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personalised medicine and cancer > Cancer Part 2 > Flashcards

Cancer Part 2 Flashcards

1
Q

State the limit to the usefulness of cytotoxic chemotherapy

A

Access
Side effects
Resistance
End-point

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2
Q

Cytotoxic agents are alkylating agents. True/false?

A

True

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3
Q

state the physical barrier to the use of cytotoxic chemotherapy

A

Chaotic nature of tumour blood vessels and blood flow
Composition of tumour interstitium
Disturbed convection/diffusion into interstitial space of tumours:-
High tumour interstitial pressure (IP)
Tumour hyperthermia
Necrotic interstitium

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4
Q

IV cytotoxic agents can stimulate the vomiting reflex via systemic circulation. True/False

A

True

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5
Q

State how cytotoxic drugs can cause damage to the GIT

A

Mucositis/mouth ulcers:- painful inflammation of oral mucosa - leads to ulcers, fungal infection, speech/eating/swallowing difficulties.

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6
Q

Cytotoxic agents can damage the haemopoietic system. True/False

A

True

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7
Q

Describe how Cytoxic agents can lead to myelosuppression

A

Effects of tumour itself/RT
Difficult to recognise in neutropaenic patient - fever only
Opportunistic infections - fungal and viral

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8
Q

Treatment of Myleosupreesion(bone marrow damage)

A

Timing of doses/haemopoietic monitoring
Transfusions - blood granulocytes, platelets, autologous blood/marrow
CSF’s - accelerate bone marrow recovery

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9
Q

State how to prevent myelosuppression

A

Avoid exposure to infection
Patients do better at home
Avoid infected people/crowds
Watch kitchen hygiene

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10
Q

Facts about hair loss in cytotoxic chemotherapy

A

Loss of hair - often seen after 1-2 weeks, reversible
Scalp tourniquets or chilling of the scalp can be used
Patients can:-
Cut hair short
No strong chemicals
No aggressive brushing/towelling/hair drying
Wigs available but expensive for good ones

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11
Q

CT agents can sterilize patients during cancer therapy. True/false?

A

True

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12
Q

Renal toxicity with cis platin can be treated with ?

A

Mannitol diuresis

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13
Q

Haemorrhagic cystitis with ifosfamide and cyclophosphamide can be treated with?

A

Diuresis

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14
Q

State how to manage carCardiotoxicity with doxorubicin

A

careful ECG monitoring

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15
Q

many cytotoxic agents are mutagenic eg alkylating agents. True or false?

A

True

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16
Q

cytotoxic agents can lead to what disease?

A

treatment-induced neoplasia, often leukaemias

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17
Q

Treatment-induced neoplasia develops after how many years?

A

10-15years later

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18
Q

list the possible mechanisms of anti-cancer drug resistance

A

see slide 14

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19
Q

facts about drug resistance

A

Multidrug resistance (MDR)
Amplified gene product (MDR-1 gene)
Codes for transmembrane P-glycoprotein (P170)
ATP-dependent efflux pump, high levels in liver, pancreas, colon, lung, renal
Imparts intrinsic resistance to many chemotherapeutic agents
Inert pump blockers being sought

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20
Q

Facts about cancer treatment end point

A

Once at <10^9 cells tumour no longer palpable
Below <10^7 cells, no longer visible by x-ray

Patient might think that he/she is cured, bulk of tumour still present
Pretreatment with surgery/RT decreases tumour mass, fewer ‘rounds’ of CT, before resistance/toxicity forces therapy to stop

When do you stop treatment and leave the body to eliminate the residual cells?

21
Q

List the two groups of the cytotoxic agent

A

Cell cycle-specific
cell cycle non specific

22
Q

Describe cell cycle-specific drugs

A

Schedule dependent - can be given as infusion and allow cells to progress into drug sensitive phase

23
Q

Describe Cell cycle (phase) non-specific

A

Can give drugs at any phase of the cell cycle
Dose-dependent - Activity dependent on dose

24
Q

Facts about the administration of anti cancer agents

A

Combination chemotherapy
Co-therapy using drugs with minimal overlapping mechanisms of action and toxicities
Alternate myelosuppresive and non- myelosuppresive drugs
Continuous antineoplastic effect
Allows bone marrow recovery

25
Q

What are alkylating agents?

