Chemotherapy Drugs

Question 1

Inherited cause of cancer?

Answer 1

Defective BRCA1/2 genes in breast cancer; deficiency in DNA repair enzymes

Question 2

Acquired cause of cancer?

Answer 2

Viruses, carcinogens (asbestos, smoking, radiation) alcohol, drugs, sun, geographical location

Question 3

Proto-oncogenes

Answer 3

Normal genes which can mutate to become oncogenes Potential to cause cancer

Question 4

Metastasis, location of secondary tumour

Answer 4

1. primary tumour 2. invades near by tissue 3. grows new blood vessels (angiogenesis) 4. secondary tumour

Question 5

Objectives of cancer therapy

Answer 5

• *1. curing patient** - eliminating all traces of cancer
• *2. prolonging life** - shrinking tumours
• *3. palliative therapy** - improving Qol, reducing pain

Question 6

Difficulties in treating cancer?

Answer 6

• asymptomatic, until late symptoms
• detection methods are not 100% reliable
• hard to find primary site
• cancer cell similar to normal cells
• difficulties to exploit biochemical differences

Question 7

Aims of chemo

Answer 7

to kill all malignant cells in body

Question 8

Toxic effects of chemotherapy

Answer 8

• bone marrow suppression
• impaired wound healing
• loss of hair -damage to GI epithelium
• growth stunted
• reproductive system > sterility
• teratogenicity -bleeding and bruising
• N+V -kidney damage

Question 9

Classes of anti cancer drugs

Answer 9

• *1. cytotoxic** (alkylating, antimetabolites, antibiotics , plant derivatives ) = block DNA synthesis/ prevent cell division 2.hormones (+ their antagonist) = supress opposing hormone secretion or inhibit their actions
• *3.monoclonal antibodies** = target specific cancer cells 4.protein kinase inhibitors = block cell signally pathways in rapidly dividing cells

Question 10

What are the different classes of alkylating agents? (cytotoxic drugs)

Answer 10

• *Nitrogen mustards** -cyclophopshamide
• *Nitrosoureas -**lomustine CCNU, carmustine BCNU Platinum compounds -cisplatin, carboplatin
• *Busulphan**

Question 11

Have cytotoxic effects in rapidly growing cells - very reactive given IV
Mechlorethamine **
Cyclophosphamine
Melphalan
Chlormbucal
Bendamustine
Estraustine

Answer 11

examples of nitrogen mustards

Question 12

Nitrogen mustards : Cyclophosphamide

Answer 12

Prodrug - can be administered orally
Activated in the liver to phosphoramide mustard + acrolein Acrolein = haemorrhagic cystitis
Can cause cystitis

Question 13

What are the different classes of antimetabolites? (cytotoxic drugs)

Answer 13

• *Folate antagonists** - methotrexate
• *Pyrimidine analogues** - fluorouracil
• *Purine analogues** - fludarabine

Question 14

What are examples of cytotoxic antibiotics? (cytotoxic drugs)

Answer 14

doxorubicin
bleomycin

Question 15

What are example of plant derivatives? (cytotoxic drugs)

Answer 15

vincristine
vinblastine
vindesine

Question 16

• *Glucocorticoids** - prednisolone, dexamethasone Oestrogens - diethlstilbestrol
• *Progestogens** - megesterol
• *Gonadotropin-releasing hormone analogues** - goserelin Antioestrogens - tamoxifen
• *Antiandrogens** - flutamide

Answer 16

Different classes of hormones

Question 17

How do cytotoxic drugs work?

Answer 17

Block DNA synthesis/ prevent cell division

Question 18

How do hormones (and their antagonists) work?

Answer 18

They supress opposing hormone secretion or inhibit their actions

Question 19

How do monoclonal antibodies work?

Answer 19

Target specific cancer cells

Question 20

How do protein kinase inhibitors work?

Answer 20

block signalling pathways in rapidly dividing cells

Question 21

How do alkylating agents work?

Answer 21

target cells in DNA synthesis phase (S phase)
form covalent bonds with DNA to prevent uncoiling
SIDE EFFECTS
sterility increased risk of non-lymphatic leukaemia

Question 22

• Highly lipophilic* - cross the BBB to treat CNS tumours. Carmustine IV - multiple myeloma, non-Hodgkin’s lymphoma and brain tumours
• *Lomustine oral** - Hodgkin’s disease, malignant melanoma and certain solid tumours

Answer 22

example of Nitrosoureas

Question 23

What are platinum compounds (alkylating agents)

Answer 23

eg Cisplatin Potent alkylator -
binds to RNA > DNA > protein
Binds to purine bases (G,A,U)
Resistance may develop - DNA repair by DNA polymerase SIDE EFFECTS
very nephrotoxic (requires hydration), severe N+V, risk of tinnitus, peripheral neuropathy, hyperuriceamia (gout), and anaphylaxis

Question 24

Other platinum compounds

Answer 24

Carboplatin
derivative of cisplatin (ovarian and lung cancer)
Less side effects
Oxaliplatin
used to treat colorectal cancer (with fluorouracil and folinic acid)
Side effects bone marrow suppression (myelotoxic)

Question 25

What other alkylating agents are there?

Answer 25

• *Busulfan** - selective for bone marrow, leukaemia treatment
• *Procarbazine** - Hodgkins disease but cause hypersensitivity rash and inhibits MAOIs
• *Trabecteolin** - soft tissue sarcoma/advanced ovarian cancer but is hepatotoxic

Question 26

What are Folate antagonists (antimetabolites, cytotoxic drugs)

Answer 26

• essential for DNA synthesis/cell division
• *e.g Methotrexate**
• inhibits dihydrofolate reductase
• given orally, i.m , i.v or intrathecally
• low lipid soluility

Question 27

Explain Pyriminidine Analogues (antimetablites, cytotoxic drugs)

Answer 27

Complete with C and T bases which make up DNA and RNA

• *Flurouracil** (soild tumours, GI camcers and breast)
• *Capecitaine** (colon/colorectal cancer, breast cancer)
• *Cytarabine** (acute myeloblastic leukaemia)
• *Gemcitabine** (pancreatic/bladder/ovarian/breast)

Question 28

Explain _Purine analogues (_antimetablites, cytotoxic drugs)

Answer 28

Complete with A and C - inhibit purine metabolism
Mercaptopurine
Tiogunanine
Pentostatin
Fludaraine