Cancer treatment intent

Question 1

Sytemic chemotherapy different aims

Answer 1

Metastatic disease
Adjuvant therapy - clean up micro cancer cells
Primary therapy - neoadjuvant - shrink tumour to allow surgery if inoperable
Chemoprevention

Question 2

Palleative chemo how toxic

Answer 2

Treatment should be well tolerated and adverse effects absolutely minimal - should not expense perfomrance status at all

Question 3

Ajuvant chemo what intent is

Answer 3

Erodicate micrometastatic disease
Greater toxicity accepted - chasing cure
Increased morbidity and mortality (up to 40%)

Question 4

What can neoadjuvant chemo acheive

Answer 4

Reduce requiremtn for surgery
Increase likelihood successful debulking
Reduce duration hospital and fitness after surgery

Question 5

When do patients need to starttreatment chemo

Answer 5

31 days after agreed treatment plan
62 dyas after 2 week wait referral

Question 6

What is one cycle of chemo

Answer 6

every 21 to 28 dyas
6 cycles normally

Question 7

Low dose therapy when start next cyce

Answer 7

When myeloupression recovered eg
neutrophils >1
Platelets >100

Question 8

Low dose therapy what effect on bone marrow

Answer 8

Few days of neutropenia at start then normally recover

Question 9

What can give to boost bone marrow recovery

Answer 9

IM GCSF - colony stimulating factor
once a day for 7 dyas

Question 10

How is neutropenia minimalised in high dose therapy

Answer 10

G-CSF to recover marrow
Autologous stem cells harvested and replaced

Question 11

What effect does using autologous stem cells have in marrow supression high dose chemo

Answer 11

16-21 days to revover from bone marrow supression rather than 6-7 weeks

Question 12

What is dose dense therapy

Answer 12

Fractionating intended dose of drug - administer each fraction more frequently
Used in breast and ovarian

Question 13

Toxicity of chemo vs anti cancer effect

Answer 13

peak plasma concentration determines toxicity therefore less toxic if dose dense chemo
Anti cancer effect if accumulative over time therefore still as effective

Question 14

Benefits of dose dense therapy

Answer 14

Overcome drug resistnace
Greater cell kill
Some patietns may show disease progression when getting chemo every 3 weeks and then start to regress on dense dose malignancy

Question 15

What is alternating threapy

Answer 15

Different drugs given on alternating schedule eg biweekly
Allows overalp of different drugs w toxicities

Question 16

Why is alternating therapy used

Answer 16

No overlapping toxxicity
Overcome drug resistance
Used in haematological cancer

Question 17

Why is when drug is cytotoxic in cell cycle imporant

Answer 17

Cells at G2M interface arrested (drugs eg vinca alkaloids) more susceptible to other treatments eg radiotherapy at that stage
If go to G0 - not susetible to chemotherapy

Question 18

WHy need new treatments

Answer 18

<10% cancers cured by chemo
Response by cell type and resistance mechanisms

Question 19

Potential routes to new therapies

Answer 19

Improve exisitng drugs eg giving pro drug orally rather than infusion
New targets
Targeted therapy
Impove identification of new compunds

Question 20

What determines orgnas susceptibility to metastatses

Answer 20

Blood supply
Expression of adhesion molecules on cell surface (eg kidney low expression therefore mets rare)

Question 21

What may tumour shrinkage actually represent

Answer 21

May be other cells around the tumour not acutal tumour cells

Question 22

Chemotherapy trial drug stages

Answer 22

15 years lab to market
Preclinical - 6.5 years
1.5 years phase 1 - maximum dose of drug tolerated
2 years phase 2 - response assessment at max dose
3.5 years phase 3 - compare to current treatment
1.5 years FDA approval

<1 % drugs leave lab
10-20% get approved

Question 23

What is common toxicity criteria

Answer 23

Severity of several hundred side effects from 0-4
Used to evaluate how toxic treatment is

Question 24

What criteria use to assess treatment response

Answer 24

RECIST - response evaluation criteria in solid tumours
Alos overall survival rates for drug

Question 25

What evaluate in chemo treatment

Answer 25

Overall surivval duration
Response to treatment
Remission rate
Disease free survival
Response duration
WOL
Treatment toxicity

Question 26

What is the role of imaging after cyle 3 of chemotherapy

Answer 26

If tumour is responding

Question 27

RECIST criteria

Answer 27

Complete response - disappearance of all target lesions
Partial response - at least 30% decrease in long diameter
Progressive - 20% increase in LD of target lesions, 5mm increase or appearance of one or more new lesions
Stbale disease - neither sufficient shrinkage for PR nor PD

Question 28

What rates can use to evaluate cancer

Answer 28

Remission rates
Overall surival rates

Question 29

What is complete vs parital remission

Answer 29

Complete - remains disease free for 5 years
Partial - some shrinkage but not all signs and symtpoms of cancer c=gone

Question 30

What is disease free survival

Answer 30

Length of tume after treatmnet for cancer where patient has no symptoms or signs of disease

Question 31

What is measurable disease

Answer 31

At least one lesion that can be accurately measured in at least one dimension eg longest diameter

Question 32

Criteria for measurable disease

Answer 32

Lesion must be >10mm CT and MRI assessment, clinical exam
Lesion >20mm on plain X ray

If >5mm slice thick, measurability = lesion w LD>2 x slice thickness

Malignant lymph nodes - short axis diameter >15mm to be considered pathological and measurable

Question 33

What is non measurbale disease in cacner

Answer 33

Ascites, peritoneal invasion, effusons, sometimes tumour marker levels

Question 34

What is residual disease

Answer 34

When cancer still present at end of chemotherapy
Sometimes difficult to differentiate between normal tissue etc
Adverse prognostic factors
May have more chemotherapy suitable

Question 35

Why can sequencing be improatnt

Answer 35

Some cancer MOA may make cell more vulnerable to the next drug but only in that order