Chemotherapy Flashcards
What is meant by the fractional cell kill hypothesis?
Chemotherapy is given in fractioned doses to target rapidly dividing cells. The following dose should be given so that only bone marrow cells have had chance to recover, resulting in the tumour cell burden decreasing with each bolus.
Which tumours are highly sensitive to chemotherapy?
Lymphoma Germ cell tumour Small cell Neuroblastoma Wilms tumour
Which tumours have a modest sensitivity?
Breast Colorectal Bladder Ovary Cervix
Which tumours have low sensitivity?
Prostate
Renal cell
Brain tumour
Endometrial
Where can cytotoxic agents exert their effects?
Antimetabolites
Alkylating agents
Intercalating agents
Spindle poisons
How do platinum agents exert there effects?
Form inter and intrastrand adducts, leading to inhibition of DNA synthesis.
DACH platinum adducts are bulky and thought to be more effective in inhibiting DNA synthesis.
How does 5-fluorouracil act as an antimetabolite?
It inhibits TS (thymidylate synthase) and prevents production of dTMP.
How does methotrexate work as a antimetabolite?
It inhibits dihydrofolate reductase and therefore prevents purine synthesis.
What are the spindle poisons and how do they exert their mechanism of action?
Taxoids- promote assembly and prevent disassembly of microtubules.
Vinca alkaloids prevent spindle formation of microtubules.
What mechanisms of resistance can cancer produce towards alkylating agents?
Decreased entry/increased exit of agent - active pump
In activation of agent within cell
Enhanced repair of DNA lesions
The predicted response of cancer is different between individuals due to?
Performance score
Clinical stage
Prognostic factors/score
Molecular or cytogenetic markers
Name some of the common side effects of chemotherapy
Alopecia Pulmonary fibrosis Cardiotoxicity Renal failure Myelosuppression Phlebitis Neuropathy Myalgia Sterility Cystitis Diarrhoea N and V Mucostitis
What are the patterns of vomiting and how is it thought to be triggered?
Multifactorial but direct action of chemotherapy drugs on the central chemoreceptor trigger zone.
Acute phase: 4-12 hours
Delayed onset: 2-5 days
Chronic phase: >14 days
With bleomycin, what skin ADRs can occur?
Hyperkeratosis
Hyperpigmentation
Ulcerated pressure sores
With busulphan, doxorubicin, cyclophosphasmide and actinomycin D what skin toxicity can occur?
Hyperpigmentation
What is mucositis and how may it present?
GIT epithelial damage and can affect part or whole tract.
Presents as sore mouth/throat, diarrhoea, GI bleed.
Commonly worst in oropharynx and may present with oral candidiasis.
Which drugs cause cardiomyopathy ?
Doxorubibicin
High dose cyclophosphamide
mortality 50%
Which drugs cause arrhythmias?
Cyclophosphamide
Etoposide
Which drugs can give lung toxicity (pulmonary fibrosis)?
Bleomycin Mitomycin C Cyclophosphamide Melphalan Chlorambucil
Why does chemotherapy need to be prescribed by specialists?
Narrow therapeutic index
Significant side effects
Dose needs to be altered based on surface area,BMI, drug handling ability, general wellbeing (performance status and comorbidities)
Treatment phasing needs to account for growth fraction, cell kill of each cycle, marrow and GI recovery, tolerability (organ damage and physical side effects in short and long term)
How are chemotherapeutics monitored?
Imaging
Response to treatment:
Tumour markers
Bone marrow/cytogenetics
Drug assays
Organ damage - creatinine damage and echocardiogram
What are some of the most adverse effects?
Acute renal failure - hyperuricaemia leads to urate crystals in tubules
GI perforation at site of tumour - reported in lymphoma
DIC - onset within few hours for AML
What is the local effects of skin toxicity with chemotherapy?
Irritation and thrombophlebitis
Extravasation
What is haematological toxicity important ?
Most frequent dose limiting
Most frequent cause of death
Different agents with variable effects on degree and lineage
