Session 10 Chemotherapy Flashcards
Examples of tumours that have highly sensitive chemo sensitivity? i.e. we only need to give chemo to treat
Lymphomas Germ cell tumours Small cell lung Neuroblastoma Wilm’s tumour
Examples of tumours that have modest sensitivity chemo sensitivity? i.e. can’t use chemo alone - combine with radiotherapy or surgery
Breast Colorectal Bladder Ovary Cervix lung
Examples of tumours that have low sensitivity chemo sensitivity? i.e. not very responsive to chemo
Prostate
Renal cell
Brain tumours
Endometrial
How do alkylating agents work?
Impair DNA replication
How do antimetabolites work?
5-fluorouracil (5-FU)
Methotrexate
Impair DNA synthesis
5-FU
* inhibits thymidylate synthase enzyme
Methotrexate
* inhibits dihydrofolate reductase so that purine’s can’t be made
Spindle poisons mode of action?
Once chromosomes are aligned at metaphase plate, spindle microtubles depolymerize, moving sister chromatids toward opposite poles
Nuclear membrane re-forms and cytoplasms device
Taxoids
* promote assembly of spindle and prevent disassembly
= cells are too rigid to divide
Vinca alkaloids
* Prevent spindle formation
How do microtubule binding agents work?
They disrupt microtubule dynamics In 2 ways:
Inhibit polymerisation
Stimulate polymerisation and prevent depolymerisation
What is the fractional cell kill hypothesis?
fractional kill hypothesis states that a defined chemotherapy concentration, applied for a defined time period, will kill a constant fraction of the cells in a population, independent of the absolute number of cells.
we basically use it to work out how often to give chemotherapy
cells of bone marrow - recover more quickly
need an overall reduction of tumour cells whilst minimising the reduction of bone marrow cells
Alkylating agents are vulnerable to resistance. How does this come about?
- decreased entry or increased exit of agent
- inactivation of agent in cell
- Enhanced repair of DNA lesions produced by alkylation
What is the predicted response (within the same cancer) based on?
- performance score
i. e. someone that is bed bound will have a performance score of 4 whilst someone who is fit and healthy will have one of 0 - clinical stage
- prognostic factos or score (involves biological factors)
- molecular or cytogenetic markers
What are two types of IV pumps used for chemotherapy?
PICC line
Hickman line
What are some side effects of chemotherapy?
mucosistis (can involve whole length of gut) nausea and vomiting diarrhoea cystitis sterility myalgia neuropathy alopecia pulmonary fibrosis cardiotoxicity renal faliure myelosuppression phlebitis
What are some adverse effects that are due to the effect of treatment on the tumour?
Acute renal failure
* hyperuricaemia caused by rapid tumour lysis leads to precipitation of urate crystals in renal tubules
GI perforation at site of tumour - reported in lymphoma
DIC
* acute myeloid leukaemia
Describe the pattern of vomiting (emesis) that can occur due to chemotherapy
acute phase = 4-12 hours
delayed onset = 2-5 days later
chronic phase = can persist up to 14 days
What are some local and general problems that involve the skin due to chemotherapy side effects?
from bleomycin..
from busulphan, doxorubicin, cyclophosphamide, actinomycin D..
local
- irritation and thrombophlebitis of veins
- extravasation
general
- from bleomycin (treatment)
- hyperkeratosis = thickening of the stratum corneum
- hyperpigmentation
- ulcerated pressure sores
- busulphan, doxorubicin, cyclophosphamide, actinomycin D
- hyperpigmentation
Where is mucositis most commonly worst in the body?
What does it present as?
oropharynx
sore mouth
diarrhoea
GI bleed
Which chemo drugs can cause a) cardio-myopathy and b) arrhythmias
a) doxorubicin or high dose cyclophosphamide
b) cyclophosphamide or etoposide
Which chemo drugs can cause lung toxicity?
bleomycin - pulmonary fibrosis
mitomycin C, cyclophosphamide, melphalan, chlorambucil - pulmonary fibrosis
drugs need to be altered for the individual patient based on what?
their surface area and/or BMI
drug handling ability (liver function, renal function etc)
general wellbeing (performance status and comorbidity)
treatment phasing needs to take into account the balance between what?
growth fraction
the ‘cell kill’ of each cycle of the chemotherapy regimen
marrow and GI tract recovery before next cycle
how tolerable the regimen is - both short term organ toxicity and physical side effects and long term damage causing late effects
What causes variability (of chemo and pharmacokinetics)?
give examples of each
abnormalities in:
- absorption: N+V, compliance, gut problems
- distribution: weight loss, reduced body fat, ascites
- elimination: liver or renal dysfunction, other meds
- protein binding: low albumin, other drugs
What are some important drug interactions of chemotherapy?
Vincrisitine + itraconazole = leads to more neuropathy
Capecitabine (oral 5-FU) + warfarin
Capecitabine + St Johns Wort or grapefruit juice
methotrexane - need to be cautions with penicillin and NSAIDS
How do we monitor the response of the cancer?
radiological imaging
tumour marker blood tests
bone marrow / cytogenetics
How do we monitor drug levels of methotrexane?
methotrexane drug assays taken on serial days to ensure clearance from the blood after folinic acid rescue
How do we check / monitor for organ damage?
creatinine clearance
echocardiogram
What is the aim of neoadjuvant chemotherapy?
given before surgery or radiotherapy for the primary cancer
what is the aim of adjuvant chemotherapy?
given after surgery to excise the primary cancer, aiming to reduce relapse risk e.g. breast cancer
what is the aim of palliative chemotherapy?
to treat current or anticipated symptoms without curative intent
what is the aim of primary chemotherapy?
1st line treatment of cancer (curative intent aiming for remission)
what is the aim of salvage chemotherapy?
chemotherapy for relapsing disease