A

Cell cycle non-specific agents - but proliferating cells most sensitive (G1 and S)
Toxic to any rapidly dividing cells
Transcription affected and protein synthesis suppressed
Alkylating agents used in combination - solid and lymphatic tumours
Mutagenic and carcinogenic - secondary malignancy (acute leukaemia)

26
Q

What makes alkylating agents effective?

A

Effective by binding covalently to nucleophilic groups
N7 and O6 of guanine
N1 and N3 of adenine
N3 of cytosine

27
Q

What position is probably the most critical for cytotoxic action in alkylating agent

A

Guanine N7 position

28
Q

what is the mechanism of action of alkylating agent

A

Inter-strand cross-linking of DNA strands - stops strand separation
Intra-strand cross-linking
Base ring cleavage - strand cleavage
De-purination - strand cleavage
Tautomeric mutation - G pairs with T, GC to AT in daughter cells
Ineffective repair - frameshift mutation

29
Q

facts about Nitrogen Mustard

A

Bischloroethylamines - developed from sulphur/nitrogen cmpds used for chemical warfare during WWI (HCl is released into lungs of the victim)
Survivors developed lymphocytopaenia
Drug developed in the 1940s for Hodgkins leukaemia.

30
Q

Describe how alkylating agents work

A

Undergo intramolecular cyclisation forming an unstable ethylene immonium cation
Tertiary amine is transformed into quaternary ammonium cmpd
Ring opens out to form reactive carbonium ion which performs the alkylation
Carbonium ion is unstable reacts with an electron donor

31
Q

Most alkylating agents are bifunctional. True/false?

A

True

32
Q

List the side effects of Alkylating agents

A

Extravasation damage
N & V
Mucositis
Myelosuppression
Alopecia
Depressed gametogenesis
Increased risk of non-lymphocytic leukaemia
Drug handling/waste handling

33
Q

Facts about Nitrogen Mustard

A

Mechlorethamine - one of the most potent antineoplastic agents
Very unstable (T1/2 < 10 mins via iv)
Given as part of MOPP regime
Mechlorethamine
Oncovin
Prednisone
Procarbazine
Little drug excreted
Effective vs Hodgkins
Palliative use for bronchus, ovary, breast, and other solid tumours

34
Q

List the side effect of Mechlorethamine

A

All those already mentioned
Centrally mediated N & V and bone marrow effects can be severe and dose limiting
Extravasation is a problem – reactivity at injection site

35
Q

The most generally useful alkylating agent is called?

A

Cyclophosphamide & ifosfamide

36
Q

Cyclophosphamide is administered via what route?

A

Oral

37
Q

What is the route of administration of Ifosfamide?

A

IV

38
Q

both Cyclophosphamide and Ifosfamide are prodrugs activated by?

A

hepatic P450 - liver unharmed

39
Q

Resistance to alkylating drugs occurs from?

A

Increased DNA repair
Increased production of thiols (glutathione)

40
Q

state how alkylating drugs are used

A

oral admin, singly or in combo for a variety of neoplastic disease
Burkitt’s lymphoma and other lymphomas
ALL (acute lymphoblastic leukaemia)
Breast cancer
Several others
Can be given i.v., i.m. and by regional perfusion

41
Q

List toxicity associated with Alylating drugs

A

N/V/D
Alopecia
Myelosuppression
Haemorrhagic cystitis - fibrosis of bladder - due to acrolein
Amenoohoea/sterility
Secondary malignancies

42
Q

List the side effects that are less significant in Cyclophoshamide

A

N and V
Alopecia

43
Q

Chlorambucil is an alkylating agent indicated for ?

A

Oral admin for lymphocytic leukaemias – esp CLL

44
Q

State the role of a carrier in Chlorambucil

A

Carrier molecule delays activation of drug - better distribution

45
Q

State the name of an alkylating agent indicated for Myeloma and Ovarian?

A

Melphalan

46
Q

A carrier target for melanoma seen in Mephalan is known as

A

Phenylalanine

47
Q

List examples of other mustards?

A

Uramustine, oestramustine

48
Q

Are Nitrogen mustards able to cross the blood brain barrier?

A

No because they are too polar but Nitosoureas have been developed to address this

49
Q

an example of a Nitrourea is ?

A

Carmustine

personalised medicine and cancer (16 decks)

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