Targeted Agents & Hormone therapy

Question 1

Name the types of targeted agents

Answer 1

Tyrosine Kinase inhibitors: Sunitinib (sutent), Erlotinib
Monoclonal antibodies: Trastuzumab/Herceptin, Rituximab, Ipilimumab
mTor inhibitors: Temsirolimus, Everolimus

Question 2

When is Herceptin used?

Answer 2

HER2 breast Ca

Adjuvant & metastatic treatment

Question 3

When is Ipilimumab used?

Answer 3

Metastatic melanoma

Blocks regulatory immune function achieving remission/response

Question 4

Why are drugs interactions important to consider with tyrosine kinase inhibitors?

Answer 4

Metabolised by the liver via CYP pathways

Question 5

When is Sunitinib used?

Answer 5

Anti-VEGFR (block cell growth factors & angiogenesis)

Palliative treatment of renal cell Ca, Pancreatic neuroendocrine, GI stromal

Question 6

When is Erlotinib used?

Answer 6

Anti-EGFR

Non-small cell lung cancer with EGFR mutation

Question 7

What does chronic dosing lead to?

Answer 7

• Chronic toxicity: Low grade symptoms (mild diarrhoea, taste disturbance)
• Emergent toxicity: SE only apparent after months of treatment (thyroid)
• Risk of drug interactions
• Mounting cost

Question 8

When is hormone treatment used?

Answer 8

All stages of cancer:

• Shrink primary tumour (neoadjuvant/primary)
• Prevent or delay the growth of micro metastases following surgery (adjuvant)
• Shrink established metastases and improve quality and duration of life (Palliative)

Question 9

How do hormone therapies work?

Answer 9

Part of the steroid family
Interact with cytoplasmic protein receptors to form functional DNA transcription factors, affecting the transcription of multiple genes

Question 10

What is the most direct hormone therapy?

Answer 10

Removal of the source of growth-promoting hormone
Bilateral oophorectomy in pre-menopausal women
Bilateral orchidectomy

Question 11

How is reversible medical castration achieved in men & women and how does this work?

Answer 11

Use of long-acting LHRH analogues (Goserelin, Leuprorelin)

Receptor down-regulation in the pituitary, block LH and FSH production and, in turn, gonadal hormone output.

Question 12

Why is medical castration not suitable in postmenopausal women?

Answer 12

Sex hormone production extra-gonadal: Fat & adrenal glands

Question 13

How do hormone inhibitors work? Give an example

Answer 13

Tamoxifen

Block the binding of hormones to their receptors in tumour cells

Question 14

What are the 2 types of anti-androgens?

Answer 14

Steroidal: Cyproterone Acetate
Inhibit the androgen receptor & in the hypothalamus they substitute for testosterone, so stimulate negative feedback inhibition= dec LHRH
Non-steroidal: Bicalutamide
Inhibit testosterone in both tumour cells and hypothalamus, so feedback inhibition is lost and serum testosterone levels rise.

Question 15

What is the maximum androgen blockade?

Answer 15

Combination of a non-steroidal anti-androgen with an LHRH analogue strategy used in prostate cancer

Question 16

Why is increasing hormones sometimes beneficial?

Answer 16

High conc glucocorticoids can induce apoptosis in some malignant lymphoid cells
Lymphoid leukaemias, lymphomas, myeloma and Hodgkin’s Disease.

Question 17

What are progestogens?

Answer 17

Synthetic analogues of progesterone
Given for cancers arising in progesterone sensitive tissues
Breast, endometrium
Direct inhibition of tumour growth via acting as an agonist of the progesterone receptor

Question 18

Why may progestogens be used in palliative medicine?

Answer 18

Stimulate the appetite