Cancer Chemotherapy Flashcards

1
Q

Causes of cancer

A

Environmental exposure
Viruses
Oncogenes
Tumour suppressor genes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Cancer is

What is a tumour

Benign behaviour
Malignant behaviour

What do tumours arise from

A

Second leading cause of mortality
Continuous uncontrolled growth of cells
Any abnormal proliferation of cells

Stay confined to original location
Capable of invading surrounding tissue or invading whole body

Any type of cell in body and classified by that

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Treatments

When is radiotherapy possible

When is chemo required and what is it combined with

A

Surgery

Radiotherapy - when tumour is localised at diagnosis

Chemotherapy - once cancer metastasises so is required for effective cancer management

Combined with radiotherapy to allow resection to take place

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Surgery and radio therapy are usually more possible when

A

tumour remains localised at the time of diagnosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Chemotherapy drugs

Vary based on

A

More than 100 used today

  • chemical composition
  • route of administration - type of cancer targeted
  • side effects
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Types of chemo

A

Primary induction chemo

Neoadjuvant chemo

Adjuvant chemo

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Primary induction chemo

Effectiveness?

A

Administered in patients with advanced cancer for which no alternative treatment exists.
Can be curative in only a small subset of patients who present with advance disease. (i.e. Hodgkin’s and non-Hodgkin’s lymphoma in adults or lymphoblastic leukemia in children).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Neoadjuvant chemo

A

in patients with localised cancer for which alternative local therapies, e.g. surgery, exist but which are less than completely effective.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Adjuvant chemo

alternative to?

Effective in?

A

An adjuvant to local therapy such as surgery or radiation. Is effective in prolonging both disease-free and overall survival in patients with different type of cancer (i.e. patients with breast, colon gastric or non-small lung cancer)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Main goal of antineoplastic agents

A

Eliminate cancer cells without affecting normal tissues

All cytotoxic drugs affect normal tissues as well as malignancies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Therapeutic dose

Formula

A

A therapeutic index is the lethal dose of a drug for 50% of the population (LD50) divided by the minimum effective dose for 50% of the population (ED50).

LD50/ED50

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Log-kill hypothesis

A
  • Chemotherapeutic agents kill a constant PROPORTION of tumour cell population (first order kinetics), rather than a constant NUMBER of cells, after each dose
  • Solid cancer tumours – generally have a low growth fractions thus respond poorly to chemotherapy and in most cases need to be removed by surgery
  • Disseminated cancers- generally have a high growth fraction and generally respond well to chemotherapy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Drugs can be

CCNS can

A

Cell cycle specific (exert actions on cells traversing cell cycle) and cell cycle non specific

sterilize tumour cells whether they are cycling or resting in the G0 compartments.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

CCNS are

A

Alkylating agents/Antitumour antibiotics/Camptothecins/Platinuum analogues/Anthracyclines
Carcinogenic in nature and can increase the risk of secondary malignancies
Due to systemic effect
Can sterilise tumour cells whether they are cycling or in resting phase
Reduces cell proliferation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Alkylating agents - used to

A
  • treat a wide variety of haematologic and solid tumour (i.e. ovarian cancer, brain tumours)
  • immunosuppressant action
    • Most of the adverse effects are generally dose-related and occur
    primarily in rapidly growing tissues
    • Bonemarrowdepression
    • Nausea and Vomiting. Antiemetics are often given prior and after alkylating agents dosing
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Alkylating agents examples

A

Busulfan (Alkyl sulfuantes)

  • Mainly used for chronic myelogenous leukemia and other leukemias, lymphomas and myeloproliferative disorders.
  • Controls tumour burden but can not prevents transformation or correct cytogenic abnormalities.

Lomustine (Nitrosoures)

  • Requires biotransformation to agents that have alkylating or carbamoylating activities.
  • Can cross the blood brain barrier, mainly used to treat brain tumours.

