Three basic principles of CA treatment?
#1 Establish the diagnosis - biopsy (cytology, excisional, incisional), no other test short of a biopsy that can establish the diagnosis although there dx may be suspected prior to the definitive biopsy. The pathological report may also include info that is predictive of a response or non-response to a particular chemotherapy drug
2. determine the stage --> determines prognosis & treatment using the uniform system set by physcians; commonly used staging tests are physical exam, blood tests and imaging modalities such as x-rays and CT scans
3. determine the prognosis and treatment -
in general: cancer confined to the organ of origin (usually treated with surgery/radiation therapy) > cancer confied to the organ of origin with spread to the regional draining lymph nodes > metastatic dz (w/mets or high chance of mets require systemic, blood-borne therapy)
4. educate the patient about the prognosis and treatment
5. Clearly define the goals of any therapy (curative/palliative), and clearly define the expectation of the benefit for the patient and indicate hwo the patient will monitored and disease response assessed. Have a plan for monitoring response
6. Evaluate the pt to make certain that the patient can tolerate the potential side effects of any treatment
What is the prognosis as a function of stage?
localized disease > local-regional disease > disseminted disease
What is the purpose of chemotherapy?
Who are the pt that it is given to? (3)
Chemotherapy is a systemic therapy - drugs given orally or parenterally in an attempt to control or eradicate a malignant process
It is given to pt who:
-Have had cancer removed but who are believed to be AT RISK of having micrometastatic disease (adjuvant chemotherapy)
- with curative or palliative intent who have clinically apparent metastatic (adv, mets) dz
- to achieve cytoreduction prior to surgery (neoadjuvant chemo)
What is the TNM grading?
T - local vs spread
1 - just to the submucosa, 2- into the muscularis propria 3- invales thorugh the muscularis propria, 4- penetrates to the surface of the visceral peritoneum or invades other adjacent structures
N - lymph node
1- 1-3 regional nodes involved 2- > 4 regional lympnodes invovled
M - metastasis
0- none 1- yes
How is tolerance to chemotherapy assessed? (3)
1. Patient performance (0-5)
2. End organ function
3. Requires knowledge of efficacy of treatments, drugs to be used, known side effects and pharmacology
How is patient performance status assessed (5)?
0= fully active
1= restricted in physically strenous activity but ambulatory and able to carry out work of a light or sedentary nature; light house work, office work
2= ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours
3 = capable of only limited selfcare, confied to bed or chair more than 50% of waking hours
4 = completely disabled. Cannot carry any selfcare; totally confied to bed or chair
5 = death
What order does the killing of cancer cells by chemotherapy follow? what does this signify?
= the same fraction of CA cells is killed with each administration of chemotherapy; thus, in order to achieve a cure with chemotherapy, multiple courses of chemo will have to be given
ie two long cell kill means that 10^2 cells will die w/each administration of the drug; note though that tumor regrowth in-between cycles of chemotherapy may occur
Single agent vs combo chemo?
Combo therapy was able to produce significant remission or cures as compared to single drug use.
Drug combos are effective b/c:
- provide maximal cell kill within the range of toxicity tolerated by the host for each drug (fractional cell kill / log cell kill is increased in combo compared to single agents)
- com drugs with different MOAs provide a broader range of coverage of de novo resistant cell lines.
What are the 5 rules to create a chemo combo therapy?
1. drugs chosen should possess activity against the disease when utilized as a single agent (determined by phase II studies)
2. Drugs chosen should have NON-OVERLAPPING TOXICITIES (except for hair loss, myelosuppression, n/v)
3. combine drugs with different MOAs
4. combine cell cyle specific and cell cycle non-specific drugs
5. drugs should be given in an optima dose and an optimal schedule - a dose response relationship exits between response rate and dose of chemotherapy administered
When is adjuvant therapy after surgery indicated? (8)
dont' have to commit to memory but have an idea
1. node positive and selected node negative breast CA
2. stomach CA
3. pancreas CA
4. selected pt with melanoma
5. node positive colon and rectal CA
6. osteogenic sarcoma
7. lung CA
8. testicular CA
How is it possible that a patient can have a cancer removed as in the stage 1 and stage 2 breast and lung cancers presented in the above table, and develop metastatic disease at a later time?
Indicate how the Goldie-Coldman hypothesis supports the administration of chemotherapy to patients who have had a cancer removed but are at risk of recurrence at a later date.
What are the 4 steps of chemotherapy for metastatic dz:
1. choose a particular regimen that has been shown to improve overall survival
2. pt has measurable or evaluable disease on imaging
3. certain number of cycles is given and then the patient is reimaged
- stable dz, partial remission or complete remission? CONTINUE therapy for a certain # of cycles; pt needs to be able to tolerage
- if progression of dz - chemoresistance is present and the regime is changed if appropriate
4. at some point, the pt's cancer becomes resistant to all the drugs and the pt gets progressively weaker and palliative, hospice care is appropriate
What are the 3 main drugs for testicular CA?
What tests should you conduct before administrating this therapy?
Bleomycin, days 1, 8, 15
Etoposide IV days 1-5
Cisplatin IV days I-5
What test do you want to order before?
Bleo - lung function
Etoposide - kidney and liver tests
Cisplatin - kidney fxn test
What are some chemocurable cancers? (6)
diffuse large B-cell lymphoma
metastatic testicular CA
What are some chemo-treatable (not curable CA)
Metastatic cancer of:
breast, colon, prostate, pancreatic, melanoma, lung