Pt 4 Chemo Drugs

Front 1

Monoclonal Abs:

"O" = ?
"U" = ?
"Xi" = ?
"Zu" = ?

Back 1

Murine (O)
Human (U)
Chimeric (Xi)
Humanized (Zu)

Front 2

Hypersensitivity and infusion-related reactions are greatest with ____MABs and least with ___MABs

Back 2

greatest with murine (O)

least with humanized (U)

Front 3

Most patients receiving MABs are premedicated with what?

What about the initial infusion rates?

Back 3

APAP and antihistamines

lower infusion rate for initial doses

Front 4

MAB general MOA
- mediate cell killing through ___ activation

_____ deliver chemo or radioactive particles to site of disease

Back 4

complement

immunoconjugates

Front 5

Gemtuzumab Ozogamicin
- anti-CD__?
-CD__ expressed on surface of leukemic blasts in > 80% of patients with ___?

- MOA =

Back 5

-CD-33
- AML

- MOA: binds to minor groove and leads to double strand breaks and cell death

Front 6

Gemtuzumab Ozogamicin

- indicated for?

- most severe toxicity
- other tox?

Back 6

- for elderly patients with cd33+ AML that have failed at least one chemo regimen

- myelosuppression
- tumor lysis syndrome, hepatotox

Front 7

RITUXIMAB

-_____ type of AB directed against CD___ found on surface of malignant ___ Cells

- FDA approved for ______ lymphomas

Infusion: start at ____ mg/h and max of ___ mg/h

Back 7

- chimeric, CD20, B cells
- refractory B-cell non-Hodgkin Lymphomas

- 50 mg/h - 400 mg/h

Front 8

IBRITUMOMAB TIUXETAN

- immunoconjugatethat consists of murine anti-CD___

Therapeutic Regimen is 2 steps
1. _____ is given to decrease # of circulating __ cells
2. ____ followed by ____ to deliver radiation to B cell expressing CD20

Back 8

-CD20

1. Rituximab, B cells
2. In-111 ibritumomab; Y-90-ibritumomab

Front 9

Ibritumomab Adverse Events include

Back 9

Infusion related rxns
Anaphylaxis
myelosuppression

Front 10

TOSITUMOMAB

- ____conjugated MAB for CD___
- combined with radioisotope ____

Back 10

- murine, CD20
- I-131

Front 11

Tositumomab

2 step regimen
- 1. _____________ to decrease circulating B cells
- 2. __________

Back 11

1. naked tositumomab (w/o I-131)
2. radioimmunoconjugate (with I-131)

Front 12

Tositumomab

Adverse effects

Back 12

Infusion-related rxn
Myelosuppression

Front 13

ALEMTUZUMAB

-Recombinant ____ MAB directed against CD__
- CD__ expressed on surface of___?

Back 13

- humanized, CD52
- B and T lymphocytes, natural killer cells, and macrophages

Front 14

Alemtuzumab

indicated for ____ in patients who have been treated with ____ agents and failed ____ therapy

Back 14

- B cell CLL, alkylating agents, fludarabine

Front 15

Alemtuzumab

Black Box Warning ____
- need to use prophylaxis for
1.
2.

Back 15

BBW- Severe infusion-related reactions, hematologic toxicity and opportunistic infections 1.

1. P. jirovecii pneumo (Bactrim BID 3x/week)
2. Herpes (Acyclovir for 6 months after Alem or until CD4 reaches 200 cells/mm3)

Front 16

CETUXIMAB

MOA: bind to extracellular domain of _____ on normal and tumor cells

Back 16

- EGFR (aka HER-1) - induces apoptosis and inhibits VEGF production

Front 17

Cetuximab

Adverse events

Back 17

- infusion related reactions
-acne-like rash
- fatigue
- GI complaints
- abdominal pain

Front 18

Trastuzumab

- Do you use it alone or in combo?

- Benefit demonstrated in ____+ breast cancer and given for a period of _____ in combo with chemo

Back 18

- both! Can be used as a single agent or in combo with PACLITAXEL

- HER2+, 1 year

Front 19

Trastuzumab

Most serious AEs:

Back 19

- cardiomyopathy
- infusion-related rxn
- hypersensitivity
- increased myelosupression

Front 20

Erlotinib & Gefitinib

- both are given how?

MOA: - selective _______ inhibitors block transduction pathway involved in ____, ____, ____

Back 20

- PO
- EGFR-tyrosine kinase; proliferation; survival; metastases

Front 21

Gefitinib is approved as mono or combo therapy?

what is it used for?