Decarbazine (Triazenes)
- Used in the treatment of various cancers, among them malignant melanoma, Hodgkin lymphoma, sarcoma, and islet cell carcinoma of the pancreas. Mainly given IV, is bioactivated in the liver.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Issues with CCNS - resistance

Mechanism (3 methods)

A
  • Increased activity of DNA repair enzyme
  • Increase metabolic activation of the rug
  • Decrease influx of the drug
18
Q

Platinum analogues (are a type of?) e.g (most common)

Cisplatin mechanism

A

CCNS
Cisplatin
Mechanism unclear
Exert cytotoxic effect similar to alkylating agents

Form highly reactive platinum complexes
Intra strand and inter strand cross linkages
DNA damage
Reduce cell proliferation

19
Q

Cisplatin features

Used for? But poor at?

cleared by?

Adverse effects?

A

Highly bound to plasma proteins
Highly conc in kidney, intestines and testes
Used for these cancers
Poorly penetrates blood brain barrier
Cleared by kidney and slowly excreted in urine
Vomiting, nephrotoxicity, peripheral neuropathy and ototoxicity

20
Q

Taxanes

Type of

Mechanism - when does it occur

Example - used when, where is it metabolised, dose reduction when? Adverse effects

A

CCS

Alkaloid ester
Enhance tubulin polymerisation (occurs in absence of appropriate proteins)
Inhibition of mitosis and cell division

Paclitaxel

  • broad range of solid tumours
  • in liver 80% excreted in faeces - liver disease
  • nausea, emesis, hypersensitivity, myelosuppression, hypotension
21
Q

Anti tumour antibiotics
Type of?

Mechanism

Examples

A
CCNS
Bind to DNA through intercalation between specific bases 
- block synthesis of RNA, DNA or both 
- scission of DNA strand 
- interfere with cell replication 
1. doxorubicin 
2. mitomycin 
3. bleomycin
22
Q

Doxorubicin is a type of…

Used against?

Used with?

How?

A

Anthracycline
- Mainly used against breast, ovary, testicles, stomach, thyroid and bladder cancer. - Often used in combination with other anticancer drugs. - Generates free radicals leading to cardiotoxicity.

23
Q

Mitomycin
Type

Used in?

Mechanism

Used in combination with?

A

CCS
Highly toxic
- used in resistant cancers of stomach, colon and rectum.
- Its metabolite act like alkylating agent that cross-links DNA.
- It is active in all phases of the cell cycle.
- It is the best available drug to use in combination with radiotherapy to attack hypoxic tumour cells

24
Q

Bleomycin

Type

Features
Mechanism

Used for?

Administration?
Excretion?

Adverse effects

A

CCS

  • small peptide
  • binds to DNA resulting in single- and double-strand breaks, leading to inhibition of DNA biosynthesis
  • Causes accumulation of cells in G2 phase.
  • Used for lymphomas, head and neck cancer.
  • can be given SC, IM or IV.
  • Eliminated via renal excretion.
  • Pneumonitis, hyperpigmentation and spares bone marrow.
25
Q

Hormones and antagonists

3 types

A

Glucocorticoids
Oestrogen
Oestrogen antagonists

26
Q

Bisphosphonates

When does MS occur

A

Common in patients with advanced solid tumours and metastasis to skeleton

Myeloma, MS breast, prostate and thyroid

27
Q

Spread of cancer to bone is associated with

A
  • pain,hypercalcemia,anemia
  • increased risk of infection,
  • compression of the spinal cord and/or nerve roots
  • decreased mobility and skeletal fracture (catastrophic)
28
Q

Role of bisphosphonates

What happens after admin

Disadvantages

A
  • Slow down the rate of growth of bone crystal and their resolution by inhibiting osteoclasts and promote apoptosis
  • Reduce morbidity from bone metastasis by reducing skeletal events.
  • Lower calcium levels

25-40% excreted by kidney and rest taken up

Poor oral bioavailability
Gastrointestinal toxicities such as nausea, vomiting, indigestion, oesophagitis and diarrhoea

29
Q

Drug resistance is

What is ACQUIRED resistance

Specific to?

