Principles of Cancer Treatment (Part 2) Flashcards
1
Q
What is the combination chemotherapy and its uses?
A
- Using more than one agent to overcome the following problems:
1. Sensitivity: tumours may be non-responsive at clinically achievable doses.
2. Toxicity: avoid the use of high doses
3. Resistance: inherent genetic stability commonly leads to non-random mutation and confers resistance.
2
Q
Desirable characteristics for combination therapy:
A
- Agents must be effective (>20% response rate when used alone)
- Agents should have different dose-limiting toxicities
- Agents should not antagonise each other when combined.
- Agents should be given in a dose equivalent to when the drug is given alone
- Agents should have different pharmacological action
- Increase the overall intensity of therapy directed at cancer.
3
Q
Drug-related factors
A
Pharmacokinetics: ADME
Drug distribution to site of tumour microenvironment
MOA: cell-cycle specificity
Combination chemotherapy
4
Q
Tumour-related factors
A
- Tumour growth kinetics
- Tumour size
- Site of tumour and tumour vascularization
- Tumour cell heterogeneity - resistance
5
Q
Tumour growth kinetics
A
- treatment is most successful with in tumours with small tumour burden and high growth fraction
» early detection/screening programs are important
6
Q
Tumour size
A
- in large tumours the cells are least likely to be proliferating and hence unlikely to be killed by chemotherapy agents.
- the larger the tumour,
» the greater probability of metastasis
» the greater the probability of drug-resistant cells
» poor drug distribution
7
Q
Tumour cell Heterogeneity - resistance
A
Heterogeneity:
- genetically unstable –> reproduce inconsistently, clones have different characteristics
- moving target for drug therapy –> tumour cells resistance
8
Q
Site of tumour and tumour vascularization
A
- Sanctuary sites (CNS, testis)
» drug penetration poor, difficult to get a sufficient concentration of chemotherapy agent to destroy cancer cells. - Poor blood supply
» large tumor will have central necrosis (chemotherapeutic agents not effective there)
9
Q
Patient-related factors
A
- Patient’s overall health status
- Immuno-competency
- Organ functions
- Treatment history
- Patient’s age
10
Q
Patient’s overall health status
A
- ECOG/Karnofsky Performance Status Criteria: subjective measure to guide treatment decisions
- Chemotherapy doses attenuated only in presence of life-threatening toxicities to maintain full anti-tumour activity.
- Goldie-Coldman hypothesis: mutations that favour drug-resistance may be developed over time, resulting in the selection of chemotherapy-resistant cancer clones.
- Mechanisms of tumour cell resistance to antineoplastic drugs include:
» decreased drug accumulation (drug uptake + efflux)
» altered drug metabolism
» increased repair to drug-induced damage
» alteration of drug target
11
Q
Immuno-competency
A
- impaired cell-mediated immunity is a poor prognostic factor.
- disease progression, anti-cancer therapies and immunosuppressants can weaken the host’s immune system.
12
Q
organ functions
A
- check for renal and hepatic impairment before and during treatment
- dose reduction is often empirical
13
Q
treatment history
A
- previous therapies can effect organ toxicity
- myelosuppression is major dose-limiting toxicity
- if toxicity is encountered, reduce dose and lengthen dosing interval.
14
Q
patient age
A
- myelosuppression recovers more slowly amongst aged patients
- aged patients may also have concomitant diseases that need to be factored in as well.
15
Q
Differences in curative vs palliative treatment
A
Curative:
- reduction in dose intensity is accepted only under compelling reasons (why: main purpose is to cure patient).
- long-term toxicities are undesirable, but intense short-term toxicities that are reversible are acceptable if there is no better alternative.
Palliative:
- intense short term toxicities are not acceptable (why: main purpose is symptom relief)
- long-term toxicities are not even a consideration.