Back 21

- monotherapy

- inoperable NSCLG after failure of both platinum-based and docetaxel

Front 22

Erlotinib indicated for?

- used in _____ cancer combined with _____

- most common AE

Back 22

- 2nd line agent for locally advanced or metastatic NSCLG

- pancreatic, gemcitibine

- rash and diarrhea; warfarin increases INR

Front 23

Lapatinib

MOA: inhibits intracellular kinase domain of both _____ and ____

In Vitro shown to be active against ___ cancer cells

AEs?

Back 23

- EGFR, HER-2

- Breast

- QT prolongation, diarrhea, hepatotoxicity, rash

Front 24

VEGF, fibroblast growth factors, platelet-derived growth factor, TNFalpha, and keratinocyte growth factor are all examples of pro-_____ factors

Back 24

-pro-angiongenic

Front 25

Bevacizumab

- directed against circulating ____

- binds to the above and prevents the activation and promotion of ____

Back 25

- VEGF

- angiogenesis

Front 26

Bevacizumab

Approved in combo with:
1. ____ for tx of colorectal cancer
2. _____ and ____ for unresectable, locally advanced, recurrent or metastatic nonsquamous NSCLC

Back 26

1. 5-FU
2. Carboplatin, paclitaxel

Front 27

Bevacizumab

Most common AEs (black box for___?)

not recommended for use ____ days before major surgery

Back 27

- HTN, bleeding/thrombosis
black box warning for GI perforation

- 28 days

Front 28

Sunitinib & Sorafenib

- both approved for ___?

- Sunitinib approved for _____ tumors after ____ failures

Back 28

- advanced renal cell carcinoma

- GI stromal tumors, imatinib

Front 29

AEs for both Sunitinib and Sorafenib?

- AE for sunitinib?

- AE for Sorafenib?

Back 29

- both = diarrhea, rash, fatigue, HTN

- CHF

- Hand-foot syndrome

Front 30

Imatinib

MOA: selective inhibitor of TK activity of ____ gene, aka ____ chromosome

- this chromosome is the hallmark of ___?

- this involved translocation of chromosomes # __ & ___ between the _____ gene

Back 30

- BCR-ABL; Philly Chromosome (Ph)

- CML- chronic myeloid leukemia

-9,22, bcr-abl

Front 31

Imantinib

Standard treatment for newly diagnosed ____ and _____

AEs include?

Back 31

- Ph+ CML; c-KIT (CD117)+ GI stromal tumors

- fluid retention (pleural effusion, pericardial effusion, ascites) edema, SOB

Front 32

Dasatinib

-shares same binding site on ____ TK
-maintains clinical activity against ____ binding site that confer ___ resistance

Back 32

- bcr-abl
- bcr-abl; imatinib

Front 33

Dasatinib

AE include?

Back 33

myelosuppression, N/V, HA, fluid retention

Front 34

Bortezomib

MOA: ______ inhibitor

- approved for ___ and ___

Back 34

- proteosome

- multiple myeloma, mantle cell lymphoma

Front 35

Bortezomib

Most common AEs

Back 35

Asthenia (fatigue, malaise, weakness), Nausea, diarrhea, decreased appetite, GI complaints, myelosuppression

Front 36

Temsoriolimus

Mammalian target of _____

- binds to ____ and inhibits activity of ____ by blocking kinase activity

Back 36

- rapamycin (sirolimus) mTOR component of intracellular signaling pathways involved in cell growth and proliferation

- FKBP-12; mTOR

Front 37

Temsirolimus

- _____ inhibition suppresses production of proteins that regulate angiogenesis

- approved for?

- most common AEs

Back 37

-mTOR

- Renal cell carcinoma

- rash, fatigue, mucositis, nausea, edema, loss of appetite

Front 38

Thalidomide and Lenalidomind

- MOA thought to be through inhibition of ____?

- both approved for ____

Back 38

- angiogenesis

- multiple myeloma

Front 39

Thalidomide AEs?


Lenalidomide AEs?

Back 39

- somnolence, constipation, dizziness, orthostatic hypotention, rash, periph neurop

- neutropenia, thrombocytopenia, and thrombotic issues

Front 40

Interferons have what 3 types of activities?

INF MOAs?

Back 40

1. antiviral
2. antiproliferative
3. immunoregulatory

- increase activity of cytotoxic cells
- direct antiproliferative effects
- prolong cell cycle --> apoptosis
- inhibit angiogenesis
- increase expression of antigens on tumor cell surfaces

Front 41

This promotes B and T cell proliferation and differentiation

Also it initiates cytokine cascade with multiple interacting immunologic effects

Back 41

Interleukin-2

Front 42

Toxicity of IL-2 is related to what 3 things?

