5. Cancer Pharmacology Part 2

Question 1

What is the MC form of cancer in children, whose treatment with MTX dramatically increased length of survival, MTX is an antimetabolite/folate and is rescued by follinic acid/ leucovorin with SE including myelosuppression, D/N/V and causes secondary cancer such as AML?

Answer 1

Acute Lymphoblastic Leukemia

Question 2

6-mercaptopurine, cyclophosphamide, vincristine, and daunorubicin are all active against Acute Lymphoblastic Leukemia ALL, a combination of what two drugs plus one of the other agents listed is used to induce remission- 90% do with minimal toxicity?

Answer 2

Vincristine, Prednisone and one other agent listed

Question 3

Note: predinose causes inhibition of cytokine production, alteration of oncogene expression, cell cycle arrest and APOPTOSIS so it is GOOD to kill tumor cells and proliferation

Answer 3

HAHAH

Question 4

Circulating leukemic cells migrate to sanctuary sites located in the brain and testes, prophylaxis with what intrathecally is used to prevent CNS leukemia which is associated with a major mechanism of relapse?

Answer 4

Methotrexate

Question 5

What leukemia is the most common in adults, need intensive support care during the period of chem induction- such as platelet transfusions to prevent bleeding, granulocyte colony stimulating factor, filgrastim*, to shorten periods of neutropenia and abx to combat infections?

Answer 5

Acute Myelogenous Leukemia AML

Question 6

Acute Myelogenous Leukemia AML is best treated with what agent which is most active for AML, and is best used in combination with an athracycline such as idarubicin, in which we seen complete remission in 70% of patients?

Answer 6

Cytarabine** + Idarubicin

Question 7

Acute Myelogenous Leukemia AML remission is achieved by allogenic bone marrow transplantation preceded by high dose chemo and total body irradiation followed by immunosuppression- cures 35%, pts over 60 respond less well to chemo, after remission is acheived, consolidation chemo (after tx) is required to maintain remission and induce a cure, using cytarabine OR what?

Answer 7

Hematopoeitic cell transplantation

Question 8

What leukemia is due to Bcr-Abl fusion oncoprotein aka philadelphia chr t(9:22) - seen in 90-90% of cases, the translocation results in constant expression of bcr-abl oncoprotein = growth, goals of tx include reduce granulocytes to NL levels, raise hemoglobin [] to NL, and relieve disease sx?

Answer 8

Chronic Myelogenous Leukemia CML

Question 9

What is the standard first line therapy in previously untreated patients with Chronic Myelogenous Leukemia CML, in which nearly all pts treated with it exhibit a complete hematologic response and 50% pts show a COMPLETE cytogenetic resopnse?

Answer 9

Imatinib

Question 10

Dasatinib and Nilotinib were initially approved for pts who were intolerant or resistant to imatinib but now both are indicated as first line treatment of CML, what drug specifically mentioned, along with other oral alkylating agents are effective in tx this disease?

Answer 10

Busulfan

Question 11

Chronic Lymphocytic Leukemia (CLL) is MC treated with chlorambucil and cyclophosphamide alkylating agents, chlorambucil is usually combined with prednisone, bendamustine is also approved as a monotherapy or in combo with prednisone. Dr Sheehy wants us to know COP and CHOP tx for CLL, what drugs are they?

Answer 11

COP: Cyclophosphamide/vincristine/prednisone
CHOP: Cyclophosphamide/doxorubicin/vincristine/prednisone

In COP: O=vincristine= Oncovin
in CHOP: H = doxorubicin

Question 12

CLL is also effectively treated with what monotherapy, or in combinationg with cyclophosphamide and mitoxantrone or it is combined with rituximab which enhances chemo when there is resisitance?

Answer 12

Fludarabine

Question 13

Hodkin’s Lymphoma treatment involves a complete staging evaluation before treatment can be formulated, for Stage I and IIA, tx includes combination therapy with chemo and field radiation to LN, the chemo used is ABVD, which are what 4 agents in which 60% are cured?

