Cancer treatment intent Flashcards
Sytemic chemotherapy different aims
Metastatic disease
Adjuvant therapy - clean up micro cancer cells
Primary therapy - neoadjuvant - shrink tumour to allow surgery if inoperable
Chemoprevention
Palleative chemo how toxic
Treatment should be well tolerated and adverse effects absolutely minimal - should not expense perfomrance status at all
Ajuvant chemo what intent is
Erodicate micrometastatic disease
Greater toxicity accepted - chasing cure
Increased morbidity and mortality (up to 40%)
What can neoadjuvant chemo acheive
Reduce requiremtn for surgery
Increase likelihood successful debulking
Reduce duration hospital and fitness after surgery
When do patients need to starttreatment chemo
31 days after agreed treatment plan
62 dyas after 2 week wait referral
What is one cycle of chemo
every 21 to 28 dyas
6 cycles normally
Low dose therapy when start next cyce
When myeloupression recovered eg
neutrophils >1
Platelets >100
Low dose therapy what effect on bone marrow
Few days of neutropenia at start then normally recover
What can give to boost bone marrow recovery
IM GCSF - colony stimulating factor
once a day for 7 dyas
How is neutropenia minimalised in high dose therapy
G-CSF to recover marrow
Autologous stem cells harvested and replaced
What effect does using autologous stem cells have in marrow supression high dose chemo
16-21 days to revover from bone marrow supression rather than 6-7 weeks
What is dose dense therapy
Fractionating intended dose of drug - administer each fraction more frequently
Used in breast and ovarian
Toxicity of chemo vs anti cancer effect
peak plasma concentration determines toxicity therefore less toxic if dose dense chemo
Anti cancer effect if accumulative over time therefore still as effective
Benefits of dose dense therapy
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
What is alternating threapy
Different drugs given on alternating schedule eg biweekly
Allows overalp of different drugs w toxicities
Why is alternating therapy used
No overlapping toxxicity
Overcome drug resistance
Used in haematological cancer
Why is when drug is cytotoxic in cell cycle imporant
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
WHy need new treatments
<10% cancers cured by chemo
Response by cell type and resistance mechanisms
Potential routes to new therapies
Improve exisitng drugs eg giving pro drug orally rather than infusion
New targets
Targeted therapy
Impove identification of new compunds
What determines orgnas susceptibility to metastatses
Blood supply
Expression of adhesion molecules on cell surface (eg kidney low expression therefore mets rare)
What may tumour shrinkage actually represent
May be other cells around the tumour not acutal tumour cells
Chemotherapy trial drug stages
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
What is common toxicity criteria
Severity of several hundred side effects from 0-4
Used to evaluate how toxic treatment is
What criteria use to assess treatment response
RECIST - response evaluation criteria in solid tumours
Alos overall survival rates for drug
What evaluate in chemo treatment
Overall surivval duration
Response to treatment
Remission rate
Disease free survival
Response duration
WOL
Treatment toxicity
What is the role of imaging after cyle 3 of chemotherapy
If tumour is responding
RECIST criteria
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
What rates can use to evaluate cancer
Remission rates
Overall surival rates
What is complete vs parital remission
Complete - remains disease free for 5 years
Partial - some shrinkage but not all signs and symtpoms of cancer c=gone
What is disease free survival
Length of tume after treatmnet for cancer where patient has no symptoms or signs of disease
What is measurable disease
At least one lesion that can be accurately measured in at least one dimension eg longest diameter
Criteria for measurable disease
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
What is non measurbale disease in cacner
Ascites, peritoneal invasion, effusons, sometimes tumour marker levels
What is residual disease
When cancer still present at end of chemotherapy
Sometimes difficult to differentiate between normal tissue etc
Adverse prognostic factors
May have more chemotherapy suitable
Why can sequencing be improatnt
Some cancer MOA may make cell more vulnerable to the next drug but only in that order
