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Fall 2021: Therapeutics III > Therapeutics of Prostate Cancer (Weddle) > Flashcards

Therapeutics of Prostate Cancer (Weddle) Flashcards

1
Q

_________ is a growth signal to the prostate.

A

testosterone

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2
Q

_______ is a key enzyme involved in the biosynthesis of testosterone.

A

CYP17A1

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3
Q

Prostate cancer is more common in ___________, and less common in _________.

A

African Americans; Asians

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4
Q

List the two screening modalities for prostate cancer.

A

digital rectal exam (DRE) and prostate specific antigen (PSA)

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5
Q

What PSA level requires evaluation?

A

> 4 ng/mL

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6
Q

What PSA level is highly suspicious for malignancy?

A

> 10 ng/mL

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7
Q

What PSA velocity is suspicious for malignancy?

A

> 0.75 ng/mL rise per year

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8
Q

What factors can decrease PSA levels?

A

finasteride and dutasteride

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9
Q

What factors can increase PSA levels?

A

ejaculation, prostatic manipulation/biopsy, BPH, prostatitis

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10
Q

When would someone receive a transrectal ultrasound?

A

as a follow-up after abnormal PSA or DRE

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11
Q

How often should men 50+ get screened for prostate cancer if they have a PSA of 2.5 OR higher?

A

annually

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12
Q

How often should men 50+ get screened for prostate cancer if their PSA is < 2.5?

A

every 2 years

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13
Q

At what age should high-risk men be screened for prostate cancer?

A

45 (typically)

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14
Q

What was the PCPT Trial?

A

studied finasteride for prostate cancer prevention

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15
Q

During the PCPT Trial, patients on finasteride that developed prostate cancer had disease with a(n) ___________ Gleason score

A

increased

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16
Q

What is the REDUCE Trial currently evaluating?

A

dutasteride for prostate cancer prevention

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17
Q

True or false: finasteride and dutasteride are approved for prostate cancer prevention.

A

false

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18
Q

What did the SELECT Trial assess?

A

if selenium and vitamin E decrease the incidence of prostate cancer in healthy men

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19
Q

What are some signs and symptoms of advanced prostate cancer?

A
  • alterations in urinary habits
  • impotence
  • lower extremity edema
  • weight loss
  • anemia
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20
Q

The most common site of metastasis for prostate cancer is ______.

A

bone

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21
Q

Most prostate cancers are _____________.

A

adenocarcinomas (99%)

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22
Q

What range of Gleason scores indicates that a tumor is slow-growing and well-differentiated?

A

2-4

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23
Q

What range of Gleason scores indicates that a tumor is aggressive and poorly-differentiated?

A

8-10

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24
Q

What does m1 mean?

A

metastatic

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25
Q

What does m0 mean?

A

non-metastatic (PSA only)

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26
Q

What does HSPC mean?

A

hormone sensitive prostate cancer

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27
Q

What does CRPC mean?

A

castrate resistant prostate cancer

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28
Q

Give 1 advantage and 1 disadvantage of observation for localized prostate cancer.

A
  • advantage: avoids immediate morbidity associated with treatment
  • disadvantage: risk of disease complications such as urinary retention or fractures
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29
Q

Give three advantages of active surveillance of prostate cancer.

A
  • ⅔ of patients eligible for surveillance will avoid therapy
  • avoid possible side effects
  • QOL less affected
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30
Q

Give two disadvantages of active surveillance for localized prostate cancer.

A
  • ⅓ of patients may require treatment
  • periodic follow-up and tests/biopsies may be necessary
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31
Q

Can you radiate localized prostate cancer?

A

reasonable alternative to patients who aren’t surgical candidates

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32
Q

What is the definitive, curative therapy for localized prostate cancer?

A

radical prostatectomy + PLND

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33
Q

Due to its perioperative morbidity, radical prostatectomy + PLND should really only be used in men with ______ years life expectancy.

A

> 10 years

34
Q

What is the goal level of testosterone after 1 month of ADT?

A

< 50 ng/dL

35
Q

Give 1 surgical and 1 medicinal method of ADT.

A

surgical: ochiectomy
medicinal: LHRH agonists

36
Q

List 5 antiandrogen drugs.

A
  1. bicalutamide
  2. nilutamide
  3. flutamide
  4. abiraterone
  5. enzalutamide
37
Q

What is the goal of therapy for metastatic prostate cancer?

A

palliation of disease

38
Q

When would you consider ADT in m0HSPC prostate cancer?

A

if rapid PSA velocity or short PSA doubling time + long life expectancy

39
Q

You can give ADT in m0HSPC prostate cancer if PSA doubling time is _________.

A

< 6 months

40
Q

What are the two major toxicities of anti-androgen therapy?