Answer 13

A-doxorubicin
Bleomycin
Vinblastine
Dacarbazine
***more effective, less toxic than MOPP - infertility and 2nd malig

Question 14

Hodkin’s Lymphoma for advanced stage III and IV, ABVD treatment is first line followed by sanford V which includes doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, eoposide and prednisone followed by radiation, and 3rd line is MOPP?

Answer 14

Mechlorethamine
Vincristine
Procarbazine
Prednisone
-high complete responses (80%), but more toxic--> infertility and 2ndary malignancies

Question 15

Non-Hodgkin’s Lymphoma (diffuse) is tx with combination chemotherapy CHOP (cyclophosphamide-doxorubicin-vincristine-prednisone) is the best initial treatment, what agent is added for BEST tx, shows increased response rate, disease free survival and overall survival versus CHOP alone?

Answer 15

R-CHOP w/ Rituximab

Question 16

Non-Hodgkin’s Lymphoma nodular (follicular) is treated with initiation of chemotherapy at the onset of symptoms, ‘watchful waiting’ and can use either bendamustine + rituximab or?

Answer 16

R-CHOP

Question 17

Multiple myeloma- most pts are symptomatic at time of initial diagnosis- requires cytotoxic chemotherapy by using MP protocol known as what two drugs, which is the standard regimen for 30 years- 40% respond?

Answer 17

Melphalan + Prednisone

Question 18

Stage I breast cancer is small primary tumor and negative LN so treated with sx alone. StageII breast cancer is node positive (1-3nodes), high risk of both local and systemic recurrence so post sx use adjuvant chemo to reduce relapse/prolong survival— CMF = cyclophosphamide, MTX, 5-fluorouracil or FAC which consists of?

Answer 18

5-Fluorouracil
doxorubicin
cyclophosphamide

Question 19

Prostate cancer is first treated with hormone therapy, advanced prostate cancer becomes refractory to it, mitoxantrone and prednisone is approved for this situation, provides palliation in those experiencing bone pain… What two drugs are the standard of care for hormone refractory prostate cancer*****?2

Answer 19

Docetaxel + Prednisone

Question 20

High risk stage II and II colorectal cancer are candidates for adjuvant chemo, either with XELOX = capecitabine (xeloda) + oxaliplatin or FOLFOX which is what 3, these are used q 6 months following surgical resection, reduces recurrence rate by 35%, improves pt survival?

Answer 20

FOLFOX= Folinic acid (leucovorin) + 5FU (which is metabolized to fdUMP, FUTP, FdUTP), and oxaliplatin

NOTE: Capecitabine is a prodrug metabolized to 5FU

Question 21

For metastatic colorectal cancer FOLFIRI is used which is folinic acid, +5FU + irinotecan, ziv-aflibercept added if progression has been observed with oxaliplatin, the most effective treatment is FOLFOX or FOLFIRI plus bevacizumab, or panitumumab/ ?

Answer 21

Cetuximab

TAS-102 approved from chemo refractory disease - limited by sig toxicities, clinical efficacy and low response rates

Question 22

Adjuvant platinum-based chemotherapy provides survival benefit in patients with pathologic non-small cell lung cancer NSCLC stage Ib, II, IIIA, Bevacizumab in combo with carboplatin and paclitaxel are used in pts with good performance status and what histology?

Answer 22

Non-squamous histology

Question 23

In patients with NSCLC who are not good candidates for bevacizumab or a squamous cell histology is present, treat with cisplatin or carboplatin + cetuximab, maintenance chemo is what agent, which is used in patients that have stabilized after four cycles of platinum-based first line chemo?

Answer 23

Premetrexed

Question 24

If molecular testing is done on NSCLC, there are certain agents used for different situations, for example, which is first line therapy in advanced NSCLC patients with sensitizing EGFR mutations- exon 19 deletions or exon 21 (L858R) substitution mutations?

