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Pharm III - Exam 3 > Oncology > Flashcards

Oncology Flashcards

1
Q

Describe log cell kill kinetics

A
  1. A given treatment kills a constant fraction of cells
  2. Subsequent doses reduce cancer burden proportionally over time
  3. More cells killed, higher chance for cure
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2
Q

Describe Gompertzian model of tumor cell growth

A

Growth fraction of a tumor is NOT constant
-As tumor gets larger, growth fraction decreases
-This results in lower number of cells susceptible to chemo
(so treat earlier!)

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3
Q

What are the principles of combining chemo drugs?

A
  1. Efficacy: each drug must have some anticancer activity on its own
  2. Toxicity: minimize overlapping toxicities
  3. Optimum scheduling: give each drug in intervals to maximize its activity
  4. MOA: multiple to help overwhelm cells’ ability to develop resistance
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4
Q

Describe first line local primary therapy

A

Used in advanced cancer cases in which systemic treatments would NOT be effective

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5
Q

Describe neoadjuvant chemo

A

Used PRIOR to local therapies to improve their effect by reducing size of the tumor

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6
Q

Describe adjuvant chemo

A

Used AFTER local therapies to improve their long term effect by eliminating any remaining undetected cancer cells

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7
Q

Describe dose density of chemo

A
  • Give repeated doses of multiple agents over a period of time
  • Regular exposure provides a wave-like approach to killing cancer cells over time
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8
Q

Define cure in relation to cancer

A
  • Sustained cancer-free period

- Usually 5 years

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9
Q

Define control of cancer

A
  • Reduce cancer burden
  • Prevent extension of cancer
  • Extend survival
  • Cure unlikely
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10
Q

Define palliation

A
  • Reduce symptoms of disease
  • Improve QOL
  • Prolong survival
  • Cure not likely
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11
Q

Define remission/complete response (CR)

A

Unable to detect presence of cancer

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12
Q

Define partial response

A

Reduction in tumor burden but cancer still present

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13
Q

Define treatment failure/progressive disease

A

Cancer continues to grow despite treatment

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14
Q

How can chemo resistance develop?

A
  • Mutations within cancer cells could block chemo actions/uptake, transport drug back out
  • Drug interactions could decrease exposure to chemo within the body
  • Calculated doses could not match pts individual body characteristics
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15
Q

What are the options if primary cancer treatment is unsuccessful?

A
  • Salvage treatment (use other combos)
  • SCT
  • Investigational therapies
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16
Q

Define autologous SCT

A

High dose chemo followed by re-infusion of pt’s own stem cells

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17
Q

Define allogeneic SCT

A

Chemo and immune modulation plus infusion of DONOR stem cells

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18
Q

What are the cell cycle non-specific chemo agents?

A

CAP’N

  • Cytotoxic abx
  • Alkylating agents
  • Platinum compounds
  • Natural products
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19
Q

MOA alkylating agents

A
  • Disrupts normal DNA structure
  • Prevents use of DNA as blueprint for cell division
  • Cell cycle NON-specific
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20
Q

Examples of alkylating agents

A
  • Melphalan
  • Procarbazine
  • Cyclophosphamide
  • Carmustine
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21
Q

Indications for cyclophosphamide

A

Breast cancer, leukemia, lymphoma, myeloma, etc. etc.

