VP L5 Malignant melanoma

Question 1

3 main types of skin cancer

Answer 1

malignant melanoma

non-melanoma cancers (basal cell carcinoma/squamous cell carcinoma)

Question 2

Risk factors for MM (4)

Answer 2

sun exposure - intense intermittent exposure
number of moles
fair skin
family history

Question 3

pt usually presents with

Answer 3

changing/enlarging/irritating lesion

Question 4

What is the process of examination

Answer 4

dermascope,
excisional biopsy
histopathology
physical examination - lyphadectomy, hepatomegaly or other suspect lesions (looking for mets)

Question 5

Who is suitable for surgery

Answer 5

stage 0-3 (over 50% of stage 3 tumours reoccur)

Question 6

stage four tumours treated by ~(2)

Answer 6

chemo

biological therapies

Question 7

4 biological therapies

Answer 7

ipilimumab, pembrolizumab, vemurafenib, dabrafenib

Question 8

Dacarbazine chemotherapy used to be the mainstay of treatment but

Answer 8

20% response rate, median duration of response 5-6 months before disease progression
No significant effect on overall survival

Question 9

How does Ipilimumab work?

Answer 9

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.
)

Question 10

Ipilimummab s/e

Answer 10

diarrhoea 
rash
pruritus
fatigue
nausea & vomiting
decreased appetite
abdominal pain
colitis, hepatitis

Question 11

vemurafenib mode of action

Answer 11

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

Question 12

Vermurafenib only suitablye for

Answer 12

patienst with BRAF V600 mutation

Question 13

vemurafenib s/e

Answer 13

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

Question 14

What might you give for the skin when treating with vermurafenib

Answer 14

emollient, antihistamine or painkillers for rash
ice pack/pain killers for joint pain

suncream needed in all weathers

Question 15

pt should monitor what when treated with vemurafenib

Answer 15

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.

Question 16

interactions con dabrafenib/vemurafenib

Answer 16

metabolised by cyp

Question 17

s/e dabrafenib

Answer 17

Fever (patients should report temp >38)
Fatigue
Joint pain
Rash
Headache
Nausea
Diarrhoea

Question 18

mode of action of dabrafenib

Answer 18

BRAF inhibitor

Question 19

What does BRAF gene do?

Answer 19

BRAF is a gene – when it is mutated (in 60% of melanomas) it becomes constitutively active  cell proliferation & tumour growth

Question 20

2 important s/e for dabrafenib

Answer 20

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.

Question 21

pembrolizumab mode of action

Answer 21

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”).

Question 22

perbrolizumab is made available under special circumstantes…

Answer 22

it isnt licensed but we are using it as part of the UK Early Access to Medicines scheme - unkown safety issues

Question 23

s/e of pembrolizumab

Answer 23

Fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhoea

Question 24

draw the pathway of treatment options

Answer 24

!