Most common AEs

Back 42

1. dose
2. route
3. duration of therapy

- hypOtension, fluid retention, renal dysfunction

Front 43

This implies that the patient is entirely free of disease and has the same life expectancy as a cancer free person

Back 43

Cure

Front 44

A Complete response (CR) is defined as?

Back 44

complete disappearance of all cancer w/o evidence of new disease for at least 1 month after treatment

Front 45

A partial response (PR) is defined as?

Back 45

30% or greater decrease in tumor size or other objective disease markers and no evidence of any new disease for at least a month

Front 46

Stable disease is defined as?

Back 46

Tumor stays the same size

Front 47

Progressive Disease is defined as?

Back 47

20% increase in tumor size or development of any new lesions while receiving treatment

Front 48

True or False?

Multiple Myelomas and leukemias are characterized by discrete measurable masses?

Back 48

False

- responses to these are measured by elimination of abnormal cells

Front 49

Lab values needed before starting chemo:

WBC?
ANC?
Platelet?

Chem panels?

Back 49

WBC > 3,000/mm3
ANC > 1,500/mm3
Plt > 100,000/mm3

Chem = renal and hepatic function

Front 50

Vinca alkaloids MOA?

cell cycle specific?

Back 50

mitotic spindle inhibitors

yes, M phase

Front 51

Dose limiting toxicity of vinorelebine and vinblastine?

Back 51

myelosuppression

Front 52

Dose limiting toxicity of vincristine?

Back 52

neurotoxicity

Front 53

Resistance to vinca alkaloids develop from what?

Back 53

P-glycoprotein mediated multi-drug resistance

Front 54

Taxanes (paclitaxel, docetaxel) MOA?

Cell cycle specific?

Back 54

Bind to mitotic spindle and promote stable yet dysfunctional tubules

M phase

Front 55

Resistance to taxanes due to:
1.
2.

Back 55

1. Alterations in tubulin or binding sites
2. PGP-mediated multi-drug resistance

Front 56

Adverse effects of docetaxel?

Back 56

myelosuppression, fluidretention, hypersensitivity

Front 57

Adverse effects of paclitaxel

Back 57

myelosuppression, neurotoxicity, hypersensitivity

Front 58

New form of paclitaxel is bound to what?

What is its adverse effect?

Back 58

Albumin (Nab-paclitaxel)

peripheral neuropathy

Front 59

Estramustine MOA?
- how is it unique?

Cell cycle specific?

Back 59

Combines alkylating agent (nor-nitrogen mustard) with hormone (estradiol)

binds to microtubule proteins and causes separation of the proteins from the microtubules causing their disassembly

M phase

Front 60

Topotecan and camptothecan inhibit topoisomerase I or II?

Back 60

topo I

Front 61

Tenoposide and etoposide inhibit topo I or II?

Back 61

topo II

Front 62

Topoisomerase inhibitors MOA?

Back 62

relieve torsional strain during DNA unwinding producing strand breaks

Front 63

Irinotecan and topotecan are analogs of what drug?

- why were they made?

- what active metabolite?

- topo I or II?

Back 63

camptothecan

- reduce toxicity and improve effect

- SN38 metabolite

- topo I

Front 64

3 methods of resistance to topo II inhibitors?

Back 64

- difference in topo II levels
- increased ability to repair strand breaks
- increased levels of PGP

Front 65

True or false: etoposide and teniposide are cross-resistant?

Back 65

True

Front 66

Etoposide and teniposide act on what stage(s) of the cell cycle?

Back 66

S or early G2 phase

Front 67

What is significant about mitoxantrone compared to the rest of the anthracene derivatives?

Back 67

It is an anthracenedione, not an anthracycline

has no sugar group bound to its 3 membered ring; other anthracenes are 4 memered rings.

Front 68

Anthracyclines are considered what type of class?

What should they really be called?

Back 68

Actual: antitumor antibiotics

Should be called intercalating topo inhibitors (topo II primarily)

Front 69

What do you have to have before starting an anthracycline ("rubicin") and why?

Back 69

EKG, cardiotoxicity due to free radical formation.

Note: free radical also causes extravasation injury

Front 70

How is significant about mitoxantrone from an adverse effect standpoint compared to the rest of the anthracyclines?

Back 70

less potential for free-radical formation.

Front 71

How are alkylating agents inactivated?