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22
Q

Indications for melphalan

A

Myeloma

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23
Q

Indications for procarbazine

A

Lymphoma

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24
Q

Alkylating agents ADEs

A
  • BM toxicity (myelosuppression)
  • Mucositis
  • Sterility (usually temporary)
  • NV
  • Tissue damage (following extravasation)
  • Risk of secondary malignancies
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25
MOA platinum analogs
Unclear - Likely act similar to alkylating agents by binding DNA and forming crosslinks - Also bind to cytoplasmic and nuclear proteins required for cell function
26
Examples of platinum analogs
- Cisplatin - Carboplatin - Oxaliplatin
27
Indications for cisplatin and carboplatin
``` BELHOT Bladder Esophagus Lung Head and neck Ovary Testicular ```
28
Indications for oxaliplatin
PEC Pancreatic Esophageal Colorectal
29
Cisplatin ADEs
- Renal (increase ser Cr, K/Mg wasting) - Anemia - NV - Ototoxicity
30
Carboplatin ADEs
Avoids the major toxicities a/w cisplatin BUT causes myelosuppresison
31
Oxaliplatin ADEs
- Neurotoxicity (peripheral neuropathy) - Myelosuppression - Diarrhea
32
What are antimetabolites?
- Molecules (natural or artificial) that sub for actual components of metabolic processes - Inhibits normal cell processes that produce components of DNA - S phase specific
33
Examples of antimetabolites
- MTX - Capecitabine - Cytarabine - Gemcitabine - Fludarabine - 5-FU - 6-MP
34
MTX MOA
- Antimetabolite - Inhibits DHFR which converts one form of folic acid to another - Inhibits TS
35
Capecitabine MOA
- Antimetabolite - Inhibits TS - Blocks incorporation of FUTP into RNA and dFUTP into DNA (blocking formation of RNA/DNA)
36
5-FU MOA
- Antimetabolite - Same MOA of capecitabine - Inhibits TS - Blocks incorporation of FUTP into RNA and dFUTP into DNA (blocking formation of RNA/DNA)
37
Cytarabine MOA
- Antimetabolite - Mimics cytidine - Inhibits DNA pol and DNA repair that prevents DNA chain elongation
38
Gemcitabine MOA
- Antimetabolite - Inhibits ribonucleotide reductase - Prevents production of deoxytriphosphates for DNA synthesis - Inhibits DNA pol which blocks DNA synthesis and repair
39
Fludarabine MOA
- Antimetabolite | - Same as gemcitabine
40
6-MP MOA
- Antimetabolite | - Inhibits multiple enzymes that synthesize purine nucleotides
41
Indications for MTX
- Leukemia - Lymphoma - Breast cancer - RA
42
Indications for pemetrexed
Lung cancer | antimetabolite
43
Indications for capecitabine
Breast cancer
44
Indications for 5-FU
-Breast cancer -Esophageal -Colorectal etc etc
45
Indications for cytarabine
Leukemia and lymphoma
46
Indications for gemcitabine
``` Pancreas Bladder Breast Lung Ovarian cancers ```
47
What is leucovorin? What does it do?
- Special antimetabolite: NO anticancer action - Reduced form of folic acid - Mimics action of tetrahydrofolate
48
Key uses of leucovorin
1. Reduces MTX toxicity by rescuing normal cells | 2. Increases 5-FU activity against colon cancer
49
MTX ADEs
- Mucositis - Diarrhea - Myelosuppression
50
Capecitabine ADEs
- Palmar plantar erythrodysesthesia (hand-foot syndrome) - Diarrhea - NV - Myelosuppression
51
Which antimetabolites may cause hand-foot syndrome?
Capecitabine | Pemetrexed
52
How is hand-foot syndrome prevented/treated?
Dexamethasone
53
5-FU ADEs
- Mucositis - Diarrhea - Myelosuppression
54
Cytarabine ADEs
- Acral erythema - Cerebellar toxicity - Pulm toxicity - NV - Myelosuppression
55
Gemcitabine ADEs
- Diarrhea - NV - Myelosuppression
56
Pemetrexed ADEs
- Hand foot syndrome - Mucositis - Diarrhea - Rash - Myelosuppression
57
How are ADEs of pemetrexed reduced?
B12 and folic acid supplements
58
Chemo classes derived from natural products
1. Vinca alkaloids (periwinkle plant) 2. Taxanes (yew trees) 3. Epipodophyllotoxins (mayapple root) 4. Camptothecins (Camptothecin acuminata tree)
59
Vinca alkaloids MOA
