Chemotherapy Flashcards
(212 cards)
1
Q
Cyclophosphamide MOA
A
[Bifunctionally Alkylates (via Phosphoramide Mustard) N7 of [DNA Guanine]–> forms inter and intrastrand crosslinks
2
Q
Is Cyclophosphamide CCS or CCNS?
A
CCNS
3
Q
Cyclophosphamide SE (3)
A
Hematuria
Myelosuppression
NVH
4
Q
Cyclophosphamide Indications (2)
A
- Non-Hodgkins Lymphoma
- Breast CA
5
Q
Ifosfamide MOA
A
Monofunctionally Alkylates N7 of [DNA Guanine]
6
Q
Is Ifosfamide CCS or CCNS?
A
CCNS
7
Q
Ifosfamide SE (4)
A
- Hematuria –> Hemorrhagic Cystitis
- [Myelosuppression DL (dose limiting)]
- [Lethargy & Confusion @ High dose]
- NVH
8
Q
Ifosfamide Indication (2)
A
(Relapsed) Testicular CA
Sarcoma
9
Q
Temozolomide MOA
A
Monofunctionally Methylates DNA
10
Q
Is Temozolomide CCS or CCNS?
A
CCNS
11
Q
Temozolomide SE (3)
A
Myelosuppression
NVH
[Pneumocystis PNA when given prolonged]
12
Q
Temozolomide Indication
A
[Glioblastoma (1° Brain Tumor)]
13
Q
[Cis-DDPlatinum] MOA
A
Bifunctionally Alkylates DNA
14
Q
Is [Cis-DDPlatinum] CCS or CCNS?
A
CCNS
15
Q
[Cis-DDPlatinum] Considerations (2)
A
- Give with Hydration & [mannitol diuresis] = Chloruresis
- Dose reduction for Renal Insufficient pts
16
Q
[Cis-DDPlatinum] Indications (6)
A
- Testicular CA: CURATIVE
- Ovarian CA
- Bladder CA
- SOLC
- Non-SOLC
- Head & Neck CA
17
Q
Carboplatin MOA
A
Bifunctionally Alkylates DNA
18
Q
Is Carboplatin CCS or CCNS?
A
CCNS
19
Q
Carboplatin SE
A
[Myelosuppression DL]
20
Q
Carboplatin Indication (6)
A
Same as [cis-DDPlatinum]
21
Q
What is the dosing of Carboplatin based on? (2) How easy is it to administer?
A
Creatinine Clearance and AUC Target; Easy to administer
22
Q
Oxaliplatin MOA
A
Bifunctionally Alkylates DNA
23
Q
Is Oxaliplatin CCS or CCNS?
A
CCNS
24
Q
Oxaliplatin SE (3)
A
“O O O how mya gets on my nerves”
- [Acute Cold induced Neuropathy DL]
- [Chronic Sensory Neuropathy DL]
- Myelosuppression
25
Oxaliplatin Indication
GI CA (**cOlOrectal** vs. gastric vs. pancreas)
## Footnote
***Doubles Survival in Metastatic cOlOrectal CA***
26
Vincristine MOA
Prevents Tubulin polymerization
27
Is Vincristine CCS or CCNS?
CCS (M phase)
28
Vincristine SE (2)
1. [Neuropathy DL]
2. Vesicant
29
Vincristine Indications (2)
"Cristy helps *ALL* the *Non* Kids"
[Non-Hodgkin's Lymphoma]
ALL- Acute Lymphoblastic Leukemia
30
[T or F] Vincristine does NOT cause myelosuppression
TRUE
31
Which pts require dose reduction with Vincristine AND VinBLastine?
Jaundice pts (elevated bilirubin); since these drugs are excreted via bile
32
VinBLastine MOA
Same as Vincristine (Prevents Tubulin Polymerization)
33
Is VinBLastine CCS or CCNS?
CCS (M phase)
34
VinBLastine SE (2)
Myelosuppression
[Vesicant Blistering agent]
35
VinBLastine Indications (2)
B for Boob Area
## Footnote
Lung CA
Breast CA
36
Paclitaxel MOA
Prevents Tubulin **Disassembly**
37
Is Paclitaxel CCS or CCNS?
