Cancer Chemotherapy Flashcards
What are the limitations of anti-cancer therapy/
- cancers are good at evading the immune response
- cancer originates from the body’s own cells and so the body has poor defences
- cancer cells have the same biochemistry as normal body cells which makes targeting difficult
What are the 3 main approaches to dealing with cancer?
- surgical excision
- radiotherapy
- chemotherapy
What are the 4 traditional agents used for cancer?
- alkylating agents
- antimetabolites
- cytotoxic antibiotics
- plant derivatives
Describe the mechanism of action of alkylating agents
- can form covalent bonds with nucleophilic substances in the cancerous cell
- bifunctional and causes intrastrand cross-linking of DNA
What are the 6 major groups of alkylating agents and some examples?
- nitrogen mustards (eg. cyclophosphamide)
- ethylenimines (eg. thiotepa)
- alkylsulphonates (eg. busulphan)
- hydrazines and triazines (eg. temozolomide)
- nitrosoureas (eg. lomustine/carmustine)
- platinum based compounds (eg. cisplatin)
What are the 3 major groups of antimetabolites and examples?
- antifolates (eg. methotrexate)
- antipyrimidines (eg. 5-FU, gemticibane)
- antipurines (eg. mercaptopurine, thioguanine)
What are some examples of cytotoxic antibiotics?
- anthracyclines
- dactinomycin
- bleomycin
- mitomycin
What are the 2 mechanisms of action of plant derivatives?
- spindle poisons: affect microtubule function and prevent mitotic spindle formation
- top I/II inhibitors
What are examples of plant derivates?
- spindle poisons:
- vinca alkaloids eg. vincristine, vinblastine
- taxanes eg. paclitaxel, doxetaxel
- top I/II inhibitors:
- camptothecins eg. irinotecan (top I)
- etoposide eg. DNA binding (top II)
What are the drawbacks of chemotherapy?
- it targets cell proliferation not invasiveness/metastasis
- non-specific cell killers so can kill healthy cells
- development of resistance
- leaves remaining cells
- side effects which can affect body systems that have high cell growth rate
- side effects which are drug specific
- side effects often post treatment
- patient non-compliance due to side effects (not completing therapy)
Describe what tumour lysis syndrome is
- acute side effect of chemo
- metabolic emergency
- due to rapid cell lysis and large amounts of cell matabolites in blood
- characterised by hyperuricaemia, hyperphosphataemia, hyperkalaemia, hypocalcaemia
- if left untreated can lead to acute renal failure, cardiac arrest and death
How would you manage and prevent tumour lysis syndrome?
- manage it by monitoring and responding to deranged urea and electrolytes/fluid balance: may need dialysis
- prevent by risk assessing patient prior to chemotherapy
Describe the side effect of chemotherapy on the bone marrow
- myelosuppression; reduced production of cells that provide immunity, oxygen transport and clotting
- only actively dividing cells in bone marrow
- cells with shorter life span more affected
How would you manage and treat myelosuppression?
- monitor full blood count prior to and then daily during treatment cycles
- occasional use of recombinant human granulocyte- colony stimulating factors to reduce incidence/duration of myelosuppression
What are the GI side effects of chemotherapy?
- nausea and vomiting
- loss of appetite
- constipation (due to reduction is gastric motility/fluid intake/activity)
- diarrhoea (can cause severe dehydration and electrolyte disturbances)
- ulceration, dry mouth, pain, taste alterations
What are some examples of emetogenic chemotherapy agents?
- highly emetogenic: cisplatin
- moderately emetogenic: doxorubicin
- midly emetogenic: etoposide
How would you treat nausea/vomiting due to chemo?
- pre-treatment low dose benodiazepine eg.lorazepam
- steroids eg. dezamethasone
- anti-emetics eg. metoclopramide
What are other specific side effects of chemotherapy?
- fatigue
- body-image side effects (weight gain/loss, hair loss, intervention wounds)
- peripheral neuropathy (counsel patient, analgesia for nerve pain)
- altered renal function
- infertility
- secondary malignancy
What is the treatment for specific target of B cell lymphomas?
- rituximab
- targets a B cell surface protein
What is the treatment for target of HER1/ERBB2 in breast cancer?
- trastuzumab (herceptin)
- targets epidermal growth factor receptor 2 (HER2)
What is the choice of treatment for chronic myeloid leukaemia?
- imatinib (Gleevac)
- inhibits bcr-abl gene signalling pathways
What are the components of genetic medicine?
- genomic/genetic testing
- proteomic profiling
- metabolomic analysis
What are the 4Ps of personalised medicine?
- predictive
- personalised
- preventative
- participatory
Describe personalised medicine treatment of lung cancer
- if activating mutation on EGFR, given erlotinib
- BUT if activating mutation on KRAS not given
- if fusion ALK rearrangement, given crizotinib
Describe personalised medicine treatment of colorectal cancer
- cetuximab: anti-EGFR monoclonal antibody therapy
- if no mutation on KRAS/NRAS: cetuximab plus chemo (RAS mutation predicts lack of response to therapy)
Describe personalised medicine treatment on melanoma
- vermurafenib: inhibits mutated B-Raf (gene that leads to tumour growth)
- c-KIT mutations: imatinib
Describe personalised medicine treatment of high grade glioblastomas (brain tumours)
- temozolomide: alkylating agent (first line)
- increases methylation of MGMT promoter gene
- DNA repair enzyme that repairs damage caused by chemotherapy alkylating agents of cancer cells
- decreases expression of MGMT increasing survival of patients
Describe personalised medicine treatment of gastric tumours
- trastuzumab: anti-Her2 (and cisplatin and more)
- for tumours expressing high levels of HER2
- if c-KIT mutation in GISTs: imatinib used
Describe personalised medicine treatment of soft tissue and bone tumours
- FISH testing to complement morphological diagnosis for soft tissue sarcomas
- Ewing’s sarcomas
- alveolar rhabdomyosarcomas
- leiomyosarcomas
- fibromyxoid sarcomas
Describe personalised medicine treatment for thyroid tumours
- BRAF mutation analysis to aid pathological diagnosis
- BRAF mutation associated with aggressive tumour phenotype and higher risk of recurrent and perisistent disease
Why can pharmacogenetic testing be useful for treatment for cancer?
- germline variants in dihydropyrimidine dehydrogenase (DPYD) gene can confer increased risk of severe toxicity when patient is treated with
- flurorpyrimidines, capecitabine or 5-FU
Describe immunotherapy of cancer
- nivolumab is fully human IgG4 PD-1 immune checkpoint inhibitor antibody
- PD-1/PDL-1 signalling axis blockade (melanoma, specific lung cancer NSCLC)
- ipilimumab: anti-CTLA-4 antibody (metastatic melanoma)