- Inhibit tubulin polymerization required for microtubule assembly - Results in blocked cell division and causes cell death
60
Indications for vincristine
- Leukemia - Lymphoma - Neuroblastoma - Wilm's tumor - Rhabdomyosarcoma
61
Indications for vinblastine
- Leukemia - Lymphoma - Kaposi's sarcoma - Germ cell cancer
62
Indications for vinorelbine
- Lung - Breast - Ovarian cancer
63
Vinca alkaloids ADEs
- Alopecia - Neuro (peripheral neuropathy) - Constipation - Myelosuppression - Potent vesicant action upon extravasation
64
Taxanes MOA
- Promote microtubule formation | - Prevent disassembly of microtubules, blocking completion of cell division and leads to cell death
65
Examples of taxane agents
- Paclitaxel - Docetaxel - Cabazitaxel - Ixabepilone
66
Indications for paclitaxel
- Ovary - Lung - Prostate - Breast - Head and neck - Esophageal - Bladder
67
Indications for docetaxel
- Breast - Lung - Head and neck - Gastric - Ovary - Bladder
68
Indications for cabazitaxel
Prostate cancer
69
Indications for ixabepilone
Breast cancer
70
Taxanes ADEs
- Myelosuppression - Hypersensitivity reactions - Peripheral neuropathy - Fluid retention (docetaxel)
71
Which taxane causes fluid retention?
Docetaxel
72
Epipodophyllotoxins MOA
- Inhibit DNA topoisomerase II | - Prevents proper unwinding of DNA resulting in blockade of DNA synth and cell division
73
Examples of epipodophyllotoxins
Etoposide | Teniposide
74
Indications for etoposide
- Lung - Germ cell - Lymphoma - Gastric cancer
75
Indications for teniposide
Pediatric leukemia
76
Epipodophyllotoxins ADEs
HAM - Hypotension (if infused too quickly) - Alopecia - Myelosuppression
77
What are antitumor antibiotics?
- Derived from bacteria to compete for resources | - Anthracyclines (doxorubicin, daunorubicin, bleomycin, etc.)
78
Anthracyclines MOA
- Inhibit topoisomerase 2 - Bind to DNA and intercalate strands - Generate free radicals - Bind to cell membranes and alter fluid/ion transport
79
Indications for doxorubicin
- Breast cancer - Myeloma - Leukemia - Lymphoma
80
Indications for daunorubicin and idarubicin
Leukemia
81
Indications for epirubicin
- Breast | - Gastroesopageal
82
Indications for mitoxantrone
- Leukemia - Lymphoma - Prostate - MS
83
Which anthracycline can be used in MS?
Mitoxantrone
84
Anthracyclines ADEs
- Mucositis - Alopecia - Myelosuppression - NV - Vesicant if extravasated - Cardiotoxicity
85
ADE of mitoxantrone
Turns urine blue/blue-green
86
ADE of doxo/dauno/ida/epirubicin
Turns urine reddish-orange
87
Which anthracyclines turn urine blue or blue-green?
Mitoxantrone
88
Which anthracyclines turn urine reddish-orange?
Doxorubicin Idarubicin Epirubicin Daunorubicin
89
Describe cardiotoxicity of anthracyclines
- Acute: within 24-72 hrs, usually subclincial, arrhythmias/pericarditis/myocarditis - Chronic: dose dependent, delayed by years, results in cardiomyopathy and associated heart failure
90
What dose can cardiotoxicity of anthracyclines occur?
Any dose, but risk increases with cumulative dosing
91
What is dexrazoxane used for?
- To mitigate cardiotoxicity of anthracyclines - Reduces free radical formation in cardiac tissue * May reduce therapeutic effect of doxorubicin though
92
What is a major concern of bleomycin use?
Pulmonary toxicity
93
Risk factors for pulm toxicity with bleomycin use?
- Age over 70 - Cumulative doses over 400 units - Underlying pulm disease - Prior mediastinal radiation - Supplemental oxygen
94
What is bleomycin used for?
- Lymphoma - Germ cell - Head and neck - Squamous cell cancers - Sclerosing agent for pleural effusions
95
What are tyrosine kinases?
- Families of proteins that use ATP to phosphorylate other proteins - Often over active in cancer cells leading to enhanced tumor growth
96
TKI MOA
- Block tyrosine kinases - Results in inhibiting specific regulatory pathways - Promotes cancer cell death
97
How can resistance to TKIs develop?
Mutations in AA sequence of the specific tyrosine kinase could prevent a TKI from binding the targeted site