CCS (M phase)
38
Paclitaxel SE (6)
**VHIMMS**
1. **S**ensory Neuropathy
2. [**M**yelosuppression DL] & **M**yalgia
3. **I**nfusion rxn from rxn to solvent
4. [**V**esicant Blistering Agent]
5. **H**airLoss
39
Paclitaxel Indications (4)
Non-SOLC
Breast CA
Ovarian CA
Gastroesophageal CA
40
Pts taking Paclitaxel should be premedicated with ____ (3)
Steroids
Diphenhydramine
H2 Blockers
41
Which pts require dose reduction with Paclitaxel?
Hepatic Dysfunction pts
42
Etoposide MOA
E*2*oposide
[Topoisomeriase *2* inhibitor] --\> Double stranded breaks in DNA
43
Is Etoposide CCS or CCNS?
CCS (S - G2)
44
Etoposide SE (3)
E2oposide made *Mya* and *Leuk* *Nauseous*
## Footnote
[Myelosuppression DL]
Leukemogenic (Leukemia promotor)
NVH (Nausea/Vomiting/Hairloss)
45
Etoposide Indications (3)
Testicular CA
Lymphoma
SOLC
46
Which pts require dose reduction with Etoposide? (2)
Hepatic AND Renal Dysfunction pts
47
Doxorubicin MOA
[Topoisomeriase 2 inhibitor] --\> Double stranded **intercalations** in DNA base pairs
48
Is Doxorubicin CCS or CCNS?
CC**N**S
49
Doxorubicin SE (5)
1. Myelosuppression: Dose Limiting
2. Congestive Cardiomyopathy! (Schedule dependent cumulative)
3. [Vesicant Blistering Agent]
4. NVH
5. Stomatitis
50
Doxorubicin Indications (5)
*Rubi* **S**ays **H**er **L**ove **B**eats **N**eoplasia!
## Footnote
**B**reast CA
**L**eukemia
**S**arcoma
**H**odgkin's Lymphoma
**N**on-Hodgkin's Lymphoma
51
Which pts require dose reduction with Doxorubicin?
Jaundice pts (Doxo is metabolized by Liver)
52
Irinotecan MOA
[Topoisomeriase 1 inhibitor] --\> single stranded breaks in DNA
53
Is Irinotecan CCS or CCNS?
CC**N**S; Bioactivated
54
Irinotecan SE (5)
[Myelosuppression DL (dose limiting)]
[Acute Cholinergic Diarrhea (tx: atropine)]
[Late Secretory Diarrhea (tx: Imodium)]
NVH
Stomatitis
55
Irinotecan Indications
Colon CA
56
Which pts require dose reduction with Irinotecan and why?
Jaundice pts
since [hepatic UGT1-A1] clears [glucuronidation of Irinotecan] _along with_ bile. A Jaundice pt indicates [hepatic UGT1-A1] underexpression
57
Bleomycin MOA
Binds to iron and then --\>binds to DNA--\> [single **and** double DNA breaks]
58
Is Bleomycin CCS or CCNS?
CCS (G2-M phase)
59
Bleomycin SE (6)
"Bleomycin will start to smell like **P**oop, **F**art & **HASH**"
1. [**P**ulm Tox DL] (lungs lack Bleomycin hydrolase)
2. **H**yperpigmentation
3. **S**tomatitis
4. **H**airLoss
5. **F**ever & Chills
6. **A**naphylaxis with 1st dose in Lymphoma pts
60
Bleomycin Indications
Testicular CA
61
Pts taking Bleomycin should avoid \_\_\_\_\_\_
[High inspired concentrations of O2]
62
[T or F] Bleomycin causes myelosuppression
FALSE
63
Prednisone CA Indications (2)
Dosage?
**At HIGH DOSES ( \>100 mg/day):**
Lymphoma (Hodgkins and Non-Hodgkins)
Multiple Myeloma
64
Dexamethasone CA Indications (3)
1. Reduces Cerebral Edema
2. Spinal Cord Compression initial tx
3. Chemotherapy-Emesis (used with other agents)
65
Tamoxifen Indication
Pre AND POSTMenopausal Breast CA that are (ER/PR +).