Back 71

hydrolysis; this is an important component of their elmination

Front 72

Resistance of alkylating agents is due to?
1.
2.
3.
4.

Back 72

1. increased DNA capabilities
2. decreased entry or increased exit from cells
3. increased inactivation of agents in cells
4. lack of cell mechanism to result in cell death following DNA damage

Front 73

Cyclophosphamide and Ifosfamide

- both are what type of derivatives?
- which one is a prodrug?

Back 73

- nitrogen mustards
- both are prodrugs

Front 74

This metabolite of cyclo and ifosfamide has little antitumor activity and is responsible for ______?

Back 74

Acrolein; hemorrhagic cystitis

Front 75

Carmustine (BCNU) and Lomustine are in which class?

what properties make them special?

Back 75

nitrosureas

- lipophilicity; ability to cross BBB

Front 76

True or false: lomustine is available as a drug-impregnated biodegradable wafer for brain tumors?

Back 76

False, its carmustine

Front 77

These agents are considered non-classic alkylating agents

Back 77

- procarbazine
- dacarbazine
- temozolomide

Front 78

______ and ______ undergo demethylation to the active intermediate MTIC causing methylation of guanine?

Back 78

dacarbazine and temozolomide

Front 79

True or false: temozolomide needs to be processed via the liver prior to exerting activity?

Back 79

False

dacarbazine does, however

Front 80

How must dacarbazine be given?

does it get to the CNS well?

Back 80

- IV

- NO!

Front 81

How is temozolomide given?

does it get to the CNS well?

Back 81

- PO

- YES!

Front 82

Cytotoxicity of the platinum derivatives depends on
1. binding to DNA and formation of ____?

2. adducts between neighboring ____s?

Back 82

1. intrastrand cross-links

2. guanines

Front 83

Cytotoxic form of cisplatin is what type of species?

____ groups replace 2 chloride groups

Back 83

- aquated

- hydroxyl groups or water

Front 84

Is the aqated species of cisplatin responsible for efficacy or toxicity?

Back 84

both!

Front 85

True or false: carboplatin undergoes aquation at a slower rate then cisplatin?

Back 85

true

Front 86

Resistance of platinum compounds occurs through
1.
2.
3.

Back 86

1. ability to repair DNA damage

2. increased levels of glutathione

3. altered uptake into cells

Front 87

Adverse Effects of platinum species (class effects)

Back 87

"NOPE-A"

Nephrotoxicity
Ototoxicity
Peripheral Neuropathy
Emesis
Anemia

Front 88

AE of carboplatin is limited by what toxicity?

Back 88

hematologic toxicity (quiz question)

Front 89

What heavy metal compound requires hydration before and after treatment?

Back 89

cisplatin

Front 90

AEs of oxalipatin
1. moderate ____ potential
2.
3. unique _____ induced neuropathies

Back 90

1. ematogenic
2. peripheral neuropathy
3. cold-induced

Front 91

Endocrine therapy is an option for cancers under what type of control?

Back 91

Gonadal hormonal
- breast
-prostate
-endometrial

Front 92

______ are useful anticancer agents because of their lymphotoxic effects?

Back 92

corticosteroids

Front 93

Corticosteroids are used primarily for what types of malignancies?

Back 93

hematologic --> lymphoma, lymphocytic, multiple myelomas

also as supportive care

Front 94

MOA of bleomycin

cell cycle stage(s)?

Back 94

Antitumor antibiotic that breaks DNA strands leading to formation of free radical

G2 and M phases

Front 95

Bleomycin's cytotoxicity depends on binding to ______ complex to DNA

what does this complex do?

Back 95

bleomycin-iron complex

reduce molecular oxygen to free radicals that cause SINGLE STRAND breaks

Front 96

Bleomycin is inactivated by what enzyme?

the enzyme is not highly concentrated in ____ and ____ and are sites of toxicities

Back 96

aminohydrolase

skin and lung
- pulmonary fibrosis

Front 97

Hydroxyurea MOA?

Cell cycle phase(s)?

Back 97

inhibits ribonucleotide reductase producing abnormally short DNA strands

(hates Rock and Roll like Gemcitibine)

S phase

Front 98

Hydroxyurea is used primarily why?

