CANCER- MELANOMA Flashcards
There are two types of non-melanoma skin cancers, what are these?
Basal Cell carcinoma
Squamous cell carcinoma
Where is melanoma commonly found in women and men?
Men: backs and faces
Women: arms and legs
We use the ABCDEF system to identify melanomas. What does this stand for?
A: Asymmetrical B: Border C: colour (colour varies throughout) D: Diameter (larger than a pencil eraser) E: Elevation off the skin F: Funny mole
What are the risk factors for melanoma?
Sun exposure: Exposure to intermittent intense sun is more of a risk than prolonged exposure to UV radiation. Blistering sun burn in childhood a risk!!
Number of Moles
Skin type: Fair haired pale skin more likely
Family history
What does diagnosis of Melanomas involve?
patients usaully present with a changing or enlarging or irritating lesion
Mole examined under a dermascope
Excisional biopsy done to remove whole lesions
Histopathology: to determine stage and type of melanoma
Physical examination: lymphadenopathy (see if its spread to lymph nodes)
How do we treat stage 0/1/2/3 melanoma tumours?
Excision of the tumour followed by wide local excision to remove a good margin of the healthy tissue
How do we treat stage 4 melanoma tumours?
these are advanced tumours and are resectable (i.e. they can’t be cut out)
We treat with chemotherapy
Can use biological therapies: ipilimumab, vemurafenib
What is the prognosis with Advanced/ unresectable melanoma (stage 4)?
10 year survival is under 10%
Ipilimumab was the first agent to show an increase in overall survival in advanced/ unresectable malignant melanomas. What is this?
A recombinant human monoclonal antibody that will bind to CTLA-4 and block its interaction with its ligands CD80 and CD86.
It is recommended for use after a previous therapy has been tried (e.g. chemotherapy drug Dacarbazine) as its the most expensive cancer drug
Ipilimumab works by blocking CTLA-4. Its mechanism of action is INDIRECT possibly through T cell mediated anti tumour responses. What does this mean?
CTLA-4 is a molecule that serves as an immune checkpoint that results in down regulation of T-cell activation. This therefore prevents the immune system attacking cancer cells.
By blocking CTLA-4’s action, Ipilimumab stimulates the anti-tumour T cell response and lots of T cells are produced through unrestrained T cell proliferation
Remember: Ipilumumab blocks CTLA-4’s action which TURNS T CELLS ON
It therefore has an indirect action: it doesn’t kill the cell directly but makes the immune system do it!!
What are the side effects of Ipilumumab??
Diarrhoea Rash Pruritus Fatigue Nausea & vomitting Decreased appetite Abdominal pain
Advanced/ unresectable melanoma (stage 4) can be treated using Dacarbazine. what is this?
Chemotherapy agent
A DNA alkylating drug
No significant effect on overall survival
What drug can be used in patients that have the BRAF V600 gene mutation?
Vemurafenib
Its a BRAF (a tyrosine kinase) inhibitor
Its an oral drug
Vemurafenib is a GOOD drug in Malignant melanoma treatment.
Around 90% of patients have tumour regression quickly when treated with this drug!
Overall median survival is 15 months
Vemurafenib is not very well tolerated by patients as it has A lot of side effects.
What are the side effects of Vemurafenib? Try and list 6!!
Fatigue Joint Pain (patients may need pain killers) Rash (patients may need emollient, antihistamine or painkillers) Sensitivity to the sun Nausea Alopecia Pruritus (itching) Headache
Vemurafenib causes sensitivity to the sun. What should we advise patients do about this?
SPF 30-50 suncream needed in ALL WEATHERS (so even when its cloudy!)
wear long sleeves
Apply a UV resistant film to your windows
Really decreases QoL :(
Whats the strange side effect that Vemurafenib can produce?
Can actually induce a minor form of skin cancer: Cutaneous squamous cell carcinoma
They can be easily treated by surgical removal but patients should be advised to look out for and new/ changing skin lesions!
Vemurafenib is advised by NICE for patients with Malignant Melanomas who have the BRAF V600 mutations.
It has many drug interactions as its metabolised by the Cytochrome P450 enzymes
Dabrafenib is a BRAF inhibitor like Vemurafenib.
It has similar efficacy to Vemurafenib.
Its advantage is that it is better tolerated.
What are its side effects? (hint: 5 are the same as Vemurafenib, 2 new ones)
Fatigue Joint pain Rash Nausea Headache
Diarrhoea
FEVER- Patients should report temperatures over 38.
Dabrafenib has a slightly unusual side effect like Vemurafenib. What is this?
That is can actually cause a minor form of skin cancer: Cutaneous squamous cell carcinoma.
Patients should check for it, but it can be easily treated with surgery
Whats the very rare (1%) side effect that can be caused by Dabrafenib?
UVEITIS (swelling in the eye)
Can damage vision if its not treated
patients need to report blurry vision, eye redness or irritation
What route of administration are Vemurafenib and Dabrafenib?
ORAL (tablets
Vemurafenib: taken twice a day WITH food
Dabrafenib: taken twice a day WITHOUT food (empty stomach)
How does Pembrolizumab, a new drug, work?
It is an anti- PD-1 (programmed cell death receptor inhibitor)
Its a humanised monoclonal antibody
Its given by IV infusion
It blocks the interaction between PD-1 (a programmed cell death receptor) and its ligands: PD-L1 and PD-L2
By doing this: it takes the breaks off the immune system (see notes)
When is Pembrolizumab indicated for treatment of skin cancer?
For advanced Malignant melanoma following therapy with either ipilimumab or one of the BRAF inhibitors (Vemurafenib or Dabrafenib)
Its doesn’t have a UK license but it available under the UK Early Access to Medicines Scheme!
What are the side effects of Pembrolizumab?
Fatigue Cough Nausea Pruritis (itching) Rash Decreased appetite Constipation Diarrhoea