Tx and Px
66
Tamoxifen SE (6)
* Endometrial Malignant Neoplasia (includes Polyps) = **no administration duration \> 5 years**
* Cataracts
* PE
* Hot Flashes
* Amenorrhea
* Vaginal Discharge
67
Tamoxifen MOA
SERM
E2 modulator in Endometrium; E2 **B**locker in **B**reast
68
Anastrozole MOA
Aromatase inhibitor
69
Anastrozole SE
[Fractures & Arthralgia]
70
Anastrozole Indications
[**ER+** Breast CA (Tx and Px)]
71
Flutamide MOA
[Androgen R Blocker] --\> prevents DHT & Testosterone from binding
72
Flutamide SE (5)
- Hepatotoxicity
- Hematopoietic disorders
- Rash
- Constitutional (HA/Nausea)
-Diarrhea
73
Flutamide Indications (2)
Metastatic Prostate CA
BPH
74
How can Flutamide be used to prevent SE from Leuprolide
Pretx with Flutamide can block Flare rxn that occurs when taking [GnRH R agonist]
75
Leuprolide MOA
GnRH R agonist
76
Leuprolide Indication (4)
1. Endometriosis & Uterine Fibroids
2. Central Precocious Puberty
3. Keeps LH surge low --\> multiple mature oocytes for reproductive technology
4. [Androgen dependent Prostate CA] adjunct
77
What happens initially when giving Leuprolide? How is this circumvented?
Exacerbation of Prostate CA & Bone pain initially, 2° to [FSH & LH Flare].
Pretx with [Flutamide 2-4 Wks prior] can prevent this
78
Methotrexate MOA
After being polyglutamated (along with folic acid) it Reversibly Binds and inhibits [Dihydrofolate Reductase] --\> [INC Dihydrofolate] and [DEC Tetrahydrofolate].
Since Tetrahydrofolate is associated with thymidylate synthesis and is a [carbon donor for purine ring] --\> DEC DNA synthesis
*Enters cell via folate carrier protein*
79
Is Methotrexate CCS or CCNS?
CCS (S phase)
80
Methotrexate Indications (6)
1. Brain Tumor - HIGH IV DOSES
2. [Meningitis: carcinomatous vs. lymphomatous]
3. Leukemia
4. Lymphoma
5. Psoriasis
6. Rheumatoid Arthritis
81
Which pts require dose reduction with Methotrexate?
Renal Insufficiency pts
82
Methotrexate has been approved for ____ administration. Solubility of Methotrexate INC in ___ pH
Methotrexate has been approved for **intrathecal** (arachnoid space) administration--\>treats [Meningitis: carcinomatous vs. lymphomatous]
Solubility of Methotrexate INC in **Alkaline** pH. (So Alkalinizing Urine INC excretion)
83
What's the Volume of Distribution for Methotrexate?
Total Body Water
84
When does Methotrexate become toxic?
When co-administered with drugs that displace methotrexate from albumin **OR** DEC its urine excretion
85
Describe the High Dose Strategy for Methotrexate. Which organs is this useful in? (2)
Co-administer with [Leucovorin THF] (THF rescue) to prevent Myelosuppression SE.
Only for **Bone marrow** and **Intestine**
86
Cytarabine MOA
Converted to [ARA-CTP Triphosphate] --\> incorporates into DNA --\> inhibits chain elongation.
87
Is Cytarabine CCS or CCNS?
CCS (S phase)
88
Cytarabine SE (6)
[Cerebellar Tox with High dose--\>Coma--\>Death]
[Conjunctivitis with High Dose] (secreted in tears)
Hepatotoxic
[Myelosuppression DL]
NVH
Stomatitis
89
Cytarabine Indications (2)
Acute Myeloid Leukemia
## Footnote
*[3 Days of (Dauna vs. Doxo**Rubicin**)] --\> [7 days Cytarabine Continuous infusion]*
and
[Meningitis: carcinomatous vs. lymphomatous]
90
Cytarabine has \_\_\_\_dependent cytotoxicity. What is the Dose Regimen for treating [Acute Myeloid Leukemia]
**Schedule** Dependent Cytotoxicity
[3 Days of (Dauna vs. Doxo**Rubicin**)] --\> [7 days Cytarabine Continuous infusion]
91
[5-FluoroUracil] MOA (2)
1. Inhibits [Thymidylate Synthase]. Accumulation of FdUMP--\> [FdUMP + ch2THF] ALSO binds/inhibits [thymidylate synthase] --\> thymineless death
2. Sequential phosphorylation & incorporation into RNA & DNA
92
Is [5-Fluorouracil] CCS or CCNS?
