ONCOLOGY - TREATMENT Flashcards
What is radiotherapy used for?
Primary curative oncology treatment, adjuvant therapy and palliative of cancer symptoms
It’s also, less commonly, used to treat non-malignant diseases e.g graves thyroiditis and keloid scarring
How does radiotherapy work?
Linear accelerator causes high speed particles to collide with a target inside the machine and photons are released and targeted to the patient. (Electrons and protons can be used but this is less common)
Indirect - Radiation contacts water which produces free radicals. Contact with nearby oxide produces superoxide radicals which cause damage to the cell
Direct - accumulation of double strand breaks lead to cell death.
Why are cancer cells more vulnerable to radiation than healthy cells?
They divide more often than normal thus their cell cycle repeats more frequently and they are therefore more vulnerable to damage by radiation
They also cannot repair damage as well as healthy cells
What is fractionation? Why is it important in radiotherapy?
When you distribute damage by breaking up the total dose of radiation
Important as not all cells are dividing at the same time so you need to repeat the process until all the cancer cells are destroyed
It also allows normal cells to recover in between treatment fractions (normal cells repair DNA damage better)
What are the different types of radiotherapy?
External bean radiotherapy
Brachytherapy
Internal
What is external beam radiotherapy?
The most common form of radiotherapy
An external source of ionising radiation is pointed at a particular part of the body
What is brachytherapy?
a form of radiation therapy where a sealed radiation source is placed inside or next to the area requiring treatment
Commonly used for cervix, prostate
What is internal radiotherapy?
Radiotherapy is administered orally or IV as isotopes.
E.g. oral iodine-131 therapy for thyroid cancer
For which cancers is radiotherapy curative on its own?
Prostate
Cervix
Vocal cord
Non-melanoma skin cancer
What is chemo radiation?
When they have chemotherapy at the same time as radiotherapy
What are the late side effects of radiotherapy?
Skin pigmentation changes
Pulmonary fibrosis
Infertility
Secondary cancers
What are radiotherapy-induced second malignancies?
What are the most common types
Cancer caused by previous radiotherapy
Most common cancers are AML< ALL and CML
What are the types of radioisotope therapy and their indications?
Iodine-131 for thyroid cancers
Strontium-89 and samarium-153 - metastatic bone cancer
Radium-223 for prostate cancer spread to bones
How long are radical radiotherapy treatments?
4-7 weeks
What are linear accelerators?
Machines that generate x-rays at high energies which enable administration of high doses of radiation to deep-seated tumours and minimise doses to the skin and subcutaneous tissue
What are the main groups of cytotoxic chemotherapy?
Alkylating agents
Platinum compounds
Antimetabolites
Anthracyclines
Topoisomerase inhibitors
Anti-microtubule agents
Tyrosine kinase inhibitors
Plant alkaloids aka mitotic inhibitors
Anti-tumour antibiotics
What are alkylating agents?
Anti-proliferative drugs that bind covalently with DNA via alkyl groups to form covalent bonds, causing single-strand or double- strand DNA breaks and cross-linking. This DNA is unable to complete normal cell division and so undergo cell arrest where it will be repaired or undergo apoptosis
What are the examples of alkylating agents?
Nitrosureas e.g. carmustine, lomustine, semustine, fotemustine and streptozotocin
Dacarbazine
Procarbazine
Cyclophosphamide
What are examples of platinum compounds used in chemotherapy?
Cisplatin
Carboplatin
Oxaliplatin
How do platinum compounds work for chemotherapy treatment?
Cross-link DNA strands, thereby inhibiting DNA synthesis and function. If the DNA is damaged enough, the cell will undergo apoptosis
What are antimetabolites?
Cytotoxic agents that structurally resemble naturally occurring purines and pyrimidines.
How do antimetabolites work for chemotherapy treatment?
They disrupt the pathway responsible for DNA synthesis by mimicking nucleobases or folic acid, and cause DNA replication and cell proliferation to come to a halt.
Medications that mimic purine include azathioprine and cladribine, while medications that mimic pyrimidine include cytarabine and 5-fluorouracil. Finally, there’s folic acid analogues like methotrexate.
Why are antimetabolites schedule dependant rather than dose dependant?
Because they generally act at the S phase of the cell cycle
What are examples of antifolates used in chemotherapy?
Methotrexate
Pametrexed
How do antifolates work?
antagonise the actions of folic acid which primary function is as a cofactor to various methyltransferases involved in serine, methionine, thymidine and purine biosynthesis. Consequently, antifolates inhibit cell division, DNA/RNA synthesis and repair and protein synthesis.
What are the subtypes of antimetabolites?
Antifolates
Anti pyrimidine
Arabinosides
Anti purines
What anthracyclines/anti-tumour antibiotics do we use for chemo?
Daunorubicin, doxorubicin, mitomycin and bleomycin
What are anthracyclines?
Drugs extracted from streptomyces species
How do anthracyclines work?
Intercalate with DNA causing ss and ds breaks
Generation of free radicals which can cause oxidative damage to cellular proteins
Topoisomerase 2 inhibition
What are examples of topoisomerase inhibitors used in chemo?
Topoisomerase I inhibitors include irinotecan, topotecan, and camptothecin
Topoisomerase II inhibitors include etoposide, doxorubicin, and epirubicin.
How do topoisomerase inhibitors work?
DNA cannot unwind so DNA replication is inhibited.
What are examples of vinca alkaloids?
Vincristine
Vindesine
Vinorelbine
Vinblastine
What are examples of taxanes?
Paclitaxel and docetaxel
What is tubulin?
The basic subunit of microtubules, which have many important, diverse roles in cell function including maintenance of cell shape, mitosis, meiosis, secretion, intracellular transport and axonal function.
How do vinca alkaloids work?
A type of antimicrotubule agent - Inhibit microtubules formation which disrupts M phase, causing cell arrest
How do taxanes work?
A type of antimicrotubule agent - Bind to microtubules already formed and inhibit their breakdown, which means the M phase doesnt complete and you get cell arrest
What are examples of tyrosine kinase inhibitors used in chemotherapy?
Imatinib - CML and GI stromal tumours
Erlotinib - non-small cell lung cancer
Sunitib - renal cancer
Sorafenib - renal cancer
Lapatinib - breast cancer
How do tyrosine kinase inhibitors work?
phosphorylate specific amino acids on substrate enzymes, which subsequently alter signal transduction leading to downstream changes in cellular biology
For which cancers are hormone therapy particularly effective for?
Breast and prostate cancer
Outline the difference in hormone synthesis between pre- and post-menopausal women
premenopausal women, oestradiol is primarily pro- duced from the ovaries, whereas in postmenopausal women peripheral conversion of adrenal androgens by aromatase within peripheral fat pre- dominates.
How is hormonal therapy achieved in men and pre-menopausal women?
Castration