VP L5 Malignant melanoma Flashcards
3 main types of skin cancer
malignant melanoma
non-melanoma cancers (basal cell carcinoma/squamous cell carcinoma)
Risk factors for MM (4)
sun exposure - intense intermittent exposure
number of moles
fair skin
family history
pt usually presents with
changing/enlarging/irritating lesion
What is the process of examination
dermascope,
excisional biopsy
histopathology
physical examination - lyphadectomy, hepatomegaly or other suspect lesions (looking for mets)
Who is suitable for surgery
stage 0-3 (over 50% of stage 3 tumours reoccur)
stage four tumours treated by ~(2)
chemo
biological therapies
4 biological therapies
ipilimumab, pembrolizumab, vemurafenib, dabrafenib
Dacarbazine chemotherapy used to be the mainstay of treatment but
20% response rate, median duration of response 5-6 months before disease progression
No significant effect on overall survival
How does Ipilimumab work?
Ipilimumab is a recombinant human monoclonal antibody that binds to CTLA-4 (cytotoxic T-lymphocyte-associated antigen 4
(The CTLA-4 molecule serves as an “immune
checkpoint” that down-regulates pathways of T-
cell activation and prevents autoimmunity. By
blocking this function, ipilimumab potentiates
the antitumour T-cell response, resulting in
unrestrained T-cell proliferation.
Thus, the mechanism of action of ipilimumab’s
effect in patients with melanoma is indirect,
possibly through T-cell mediated antitumour
immune responses.
)
Ipilimummab s/e
diarrhoea rash pruritus fatigue nausea & vomiting decreased appetite abdominal pain colitis, hepatitis
vemurafenib mode of action
Oral tyrosine kinase inhibitor - BRAF inhibitor
BRAF is a gene – when it is mutated (in 60% of melanomas) it becomes constitutively active cell proliferation & tumour growth
Vermurafenib only suitablye for
patienst with BRAF V600 mutation
vemurafenib s/e
Fatigue
Joint pain (may need to take painkillers or use heat/ice packs)
Rash (may need emollient, antihistamine or painkillers)
Sensitivity to sun (SPF 30-50 needed in all weathers, wear long sleeves, apply a UV resistant film to windows)
Nausea
Alopecia
Pruritus
Headache
What might you give for the skin when treating with vermurafenib
emollient, antihistamine or painkillers for rash
ice pack/pain killers for joint pain
suncream needed in all weathers
pt should monitor what when treated with vemurafenib
Cutaneous squamous cell carcinomas have been reported in 20% of patients (these are minor skin cancers) so patients should be aware to check for any new/changing skin lesions. These can usually be easily treated by removing them surgically.
Severe skin reactions have been reported rarely and patient should be told to stop treatment immediately if they develop any blistering of the skin.
interactions con dabrafenib/vemurafenib
metabolised by cyp
s/e dabrafenib
Fever (patients should report temp >38) Fatigue Joint pain Rash Headache Nausea Diarrhoea
mode of action of dabrafenib
BRAF inhibitor
What does BRAF gene do?
BRAF is a gene – when it is mutated (in 60% of melanomas) it becomes constitutively active cell proliferation & tumour growth
2 important s/e for dabrafenib
Cutaneous squamous cell carcinomas have been reported in 10% of patients (these are minor skin cancers) so patients should be aware to check for any new/changing skin lesions. Remove surgically.
-Uveitis has been reported in 1% of patients – this can damage vision if it is not treated. Patients should report any eye redness/ irritation, blurred vision, eye pain, floating spots before the eyes.
pembrolizumab mode of action
immuno-oncology therapies called anti-PD-1s (programmed death receptor-1).
Humanized monoclonal antibody given by IV infusion that blocks the interaction between PD-1 (programmed death receptor-1) found on T cells and its ligands, PD-L1 and PD-L2.
By blocking the interaction with the receptor ligands, pembrolizumab releases the PD-1 pathway mediated inhibition of the immune response, including the anti-tumour immune response (i.e. it “takes the brakes off the immune system”).
perbrolizumab is made available under special circumstantes…
it isnt licensed but we are using it as part of the UK Early Access to Medicines scheme - unkown safety issues
s/e of pembrolizumab
Fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhoea
draw the pathway of treatment options
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