CCS (S phase); Bioactivated
93
[5-**F**luoro**U**racil] SE (8)
5 **CHEMS** **C**an **D**estroy **H**air
1. [**M**yelosuppression: **mild**]
2. **S**tomatitis
3. **D**iarrhea - also w/ Capecitabine
4. **H**and-Foot syndrome -also w/ Capecitabine
5. [**H**yperpigmentation **with** photosensitivity]
6. [**C**oronary Vasopasm]
7. **E**piphora (Lacrimation)
8. **C**erebellar Ataxia
94
[5-FluoroUracil] Indications (4)
"**F U**r *Face*, ur *Breast* and ur *SixPack*. I'm *sensitive*! "
1. [Head & Neck] CA
2. Breast CA
3. GI CA
4. Radiation Sensitizer (concomitant with radiation tx)
95
Pts deficient in ______ are at greater risk of [5-**F**luoro**U**racil] Toxicity
**DihydroPyrimidine Dehydrogenase** (Auto recessive)
96
What is the oral prodrug of [5-**F**luoro**U**racil]
Capecitabine
(This is hydrolyzed by thymidine phosphorylase into 5FU inside the tumor)
97
[6-Mercaptopurine] MOA
[6-thioINOsinic acid] inhibits enzymes of [de novo purine synthesis] by incorporating into DNA
98
Is [6-Mercaptopurine] CCS or CCNS?
CCS (S phase); Bioactivated
99
[6-Mercaptopurine] SE
Myelosuppression DL
100
[6-Mercaptopurine] Indications
**ALL**-Acute Lymphoblastic Leukemia
101
Which pts require dose reduction with [6-Mercaptopurine], by how much and why?
Pts taking **Allopurinol** must have [6-Mercaptopurine] dose reduced by **50-75%**, since [6-Mercaptopurine] is inactivated by [Xanthine Oxidase]
102
Asparaginase MOA
Bacterial product that inhibits Asparagine Hydrolysis --\> Inhibits Protein synthesis
103
Asparaginase SE (4)
"Tht Asparagus made me feel like **TAPE**!"
* **T**hromboembolism (from DEC in AT3)
* **P**ancreatitis
* **E**levated Liver enzymes
* **A**llergic rxn
104
Asparaginase Indications
**ALL**- Acute Lymphoblastic Leukemia
105
Hydroxyurea MOA
Inhibits [Ribonucleotide Reductase] --\> inhibits [DNA thymine] synthesis
106
Hydroxyurea Indication
**Rapidly** DECREASES High [WBC *Blast* count] in pts with [Acute Myeloid Leukemia] and [Chronic Granulocytic Leukemia w/blast crisis]
107
Why is it dangerous for [Acute Myeloid Leukemia] pts to have High WBC counts?
High WBC counts can--\> **Leukostasis** in capillaries --\> Organ Damage and Death
108
Tretinoin MOA for CA
Induces terminal differentiation of leukemia cells
109
Describe the ____ syndrome caused by Tretinoin (3). What other SE occurs that's not in this syndrome
[**Retinoic Acid Differentiation Syndrome**]
Fever
Pulm infiltrates
Effusion (Pleural & Pericardial)
+
Dry Skin
110
Tretinoin Indications
Acute **Pro**myelocytic Leukemia
111
What type of compound is Tretinoin
All trans retinoic acid
112
[Arsenic Trioxide] MOA for CA
Allows Myeloid differentiation to continue and apoptosis to occur
113
[Arsenic Trioxide] SE (2)
[**Retinoic Acid Differentiation Syndrome**]
Prolonged QT
114
[Arsenic Trioxide] Indications
Acute **Pro**myelocytic Leukemia
115
Imatinib MOA
Inhibits BcrAbl, which is upstream and required for Tyrosine Kinase
## Footnote
*Tyrosine Kinase Inhibitor*
116
[Imatinib Mesylate] SE (5)
"Use **T**ough **MACE** to deal with Iman's SE!"