A

impotence and hot flashes

41
Q

LHRH agonists are just as effective as orchiectomies, with the added bonus of being _________.

A

reversible

42
Q

Give four examples of LHRH agonists that can be used for metastatic prostate cancer.

A

leuprolide, goserelin, triptorelin, histerelin

43
Q

Which LHRH agonist is administered as a SQ implant?

A

histerelin

44
Q

Give some acute toxicities associated with LHRH agonists.

A

tumor flare, gynecomastia, hot flashes, ED, edema, injection site reaction

45
Q

Give some long-term toxicities associated with LHRH agonists.

A

osteoporosis, fracture, obesity, insulin resistance, lipid changes, increased risk of diabetic and cardiovascular events

46
Q

What four levels will increase with long-term LHRH use?

A

fat mass, plasma insulin, cholesterol, TGs

47
Q

Choice of LHRH agonist should be based on ________ and ______.

A

convenience; cost

48
Q

How can we present disease flare with LHRH agonist use?

A

add an additional anti-androgen therapy short-term (7 days)

49
Q

What agents make up combined androgen blockade (CAB)?

A

LHRH agonist + anti-androgen

50
Q

True or false: CAB therapy offers maximal benefit over monotherapy.

A

false

51
Q

When can you discontinue androgen suppression during m0HSPC?

A

When PSA returns to a pre-specified baseline

52
Q

What are the two major benefits of intermittent ADT for m0HSPC prostate cancer?

A

decreased cost and decreased side effects

53
Q

What would be a benefit of using an LHRH antagonist over an LHRH agonist?

A

faster drop in testosterone

54
Q

Give an example of an LHRH antagonist that can be used in prostate cancer (not seen often though due to price)

A

degarelix

55
Q

Utilizing an LHRH antagonist eliminates tumor flare and ultimately eliminates the need for ______.

A

ADT

56
Q

What regimen would you recommend for m0CRPC prostate cancer?

A
  • continue ADT (usually an LHRH agonist)
  • add in either enzaluatmide, apalutamide, or darolutamide
57
Q

True or false: abiraterone does not have an indication in the M0 setting.

A

true

58
Q

Enzalutamide decreases serum concentrations of ________.

A

warfarin

59
Q

Use enzalutamide with caution in patients with a history of ________.

A

seizures

60
Q

Enzalutamide should NOT be given with ________.

A

prednisone

61
Q

In what patient groups should you use apalutamide cautiously?

A

history of seizures, QT prolongation, falls, thyroid dysfunction

62
Q

Which anti-androgen drug has 2 phaermacologically active diastereomers?

A

darolutamide

63
Q

Darolutamide may be considered better than other agents in its class due to what?

A

less toxicities

64
Q

At which prostate cancer stage does a patient now have visceral metastases?

A

m1HSPC

65
Q

We will determine therapy for m1HSPC based on the _______ of the disease.

A

volume

66
Q

If not previously performed, what tests should be run for m1HSPC prostate cancer?

A

MSI-H/dMMR and germline testing for gene mutations

67
Q

What drug regimen would you recommend for low volume m1HSPC?

A
  1. ADT (LHRH agonists)
  2. continue ADT and add either: abiraterone + prednisole, enzalutamide, or apalutamide
68
Q

Abiraterone selectively and irreversibly inhibits ________.

A

CYP17

69
Q

What is the 1st line treatment for high volume m1HSPC?

A

docetaxel + ADT

70
Q

In metastatic CRPC, all patients will eventually become _________.

A

hormone refractory

71
Q

In addition to continuting ADT therapy, what other options could be considered for m1CRPC?

A
  • docetaxel (chemo of choice)
  • sipuleucel-T (only for asymptomatic without liver mets)
  • cabazitaxel
  • radium-223
  • abiraterone + prednisone
  • enzalutamide
  • mitoxantrone
  • genomic testing
72
Q

Can sipuleucel T be used for patients with an ECOG score of 2+?

A

no

73
Q

How does cabazitaxel differ from other taxanes?

A

poor affinity for MDR proteins, therefore conferring activity in resistant tumors

74
Q

What regimen is approved 1st line for m1CRPC?

A

docetaxel + prednisone

75
Q

What regimen is approved 2nd line for m1CRPC?

A

cabazitaxel + prednisone

76
Q

Give some toxicities of radium-223.

A

anemia, neutropenia, thrombocytopenia

77
Q

True or false: radium-223 can be used concurrently with chemotherapy.

A

false (due to toxicities)

78
Q

What toxicity is associated with strontium?

A

myelosuppression

79
Q

Can PARP inhibitors be used for prostate cancer?

A

yes; breakthrough therapy designation

80
Q

What drug can be used for prostate cancer that has dMMR/MSI-H characteristics?

A

pembrolizumab

Fall 2021: Therapeutics III (25 decks)

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