98
Which TKIs are indicated for Ph+ CML and ALL?
- Bosutinib - Imatinib - Nilotinib - Dasatinib - Ponatinib (off market)
99
Indications for erlotinib
Lung and pancreatic cancer
100
Which TKIs are indicated for renal cell cancer?
Sorafenib and sunitinib
101
Indications for lapatinib
Breast cancer
102
Indications for crizotinib
Lung cancer
103
Indications for gefinitib
Lung cancer | off market now
104
TKI ADEs
- Rash - Myelosuppression - Fatigue - Fluid retention - Diarrhea - Myalgia - CHF
105
Drug interactions with TKIs
CYP450 - Inhibitors (like azoles) can decrease metabolism - Inducers (like phenytoin) can increase metabolism - Reduced availability with PPIs and H2 blockers
106
Immunomodulators MOA
Unclear - May alter TNF levels - May increase NK cells, IL2, interferon activity - May promote apoptosis
107
What are immunomodulators MC used to treat?
Myeloma | usually combined with dexamethasone
108
Examples of immunomodulators
Thalidomide Lenalidomide Pomalidomide
109
Immunomodulators ADEs
- Peripheral neuropathy - Thromboembolism - Fatigue - Rash - Myelosuppression - Dizzy/drowsy
110
Proteasome inhibitor MOA
- Inhibit complexes of proteins that would otherwise break down unneeded or damaged proteins - Promote activation of apoptosis pathways
111
Indications for proteasome inhibitors
Myeloma
112
Examples of proteasome inhibitors
Bortezomib | Carfilzomib
113
Proteasome inhibitor ADEs
- Activation of herpes zoster/simplex - Pulm toxicity - Diarrhea, NV - Myelosuppression - Neuralgia - Peripheral neuropathy - Heart failure
114
How to identify monoclonal antibodies
- Prefix: company specific - Target: tu is tumor, ci is circulatory system - Source: zu is humanized, xi is humanized/chimeric, mu is mouse - Suffix: mab
115
How mAb kill tumor cells?
Not always clear, could be multiple mechanisms - Block receptors - Bind free protein ligands looking to bind receptors - Bind to receptors and trigger apoptosis or ADCC
116
Indications for rituximab
CD20 positive lymphoma
117
Indications for trastuzumab
HER2/neu overexpressing breast cancer
118
Indications for cetuximab
- Lung - Head and neck - Colorectal cancer
119
Indications for panitumumab
Colorectal cancer
120
Indications for bevacizumab
- Colorectal - Breast - Lung - Renal cell cancers
121
mAb ADEs
Infusion related reactions (give premeds - acetaminophen, diphenhydramine plus or minus dexamethasone)
122
How to avoid infusion reactions with mAbs?
Give premeds (acetaminophen, diphenhydramine plus or minus dexamethasone)
123
Bevacizumab ADEs
- GI perforation - Arterial thromboembolic events - Delayed wound healing
124
Trastuzumab ADEs
Heart failure
125
Panitumumab and cetuximab ADEs
- Hypomagnesemia | - Interstitial lung disease
126
What is asparaginase and how does it work?
- Enzyme antineoplastic agent | - Breaks down aspargine to aspartate (deprives tumor cells of necessary AA and leads to apoptosis)
127
MC used form of asparaginase?
E coli asparaginase
128
Forms of asparaginase
- E coli asparaginase - PEG-aspargase (long acting) - Erwinia asparaginase (for pts who have hypersensitivity reaction to E coli form)
129
Indications for asparaginase
Part of combo chemo to treat ALL
130
Asparaginase ADEs
- Hypersensitivity - Clotting and bleeding d/os - Pancreatitis - Neuro toxicity
131
Goal of phase I clinical trials
Assess safety (10-20 pts)
132
Goal of phase II clinical trials
Assess efficacy (20-40 pts)
133
Goal of phase III clinical trials
Assess efficacy compared to standard treatment (lots of patients, randomized)
134
Describe ALL
- Children - Induction, consolidation, maintenance therapy - Combo treatment over 2-3 yrs - Requires intrathecal chemo d/t chance for spread to CNS - Good chance for cure
135
Quick hits: AML
- Adults - Induction and consolidation treatment - 7 plus 3 regimen (cytarabine, daunorubicin) - Some pts considered for ASCT
136
Quick hits: CML