**E**dema
[**M**usculoskeletal Pain & Cramps]
[**A**nemia/Neutropenia/Thrombocytopenia]
**C**HF (rare)
DEC **T**hyroid Hormone (by INC clearance)
117
[Imatinib Mesylate] Indications (2)
*Iman* **C**aught my **GIST**
1. [**C**hronic Myelogenous Leukemia]
2. **GIST** (Gastrointestinal Stromal Tumor)
118
[Imatinib Mesylate] consideration
Metabolized by CYP3A4 system
119
Cetuximab MOA (2)
Inhibits [Epidermal Growth Factor Receptor]
and
**Sensitizes** cell to chemotherapy
120
Cetuximab SE (3)
"SE of a *Dusty*, *Ugly*, *Stankin**'* Tux"
* *Dusty* = Hypersensitivity (Rash)
* *Ugly* *DEC the Chick **Magn**et =* hypO**Mag**nesemia
* *Stinky smell* = Diarrhea
121
Cetuximab Indications (3)
"I got my *Tux* from **H** &/**L** **M**
## Footnote
**L**ung CA
**H**ead & Neck CA
[**M**etastatic _Wildtype_ **KRAS** and **NRAS** colorectal CA]
122
ERLotinib MOA
small molecule inhibitor of [Tyrosine Kinase Domain] associated with [EGFR: Epidermal growth factor receptor]
123
ERLotinib SE
Rash
124
**E**RLotinib Indications
[Metastatic Lung ADC **with EGFR activating mutation**]
125
Trastuzumab MOA
Binds to Extracell domain of [Her2Neu EGFR Receptor]
126
Trastuzumab SE
Cardiotoxic (mostly when coadministered with doxorubicin)
127
Trastuzumab Indications (2)
[(Her2Neu+) **Breast** CA]
[(Her2Neu+) **Gastric** CA]
128
Bevacizumab MOA
J *Bev* hates Veggies
Binds & inhibits VEGF
*Bev-a-Siz-zu-mab*
129
Bevacizumab SE (6)
J *Bev* **P**rays 4 a **CHAIR**
1. **H**TN
2. **P**rOteinuria
3. [**A**rterial Clots and bleeding]
4. **I**nfusion rxn
5. **C**olon Perforation
6. [**R**eversible POST LeukoEncephalopathy syndrome]
130
Bevacizumab Indications (2)
Lung CA
[Metastatic Colorectal CA]
131
Crizotinib MOA
Binds to [ALK- Anaplastic Lymphoma Kinase]
132
Crizotinib SE
Interstitial Lung Dz
133
Crizotinib Indications
[Metastatic Lung ADC with **ALK rearrangement**]
134
Vemurafenib Indication
[Melanoma with BRAFv600e mutation]
135
Explain which 2 tissue you can use [Leucovorin THF Rescue] and why this is?
**Bone Marrow** and **Intestine** do not contain [folylpolyglutamate synthetase] which means Methotrexate won't be polyglutamated(activated). Giving [Leucovorin THF] can resuce the normal cells in these tissue from [THF deficiency]
136
Why are [alkylating CA agents] cell cycle **Non**-specific (CCNS)?
They bind covalently to DNA producing inter and intrastrand crosslinkage
## Footnote
*This group = BisChoroethylamines*
137
List the 2 mechanisms of resistance for [Alkylating CA agents]
[Nucleotide excision repair enzymes]
[Alkylating agents] may incidentally bind to [Sulfur containing compounds]
138
Describe Bioactivation for [Cyclophosphamide & Ifosfamide]
Must be activated by [microsomal P450 enzymes] to Aldophosphamide --\> non-enzymatically cleaved to Acrolein and [phosphoramide mustard]. PM alkylates
139
How is the SE of Hematuria in Cyclophosphamide circumvented (3)?
1. [Administer in morning + Urinate frequently (6-8 glasses of water/day)]
2. Continuous bladder irrigation (when giving High dose)
3. Mesna (Uroprotective agent)
140
Cyclophosphamide Route of Admin (2)
IV vs. PO
141
[Chlorambucil & Melphalan] Indication (2)
*These are Alkylating Agents* that tx
## Footnote
**C**hronic Lymphocytic Leukemia
**M**ultiple Myeloma
142
Why does Ifosfamide HAVE to be co-administered with Mesna?
Ifosfamide SE= Hematuria --\> Hemorrhagic Cystitis
143
How does Mesna help prevent Hemorrhagic Cystitis?
Mesna is a monomer in urine that binds to alkylating agents and prevents their toxic urothelium effect
144
Describe the bioactivation of Temozolomide
Spontaneous hydrolysis to DNA reactive species --\> [monofunctionally methylates DNA]
145
What are Coordination Compounds?
Bifunctional Alkylating agents which bind to [N7 of Adenine & Guanine] while Pt is in 2+(from Aquation) --\> leaving groups are *cis*
146
[Cis-DDPlatinum] SE (5)
"*Cis*sys **N**ever **N**ever **N**ever **H**ave **M**oxie!"
