesis
Side Effects
Interferes with wound healing
Disclaimer
The intended purpose of this website is to be used as a resource for revision for exams. It should not be used as a guideline or reference for clinical practice/decision making or by patients looking for medical information or advice. In2Med takes no responsibility for any loss or damaged resulting from the use of information from this website.