Answer 24

Erlotinib

Question 25

If molecular testing is done on NSCLC, there are certain agents used for different situations, for example, which is first line therapy of metastatic NSCLC whos tumors have EGFR exon 19 deletions or exon 21 mutations?

Answer 25

Afatinib

Question 26

If molecular testing is done on NSCLC, there are certain agents used for different situations, for example, which is first line therapy for metastatic EGFR t790M-mutant NSCLC following progression on or after EGFR TKI therapy, overcomes resistance from T790M gatekeeper mutation?

Answer 26

Osimertinib

Question 27

NSCLC- squamous cell version is responsive to platinum based chemo, superior clinical activity achieved when cisplatin and gemcitabine are combined wth necitumumab, what is a PD1 inhibitor for use in cancers that have progressed on or after standard platinum based chemotherapy?

Answer 27

Nivolumab

Question 28

Small cell lung cancer SCLC is initially sensitive to platinum based combination regimens, drug resistance develops in nearly all patients with extensive disease, if dx early- it is curable using combined chemotherapy and radiation therapy, the common combination is cisplatin and etoposide or cisplatin and?

Answer 28

irinotecan

*Topotecan is second line in pt that have failed platinum based regimen

Question 29

In a majority of patients ovarian cancer remains occult, becomes symptomatic only after metastasis to peritoneal cavity–> malignant ascites, stage I is tx with whole abdomen radiotherapy and chemo combo cisplatin and cyclophosphamide, Stage III/IV is carboplatin + paclitaxel, recurrent disease can be treated with topotecan or?

Answer 29

liposomal doxorubicin as monotherapy

Question 30

Chemotherapy is recommended for patients with stage IIC or III seminomas and nonseminomatous disease, 90% of pts respond to chemo with complete remission (70-80%), a combo of 3 agents are used— PEB which include?

Answer 30

Cisplatin (Platinol)
Etoposide
Bleomycin
-used in high risk disease

Question 31

Melanoma once metastasized is difficult to treat- dacarbazine, temozolomide and cisplatin are most active cytotoxic agents, but response rate to these is low, biologic agents such as IFNa and IL2 have greater activity, what two -mabs are approved for unresectable metastatic MM as monotherapy- BRAF V600E mutations commonly present?

Answer 31

Nivolumab

Pembrolizumab

Question 32

Nitrosureas are most active against brain cancer because they cross the BBB due to their lipophilicity, carmustine used as a single agent is a treatment, PCV procarbazine + lomustine +vincristine is another regimen, what -mab alone or in combo with chemo has documented clinical activity in adult GBM?

Answer 32

Bevacizumab

Question 33

As a rule, large and older solid tumors are more difficult to eradicate when chemotherapy is started, what of the following tumor based properties explains best the reason for this chemotherapeutic limitation?

Answer 33

Growth fraction slows; more cells enter Go so less effective

Question 34

As a rule, large and older solid tumors are more difficult to eradicate when chemotherapy is started, knowing what you know from question 1- (Growth fraction slows; more cells enter Go so less effective), which of the following chemotherapeutics would be best at killing this type of tumor?

Answer 34

Ziv-aflibercept because doesnt depend on cell needing to be rapidly proliferating

Question 35

The following is the MOA of which drug used to treat Hodgkin’s lymphoma, MOA: alkylates DNA, causing cross links between parallel DNA strands?

Answer 35

Mechlorethamine

Question 36

Match the following MOA with the correct drug...
doxorubicin-
bleomycin- 
vinblastine-
decarbazepine-
topoisomerase II inhib= free rads
inhibits tubulin polymerase
alkylating agent
DNA strand break (single)= free rads

Answer 36

doxorubicin-topoisomerase II inhib= free rads
bleomycin-DNA strand break (single)= free rads
vinblastine-inhibits tubulin polymerase
decarbazepine-alkylating agent

Question 37

Testicular cancer is being treated with PEB chemo regimen, the patient then develops high frequency hearing loss, and experiences declining renal function, what drug is the most likely cause?

Answer 37

Cisplatin - to avoid renal toxicity, give NL saline before giving cisplatin!