1. **N**V
2. **N**europathy
3. hypO**M**agnesmia
4. [**H**igh Freq. Hearing loss]
5. **N**ephrotoxic
147
Is Carboplatin nephrotoxic?
NO
148
Name the Plant Alkaloids (4)
Vincristine: natural
VinBLastine: natural
Paclitaxel: natural
Etoposide: *SemiSynthetic*
149
Cabazitaxel Indication
Prostate CA
## Footnote
*Ca-Bazi-taxel*
150
Docetaxel Indication
Prostate CA
151
Why would [Albumind Bound Paclitaxel] be beneficial? (3)
SE = **VHIMMS**... you'd have less **I / M / S**
## Footnote
- No **I**nfusion rxn due to rxn against solvent
- Less [**M**yelosuppression DL]
- Less [**S**ensory Neuropathy]
152
Is Etoposide an intercalator or [non-intercalator]
Non-Intercalator
153
Function of Topoisomerase 1
Repairs **single** strand DNA breaks by relaxing strand and reannealing
154
Function of Topoisomerase 2
Repairs **DOUBLE** strand DNA breaks by relaxing strand and reannealing
155
Doxorubicin metabolism
**Liver metabolism** and then excreted as thiol adduct into bile
## Footnote
*Dose Reduction in Jaundice pts*
156
How does the [P-glycoprotein] cause [MultiDrug Resistance] and how do we cirvumvent this?
[P-glycoprotein]= membrand bound efflux pump that makes cells resistant to **[All Topo 2 inhibitors]** and **Tubulin inhibitors**
Giving these drugs as continuous infusions downregulates [P-glycoprotein efflux pump]
157
Name the drugs that block (reverse MDR) the [P-Glycoprotein Efflux Pump] (3)
**QVC** blocks the [P-G E P]
**Q**uinine
**V**erapamil
**C**yclosporine
158
Describe Cumulative Toxicity
Irreversible damage to small part of an organ, that with repeated admin--\>drug accumulation--\>specific *Total Dose* threshold --\> Total damage
159
Lifetime Dose of Doxorubicin should not exceed \_\_\_\_. This is to avoid \_\_\_\_\_
Lifetime Dose of Doxorubicin should not exceed **400**. This is to avoid **Congestive Cardiomyopathy**
160
Doxorubicin has schedule (*dependent* vs. *independent*) ______ cytotoxicity, which means what?
Doxorubicin has [schedule **independent** cytotoxicity], which means altering admin dose schedule won't affect cytotoxicity
161
A: MOA for why Doxorubicin causes Congestive Cardiomyopathy
B: How should it be administered to avoid this
A: Complexes with iron --\> **Free Radical Damage**
C: Admin over 96 hours to avoid high plasma levels, which is fine since Doxorubicin has [Schedule INdependent Cytotoxicity]
162
What events INC risk of Cardiotoxicity from anthracyclines? (2)
Prior Mediastinal radiation
Long standing Uncontrolled HTN
163
Doxorubicin and Daunomycin are in the same class. What's the difference? (2)
* Daunomycin is less cardiotoxic
* Daunomycin is **not** effective against solid tumors
164
Daunomycin Indication
Leukemia **but not solid tumors**
165
What are [Idarubicin & epirubicin] analogs of, and what are they used for?
Analogs of Doxorubicin. **Leukemia only**. Less Cardiotoxic than Doxorubicin.
166
What SE does all the anthracylcine drugs have in common?
Myelosuppression: dose Limiting
167
Name the 2 Demographics that have mutation which DEC Glucoronidation and which drug this puts them at risk for
Caucasian and Africans have INC risk of **Irinotecan** Tox
168
Topotecan is in the same class as ____ and is used for what?
Irinotecan;
Ovarian CA resistant to carboplatin & paclitaxel
169
Bleomycin Metabolism
Inactivated by [bleomycin hydrolase] in Liver & kidneys with 50% urine excretion
170
Lifetime Dose of Bleomycin should not exceed \_\_\_\_. This is to avoid \_\_\_\_\_
Lifetime Dose of Bleomycin should not exceed **400**. This is to avoid **Pulm Tox**
171
Tamoxifen Metabolism
Liver; metabolized --\> [4Hydroxytamoxifen]
172
[T or F] Anastrozole requires dose reduction in Liver or Renal Dysfunction pts
**FALSE**
Although Anastrozole is extensively metabolized by Liver, it does not require dose reduction
A for *A*lright in *A*ll pts
173
What are [Bicalutamide & Nilutamide] analogs of? What's the difference between them and the analog?
