Ap-Cancer Drugs

Front 1

CANCER

What is the subclinical or latent phase of the cancer?

Back 1

The time from the inception of a cancer (transformation of a single cell) to the time that the tumro becomes clinically detectable (one billion cells)

During this period it is impossible to detect

Front 2

CANCER

What is tumor cell heterogeneity?

Back 2

Tumor cells are very different from one another even though cancer cells look similar under the microscope.

Front 3

CANCER

What is the tumor growth fraction?

Back 3

The dividing cells / total cell number

Front 4

CANCER

What are the four steps in the metastatic process?

Back 4

1. clonal evolution
2. intravasation
3. extravasation
4. growth in the distant metastatic sites.

Most often occurs in the subclinical or latent phase of the cancer

Front 5

CANCER

What does the stage of the cancer tell us?

Back 5

Stage of cancer indicates the extent of disease at the time of diagnosis and determines the prognosis and treatment.

Front 6

CANCER

All staging systems are reduced to three basic stages:

Back 6

1. CA localized to organ of origin
2. CA localized to organ of origin with spread to regional draining lymph nodes
3. disseminated disease

Front 7

CANCER

How does resisitance to CA occur?

Back 7

It occurs as a chance, spontaneous event.

Front 8

CANCER

Can we currently target the antineoplastic drug to the CA cell?

Back 8

NO!!!

Front 9

CANCER

What is the Skipper Hypothesis?

Back 9

The ability of chemotherapy to cure CA is inversely proportional to the tumor burden.

Front 10

CANCER

What are five examples of chemocurable CA's (that never develop resistance to chemotherapy);

Back 10

1. disseminated testicular CA
2. some lymphomas
3. some leukemia's
4. Hodgkin's disease

Front 11

CANCER

Five toxicities due to effect of chemotherapy on normal dividing cells?

Back 11

1. transient myelosuppression
2. temporary hair loss
3. transient GI toxicity (damage to nL dividng cells of oral and GI mucosa)
4. sterility (effect of drug on dividing germ cell epithelium
5. second neoplasms due to the mutagenic effect of the drug on normal cells.

Front 12

CANCER

When does hair loss occur?

Back 12

2-3 wks after the first administration of the drug

Front 13

CANCER

When does myelosuppression occur?

Back 13

7-14 days following drug adminstration

Front 14

CANCER

When do sore mouth and diarrhea occur?

Back 14

1 week following treatment with chemotherapy

Front 15

CANCER

When does nausea and vomiting occur?

Back 15

12-24 hrs after first treatment

Front 16

CANCER

When does the bodies bone marrow start getting back to normal?

So when do blood counts recover?

Back 16

Around 21 days

Blood counts recover: between 21-28 days.

Front 17

CANCER

What drugs cause cardiac toxicity?

Back 17

Antracyclines

Front 18

CANCER

What drug causes pulmonary toxicity?

Back 18

Bleomycin

Front 19

CANCER

What drug causes nephrotoxicity?

Back 19

cis-DDP

Front 20

CANCER

What is the most important test to run on a patient receiving chemotherapy?

Back 20

Absolute neutrophil count

This is because segmented neutrophils and bands (immature neutrophils) are very important to fighting off bacterial infections.

Front 21

CANCER

Are there any acute toxic effects of chemotherapy?

Back 21

NO

Front 22

CANCER

Is the fall in platelets and WBC's acute when using chemotherapy? Explain

Back 22

No, it is not acute.

This is because the effect of chemotherapy is not on the formed elements of the blood but on the precursor cells in the bone marrow which are dividing. When chemotherapy is given the production of precursor cells or the platelets and the WBC's is temporarily halted but the circulating platelets and WBC's are not affected. It take about 1 week to see a decrease in production of PMN and platelets and bone marrow is back to normal about the third week following chemotherapy.

Front 23

CANCER
VIP VIP VIP

What is the formula for the absolute neutrophil count:

Why is the ANC so important?

Back 23

ANC = total white count x (fraction of PMN + fraction of bands)

ANC is important because if it fails below 500 you are at an increased risk of infection from bacteria in the gut. Bacteremia can occur. So any patient with a fever and ANC < 500 must be hospitalized and given broad spectrum antibiotics.

Front 24

CANCER

Which count is more affected in chemotherapy: PMN or platelets?

Back 24

PMN

but if platelets fall below 20,000 (rare) patient is at increased risk for hemorrhage and platelet transfusions are given.

Front 25

CANCER

How can you reduce the severity of myelosuppression when administering chemotherapy?

Back 25

Severity can be lessened with the use of granulocyte colony stimulating factor (G-CSF). This drug should be given 24hrs after each chemotherapy is given.

This drug will lessen myelosuppression but will not effect thrombocytopenia.

Front 26

CANCER

What is another drug that causes pulmonary toxicity?

Back 26

BCNU

Front 27

CANCER

If cumulative toxicity reversible or irreversible?

Back 27

Irreversible

Front 28

CANCER2

In general, what does the stage of the cancer tell us?

Back 28

The extent of disease at the time of diagnosis

Front 29

CANCER2

What is used to determine the stage of a cancer?

Back 29

1. PE
2. blood tests
3. imaging studies

Front 30

CANCER2

Who gets chemotherapy?

Back 30

1. someone with a cancer removed but who is believed to be at high risk of recurrance

2. someone with metastatic disease

3. someone with a large tumor burden before going into surgery so as to cause cytoreduction.

Front 31

CANCER2

What is the log kill hypothesis?

Back 31

Log Kill Hypothesis

The killing of CA cells by the chemotherapy durgs follows first order kinetics. The same fraction of CA cells is killed with each administration of chemotherapy (so we need multiple cycles of the drugs)

Front 32

CANCER2

What is the fractional cell kill?

Back 32

The fraction of cells killed with each administration of drugs. (it is never 100%)

Front 33

CANCER2

Can tumor regrowth in between cycles of chemotherapy occur?

Back 33

YES

Front 34

CANCER2

What are the five rules for creating a combination therapy?

Back 34

Combo therapy
1. each individual drug in the combo should have acitivity against the disease
2. the drugs should have non-overlapping toxicities (except for hairloss and myelosuppression, NV)
3. combine drugs with different MOA's
4. combine cell-cycle specific and cell-cycle non-specific drugs
5. drugs should be given at a maximally tolerated dose and schedule since there is a relationship between response rate and dose of chemotherapy administered. (Goldie-coleman hypothesis)

Front 35

CANCER2
VIP

Indicate how the Goldie-Coleman hypothesis supports the administration of chemotherapy to patients who have had a CA removed but are at risk of recurrence at a later date.

Back 35

If patients are at risk for recurrence chemotherapy must be administered initially so as to kill any micromets while they are still chemo-sensitive.

Front 36

CANCER2

In staging of CA's, do all CA grow from stage 1 to 2 to 3, etc?

Back 36

NO!! There is no orderly progression of stages. Can go from 1 to metastasis!