Multidrug resistance results in

Other mechanisms of resistance

A
  • Critical in chemo because some tumours can exhibit PRIMARY resistance
  • develops in response to exposure to a GIVEN anticancer agent

A single drug, due to single change in genetic machinery of a given tumour cell

Enhanced drug efflux and reduced intracellular accumulation of broad range of unrelated cancer agents

Drug not activated, Drug not metabolised to active form, drug target increased, alternative pathway activated instead

30
Q

To achieve a chemotherapeutic cure…

A

TOTAL CELL KILL
Early diagnosis and early institution of tx
Combination chemotherapy
Intermittent regimens
Adjuvant and neoadjuvant chemotherapy occasionally

31
Q

CCS categories

A

Antimetabolites/Taxanes/Vinca Alkaloids/Antimicrotubule inhibitor/Antitumous antibiotics

32
Q

Alkylating agents CCNS - mechanism

A

Highly reactive carbonium ion
Transfers alkyl group to nucleophilic sites on DNA bases
Affects cell proliferation

33
Q

Antimetabolites

Are a type of

What do they act on? Mechanism
3 types?

A

CCS

Intermediary metabolism of proliferating cells
Interfere with DNA and RNA growth by substituting normal building blocks of RNA and DNA during S phase

Folates antagonist
Purine antagonists
Pyrimidine antagonist

34
Q

Methotrexate

Is an

Negatives

Where does it act?

Adverse effects

A

Antimetabolite

Binds to active catalytic site of dihydrofolate reductase
inhibits synthesis of tetrahydrofolate
interferes with formation of DNA, RNA and key cellular proteins

Poor brain penetration, remains in tissue longer than folate prolonging inhibitor effect, remains unchanged in urine.

Cytotoxic, mainly on bone marrow
Immunosuppressive, preventing clonal expansion of B&T lymphocytes
Anti-inflammatory

Megaloblastic anaemia
Leukopenia
Alopecia
Nephropathy

35
Q

Purine antagonist e.g

Used for
In order to work?

Mechanism

Negatives

Adverse effects

A

6 mercaptopurine

Childhood acute leukaemia
Must be metabolised into active form
Inhibits synthesis of purine nucleotides
Metabolites alter synthesis and function of RNA and DNA

Does not cross BBB

Nausea, vomiting, fatigue stomach/abdo pain, fever

36
Q

pyramidine antagonist e.g

Acts on?

What required?

Half life?

Adverse effects

A

5 fluorouracil
Stomach, colon, breast, ovaries, liver and skin cancer

Activation via enzymatic reaction
Extreme short half life (5-10 mins)
Nausea, vomiting, headache, mood disorder, cardiotoxicity, GI ulceration and bleeding, vein pigmentation, local pain, burning, dermatitis

37
Q

Vinca alkaloids

A

CCS

Natural alkaloid products derived from Vinca Rosea

Inhibit tubular proliferation
Disrupt assemble of microtubules
Mitotic arrest in metaphase
Cell division ceases –> cell death

38
Q

Vinca alkaloids e.gs and uses (2)

A

Vincristine
childhood cancers, H&NH lymphoma, lymphosarcoma
= neurotoxicity

Vinblastine
Hodgkin’s disease and other lymphoma
Bone marrow suppression, nausea, vomiting and alopecia

39
Q

Glucocorticoids

Used in? Due to?

A

Used in acute leukaemia and lymphomas

Lymphocytic effect

40
Q

Oestrogens

Used as?

A

Antagonists of androgen so antagonise effect of androgens in androgen dependent prostate cancer

41
Q

Oestrogen antagonists

Used in?

Adverse effects

A

Breast cancer
Oestrogen receptor DOWN regulator

Hot flushes, emesis, menstrual irregularities