Analogs of Flutamide. They have Less Diarrhea
174
Leuprolide Route of Admin (2)
IM vs. Depot injections
175
What color is MTX and where is it excreted?
Yellow; Urine
176
Which drugs are Contraindicated with Methotrexate and why (4)
"No Maple **SAPP**, with my chex MTX"
1. **S**ulfonamides - highly protein bound
2. **A**SA - highly protein bound AND also interferes with excretion
3. **P**CN- highly protein bound AND also interferes with excretion
4. **P**robenacid blocks organic acid transport --\> interferes with excretion
177
[MTX SE - normal dose] (3)
1. [Myelosuppression DL]
2. NV
3. Stomatitis
178
SE of HIGH DOSE MTX Therapy (6)
* NOT Myelosuppression
but even so... **SERCH** for help!
* **S**tomatitis
* **E**nteritis
* **C**onjunctivitis
* **R**enal Failure
* **H**epatic Failure (rare)
179
Describe the [HIGH DOSE MTX with Leucovorin rescue] regimen (5 steps)
1st: [IV hydration + NaHCO3 to alkalinize urine]
2nd: Do not administer MTX unless urine pH\>7
3rd: Give MTX
4th: [IV vs. PO Leucovorin admin]
5th: Monitor MTX and stop when level is [\<5x10-7 at 48 hours]
180
Pemetrexed MOA
Antifolate that's polyglutamated after entering cell and then --\> inhibits thymidylate synthesis
181
Pemetrexed Indication (2)
*PeM*etrexed : *P*ul*M*
Lung CA
Mesothelioma
182
Pemetrexed SE (5)
***Mya****'s* PemP used his ***Hand*** to give her a ***R**ash***, [***Bloody Mouth***] &***Diarrhea***
[Myelosuppression DL] (*Mya*)
[Hand Foot Syndrome]
Rash
Stomatitis
Diarrhea
183
How can the [Myelosuppresion DL] SE of Pemetrexed be reduced?
Pretx with [Parenteral VitB12] and [PO Folic Acid]
184
Explain how long you should use Cytarabine and what this has to do with [Schedule dependent cytotoxicity]
Tumor needs to be exposed to Cytarabine for at least 4 hours, and since half life is short (2 hours), Cytarabine has [Schedule Dependent Cytotoxicity]
185
Cytarabine is a ___ \_\_\_\_ antimetabolite
Cytarabine is a **Cytosine Arabinoside** antimetabolite
186
What is the difference between Cytarabine and Gemcitabine?
Similar MOA to Cytarabine (including [Myelosuppression DL] SE) but can be used in palliative tx of Pancreatic vs. Lung CA
187
Describe the interaction between [5 FluroUracil] and Leucovorin when co-administered?
[5FU] + Leucovorin --\> INC 5FU Cytotoxicity
BUT
[Stomatitis and Diarrhea SE] will be worse!
188
Capecitabine [Route of Admin] and [Indications (2)]
Capecitabine is a **PO** drug that treats Breast and GI CA
189
Which analog of [6-Mercaptopurine] **can** be concomitantly given with Allopurinol?
**6-thioguanine** can be used at full dose with allopurinol (has no interaction with xanthine oxidase)
190
Methotrexate is a ______ analog
Methotrexate is a **Folic Acid** analog
191
[Imatinib Mesylate] Metabolism
CYP3A4 (avoid administering with St.john's Wort or grapefruit juice)
192
How is Cetuximab prescribed
[Chimeric monoclonal Ab given IV qweek or every other week] usually in combination with other chemo
193
Erlotinib Metabolism
CYP3A4 (avoid administering with St.john's Wort or grapefruit juice)
194
[Sorafenib, Pazopanib and Sunitinib] are _______ that have a SE of ______ (4). They all treat ____ CA, but Sorafenib can be used in ____ and Sunitinib in \_\_\_\_
[Sorafenib, Pazopanib and Sunitinib] are **[VEGF R tyrosine kinase inhibitors]** that have a SE of **[Hand foot syndrome, rash, HTN and Reversible POST leukoencephalopathy syndrome**] (4).