Back 98

To cause rapid decline in WBC prior to starting more potent chemo drugs

Front 99

An organic, well-known poison antineoplastic drug used for acute promyelocytic leukemia (APL)

Back 99

arsenic trioxide

Front 100

Arsenic trioxide MOA

Back 100

induces growth progression of cancerous cell into mature, more normal cells and INDUCES APOPTOSIS

Front 101

5 FU must be converted to what active metabolite?

this metabolite interferes with _____

Back 101

FdUMP

thymidine synthase

Front 102

5 FU has another metabolite _____ that is incorporated into ____ and interferes with its function

Back 102

5FU-triphosphate nucleotides

incorporated into RNA

Front 103

Capecitabine is an analog of _____

prodrug of ____

how is it given?

Back 103

- uracil
- 5FU
higher levels of selectivity

- PO, BID

Front 104

Cytarabine (ara-C) is an arabinose analog of ____

Back 104

- cytosine

Front 105

cytarabine active form is ____?

MOA?

Back 105

ara-CTP

- inhibits DNA polymerase and produces chain termination

Front 106

Most common AE of cytarabine

Risk of toxicity is correlated with advanced ____ and _____ dysfunction

Back 106

- cerebellar syndrome: dysarthria, nystagmus, ataxia

- advanced age and renal dysfunction

Front 107

_____ is a fluorine-substituted deoxycytidine analog related to cytarabine

Back 107

- Gemcitabine

Front 108

Gemcitabine MOA?

Back 108

- similar to cytarabine
inhibits ribonucleotide reductase

Front 109

Compared to cytarabine, gemcitabine achieves intracellular concentration ____ times higher

- what is this due to?

Back 109

20 x

- increased penetration of cell membranes
-greater affinity for deoxycytidine kinase

Front 110

Cytidine analogs _____ and _____ are approved treatment of myelodyspastic syndroms (MDS)

Back 110

azacytidine & decitabine

- MDS is a disorder of hematopoietic cell maturation that can progress to AML

Front 111

Azacytidine and Decitabine MOA?

Primary toxicity?

Back 111

- incorporate into DNA and inhibit DNA methyltransferase leading to hypomethylation of DNA; especially in actively dividing cells

- myelosuppression

Front 112

6 mercaptopurine and 6- thioguanine MOA?

cross resistant?

Back 112

- both rapidly converted to ribonucleotides that inhibit purine biosynthesis

- you bet they are!

Front 113

6-MP depends on ______ for initial oxidation step

6MP doses must be reduced with _____ is given concurrently?

Back 113

- xanthine oxidase

- allopurinol (decrease by 50%)

Front 114

Fludarabine MOA?

Back 114

interferes with DNA pol and causes chain termination; also inhibits RNA transcription

Front 115

Fludarabine AEs?

Back 115

myelosuppression

immunosuppression- REQUIRES PROPHYLACTIC ANTIBIOTICS AND ANTIVIRALS!!!!

Front 116

True or false: cladarabine affect actively dividing cells only

Back 116

false: both actively dividing and resting cancer cells

Front 117

Cladarabine is resistant to inactivation by _______ and is triphosphorylated to an active form thats incorporated into DNA. Results in ______

Back 117

- adenosine deaminase

- chain termination and inhibited DNA synthesis

Front 118

Pentostatin MOA?

Back 118

- potent adenosine deaminase inhibitor
(different from cladarabine)

Front 119

Adenosine deaminase is found in high concentrations in what tissue type?

Back 119

- lymphatic

also, its critical in purine base metabolism

Front 120

MTX is transported via what type of transport system?

Back 120

- active, but in high doses passive diffusion may overcome tumor cell resistance

Front 121

Resistance to antifolates like MTX can be caused by amplification of what?

Back 121

dihydrofolate reductase (DHFR)

Front 122

AEs of MTX are dependent on time or concentration?

Back 122

both!

Front 123

Rescue treatment of MTX toxicity?

Must be given until MTX levels fall to what #?

Back 123

leucovorin

<5 x 10^8 M

Front 124

Pemetrexed MOA?

Back 124

inhibits DHFR, thymidine synthase, glycinamide ribonucleotide forymyltransferase

- decreased risk of resistance compared to MTX

Front 125

Pemetrexed AEs

what do you have to give?

Back 125

severe hematologic toxicities (associated with increased cystathionine or homycysteine)

have to give B12 and folic acid to decreases cyst and homocyst

Front 126

Treatment for neutropenia

Back 126

colony stimulating factors

Front 127

Treatment for thrombocytopenia

Back 127

platelet transfusion

Front 128

How do you calculate ANC?

what is neutropenia defined as?

Back 128

%neutrophils (segs + bands) x WBC

ANC <500

Front 129

Treatment options for anemia

Back 129

RBC transfusion

Epoetin alfa

Darbepoetin alfa (3x longer t1/2)