- Philly chromosome - Chronic, accelerated, blast stages - Use TKIs to control disease - ASCT only known cure
137
Quick hits: CLL
- Elderly - Treat when symptomatic - Many options and aimed at controlling symptoms, prolonging survival - Little chance for cure
138
Quick hits: Hodgkin's lymphoma
- Reed-Sternberg cells - EBV related - Classic B symptoms (fever, night sweats, wt loss) - Lymphadenopathy - Several months of chemo plus or minus XRT - ABVD regimen
139
Quick hits: NHL
- B symptoms and lymphadenopathy - NO RS cells like HL - CHOP or R-CHOP (if CD20 positive)
140
Quick hits: myeloma
- Malignant plasma cells produce abnormal IGs - Only stages 2 and 3 receive treatment - Requires pain and anemia management - Bisphosphonates to control bone lesions
141
Quick hits: breast cancer
- Both men and women - Screening is key - Treatment based on stage and pre/postmeno status - Cure possible in all but stage IV disease
142
Quick hits: prostate cancer
- Elderly men - Treatment not always provided - Treatment types: hormonal, chemo, brachytherapy, surgical - Monitor PSA and androgen levels for response to treatment
143
MC GI cancer?
Colorectal
144
Quick hits: colorectal cancer
- MC GI cancer | - Common chemo regimens: FOLXFOX, FOLFIRI
145
FOLFOX and FOLFIRI are common chemo regimens for which cancer?
Colorectal
146
Quick hits: ovarian cancer
- Typically slow growing and difficult to detect until later stages - Chemo options: paclitaxel with cisplatin/carboplatin, topotecan, altretamine, liposomal doxorubicin
147
Quick hits: testicular cancer
- Younger population 20s-40s | - Combo chemo: BEP (bleomycin, etoposide, cisplatin), ICE (ifosfamide, cisplatin, etoposide)
148
Quick hits: malignant melanoma
- Curable in early stages w/surgery - Mets is relatively drug-resistant - Chemo aims to prolong survival (dacarbazine, temozolomide, cisplatin, aldesleukin)
149
Quick hits: brain cancer
- Multiple types | - Require chemo to be able to cross BBB (carmustine, lomustine, temozolomide)
150
Which chemos can cross BBB?
Carmustine Lomustine Temozolomide
151
Quick hits: secondary malignancies
- Caused by previous XRT/chemo - MC acute leukemia or lymphoma - More difficult to treat - MC a/w alkylating agents and etoposide
152
What is the MC type of secondary cancer?
Usually acute leukemia or lymphoma
153
What agents are MC a/w development of secondary cancers?
Alkylating agents and etoposide
154
Define vesicant
Blistering agent - severe skin, eye, mucosal pain and irritation
155
Define extravasation
- Administration of IV infusions into the extravascular space/tissue around infusion sites - Can cause severe damage
156
Which chemotherapies are potent vesicants upon extravasation?
- Anthracyclines | - Vinca alkaloids
157
Which chemo may cause pulmonary toxicity?
Bleomycin
158
Which chemo may cause thromboembolism?
Thalidomide (immunomodulator)
159
Which chemo may cause cardiotoxicity?
Doxorubicin (anthracycline)
160
Which chemo may cause myelosuppression?
Carboplatin
161
Which chemo may cause nephrotoxicity?
Cisplatin
162
Which chemo may cause hypersensitivity reaction?
Asparaginase
163
Which chemo may cause delayed wound healing?
Bevacizumab
164
Which chemo may cause cerebellar toxicity?
Cytarabine (antimetabolite)
165
Which chemo may cause neurotoxicity?
Vincristine (vinca alkaloid)
166
Ways to avoid cardiotoxicity with anthracyclines?
1. Limit lifetime doses | 2. Use dexrazoxane
167
What does the Philadelphia chromosome create?
BCR-ABL (over active tyrosine kinase)
168
What are hormone sensitive cancers?
1. Breast | 2. Prostate
169
What is imatinib MC used to treat?
CML
170
What is thalidomide MC used to treat?
Myeloma
171
What is asparaginase MC used to treat?
ALL
172
What would 5-FU with leucovorin be used to treat?
Colon
173
What would trastuzumab be used to treat?
Breast
174
What would goserelin be used to treat?
Hormonal for prostate (androgen dependent) cancer

Pharm III - Exam 3 (2 decks)

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