They all treat **[Clear Renal Cell** CA], but Sorafenib can be used in **Hepatocellular CA** and Sunitinib in **[Pancreatic Neuroendocrine CA & GI Stromal tumors]**
195
Name the 2 other antibodies in the Trastuzumab class
"*Tra* to *Lap* *Per*" (Try to Lap Her)
Lapatinib (small molecular inhibitor of RTK)
Pertuzumab (Ab against Her2Neu)
196
CA localized to organ of origin are treated with ____ therapies such as ____ (2)
CA localized to organ of origin are treated with **local** therapies such as **surgery** vs. **radiation** (2)
197
Chemotherapy is a \_\_\_\_\_(*local vs. systemic*) therapy that is given in what 3 circumstances?
Systemic
1. pt who've had CA removed but still at risk for micrometastasis (return of CA even after removal) = *Adjuvant Chemo*
2. Curative/Palliative tx in **clinically apparent** **metastatic** Dz = *Chemo*
3. Cytoreduction prior to surgery = *N**eoadjuvant Chemo*
198
Describe the 5 Levels of Chemotherapy Tolerance
Pt is...
* 0 = fully active
* 1 = Ambulatory and able to carry out light work but restricted in physically strenuous stuff
* 2 = Ambulatory (up and about \> 50% of waking hours) but unable to carry out any work activities
* 3 = Limited selfcare, confined to bed/chair \> 50% of waking hours
* 4 = Completely Disabled
* 5 = Dead
199
Our ability to cure CA is based on \_\_\_\_\_
Our ability to cure CA is based on **Chemoresistance**. Combining drugs provides broader coverage of de novo resistant cell lines
200
What are the 5 major rules for Creating Chemotherapy Combination
1. Both drugs should have activity against the CA when given alone
2. No overlapping toxicities (except for NVH and myelosuppression)
3. Different MOA
4. Combine CCS with CC**N**S
5. Opitmal Dose, Optimal schedule with Dose response relationship
201
Adjuvant therapy **post surgery** is indicated in which CA (8)
You'll need several [**T**all & **B**eautiful **CLOMPS**], after this surgery!
## Footnote
**T**esticular CA
**B**reast CA - NODE POSITIVE vs. selective node neg.
**C**olorectal CA - NODE POSITIVE
**L**ung CA
**O**steogenic Sarcoma
**M**elanoma - selected pts
**P**ancreatic CA
**S**tomach CA
202
Define the [**Stage** of CA] and how it's determined (3)
Uniform system that indicates **extent** of Dz at time of Dx. Physical exam/Blood test/Imaging are used to determine the [CA stage]
203
[Staging of CA] is often combined with [TMN Classification]. Describe the [TMN Classification]
T =Tumor description (size, penetration into wall)
M= Metastasis present?
N= Nodes (regional) involved
204
Growth Fraction
[# of cells actually dividing]
\_\_\_\_\_\_\_\_\_\_\_\_\_
Total Cell #
205
Skipper Hypothesis
The ability of chemo to cure CA is inversely proportional to the tumor burden
(INC Tumor Burden = DEC chance of chemo cure)
206
Chemocurable CA never develop \_\_\_\_. Name the Chemocurable CA (4)
Chemocurable CA never develops **Resistance**.
1. Testicular CA
2. Some Lymphomas
3. Some Leukemia
4. Hodgkin's Dz
207
Scheduling of Chemotherapy is based on what 3 things
Dose
Route of Admin
[Length of Tx cycle]
208
[Formula for **A**bsolute **N**eutrophil **C**ount] and why it is important
**ANC**= [Total WBC] x [PMN fraction + fraction of bands]
If **ANC** is \< 500 = neutropenia = pt is at risk for endogenous bacteria
209
Which 2 drugs can be given to Chemotherapy pts ___ hours after admin to shorten duration of neutropenia
Given **24** hours post chemo admin
[Filgrastim QD] and [Peg-Filgrastim q3 week] SubQ injections
210
Platelet counts should be maintained above \_\_\_\_. If not, ___ is given. When does platelet count recover?
Platelet counts should be maintained [**\>10K**]. If not, **platelet transfusion** is given. Platelet count recovers between 21-28 Days
211
[Oprelvekin IL11] Indication
DEC frequnecy of platelet transfusions post chemo.
(SE = Fluid retention & arrhythmia)
212
The Chemotherapeutic effect of MTX can be overcome by
[Leucovorin THF] rescue
