Exam 2 Oncology Flashcards
Anticipatory Nausea/Vomiting
- learned response conditioned by severity and duration of previous emetic reactions from prior cycles of chemo
- can be provoked by sight, sound, or smell
Acute Nausea/Vomiting
- usually within 24 hours of receiving chemo
Delayed Nausea/Vomiting
- occurs > 24 hours following completion of chemo
- NK-1 receptor and substance P binding
Breakthrough Nausea/Vomiting
- occurs even if on scheduled anti-emetics prior to chemo
Refractory
- nausea/vomiting that persists despite appropriate anti-emetics
- failed other therapies
Receptor involved in Nausea/Vomiting
chemoreceptor trigger zone (CTZ)
Nausea
the inclination to vomit or as a feeling in the throat or epigastric region alerting an individual that vomiting is imminent
Wretching
the labored movement of abdominal and thoracic muscles before vomiting
Vomiting
the ejection or forced expulsion of gastric contents through the mouth
Highly Emetogenic Chemotherapy
- > 90% Frequency of Emesis
- Level 5
- cisplatin
Moderately Emetogenic Chemotherapy
- > 30 - 90% frequency of emesis
- level 3-4
Low Emetic Risk
- 10-30% frequency of emesis
- level 2
Minimial Emetic Risk
- < 10% frequency of emesis
- level 1
Combination Chemotherapy Emetogenic Risk
- level 1 and 2 agents do not contribute to the emetogenicity of the regiment
- adding level 3-4 agents increases the emetogenicity of the combination regimen by 1 level per agent
Risk Factors for CINV
- women > men
- younger patients > older patients
- prior history of motion sickness
- previous CINV tend to do worse
- anxiety/high pretreatment anticipation of nausea
- chronic ethanol can be protective
Prophylaxis for acute N/V is based on what?
emetogenic potential of chemotherapy
Highly Emetogenic: Regimen A
- NK-1 antagonist ( -pitant)
- Dexamethasone
- 5-HT3 antagonist (-setron)
- Olanzapine
Highly Emetogenic: Regimen B
- Olanzapine
- Palonosetron
- Dexamethasone
- +/- lorazepam 0.5 mg-2mg po or iv or sublingual every 4-6 hours PRN
- +/- H2 blocker or PPI
Highly Emetogenic: Regimen C
- NK-1 antagonist
- steroid
- 5-HT3 antagonist
- +/- lorazepam 0.5 mg-2mg po or iv or sublingual every 4-6 hours PRN
- +/- H2 blocker or PPI
Moderately Emetogenic: Regimen A
- Dexamethasone
- 5HT3 antagonist
- +/- lorazepam 0.5 mg-2mg po or iv or sublingual every 4-6 hours PRN
- +/- H2 blocker or PPI
Moderately Emetogenic: Regimen B
- Olanzapine
- Palonosetron
- Dexamethasone
- +/- lorazepam 0.5 mg-2mg po or iv or sublingual every 4-6 hours PRN
- +/- H2 blocker or PPI
Moderately Emetogenic: Regimen C
- NK-1 Antagonist
- Dexamethasone
- 5-HT3 Antagonist
- +/- lorazepam 0.5 mg-2mg po or iv or sublingual every 4-6 hours PRN
- +/- H2 blocker or PPPI
Low Emetogenic Regimens
- PICK ONE
- Dexamethasone
- Metoclopramide +/- diphenhydramine
- Prochlorperazine
- 5-HT3 Antagonist
- +/- lorazepam 0.5 mg-2mg po or iv or sublingual every 4-6 hours PRN
- +/- H2 blocker or PPPI
Breakthrough Nausea and Vomiting Treatment
- PICK ONE
- Haloperidol
- Metoclopramide +/- diphenhydramine
- prochlorperazine
- promethazine
- olanzapine
- benzodiazepines
- cannabinoids
- 5-HT3 antagonist
- dexamethasone
- scopolamine
Delayed Nausea/Vomiting Treatment
- One of the following
- Dexamethasone
- NK-1 antagonist
- olanzapine
Anticipatory Nausea and Vomiting Treatment
- optimal antiemetic therapy during every cycle of treatment
- behavioral
- acupuncture/acupressure
- lorazepam
Oral Chemo High to Moderate Emetogenic Risk
- start before chemo and continue daily
- 5-HT3 antagonists
Oral Chemo Low to Minimal Emetogenic Risk
- start before chemo and maybe given daily or as needed
- metoclopramide
- 5-HT3 antagonists
Total Body Irradiation Emesis Pretreatment
- start for each day of radiation
- granisetron PO +/- dex
- ondansetron PO +/- dex
Common Toxicities: 5-HT3 Antagonists
- headache (not class effect)
- asymptomatic and transient EKG changes at max doses
- constipation
- increased transaminases
Common Toxicities: Corticosteroids
- anxiety
- euphoria
- insomnia
- hyperglycemia
- increased appetite
Common Toxicities: Substance P Antagonists
- hiccups
- worry about drug interactions
Common Toxicities: Dopamine Antagonists (chlorpromazine, haloperidol, metoclopramide)
- EPS
- diarrhea
- sedation
Common Toxicities: Olanzapine
- dystonic reactions
- sedation
Common Toxicities: Phenothiazines (prochlorperazine, promethazine)
- sedation
- akathesia
- dystonia
- IV promethazine = tissue damage
Common Toxicities: Cannibanoids
- drowsiness
- dizziness
- euphoria
- mood changes
- hallucinations
- increased appetite
Common Toxicities: Benzos
- sedation
- hypotension
- urinary incontinence
- hallucinations
Common Toxicities: Scopolamine
- anticholinergic side effects
When are anti-emetics most effective?
- prophylaxis
- 5-30 minutes prior to chemo and around-the-clock until chemo is complete
- provide PRN agents for breakthrough
Mucositis Progression
- paralleles the neutrophil nadir and begins on day 5 to 7 after chemotherapy and improves as the neutrophil count increases
Mucositis: continuous infusions __ short IV infusions
>
Risk factors for mucositis?
- pre-existing oral lesions
- poor dental hygiene or ill-fitting dentures
- patients receiving both chemo and radiation
Mucositis: Diet Recommendations
- avoid rough food, spices, salt, acidic fruit
- mainly eat soft or liquid foods, nonacidic fruits, soft cheeses, and eggs
- avoid smoking and alcohol
Mucositis: Pretreatment
- baking soda rinses BID-QID
- soft bristled toothbrush to minimize gingival irritation
- saliva sub for radiation induced xerostomia
Mucositis: Oral Cryotherapy
- vasoconstriction may decrease chemotherapy delivery to the oropharyngeaal mucosa
- use of ice chips 30 minutes prior to 5-FU doses has been shown to decrease mucositis incidence
Mucositis: Sucralfate
- forms protective barrier
- swish and swallow (1 gm PO QID) has been shown in some trials to significantly decrease pain
- some patients find the taste and texture of sucralfate to be nauseating; not good data to support use
Mucositis: Oral and PR Opioids
- moderate to severe mucositis
- many oral solutions contain a high percentage of alcohol, which may burn
- best administered around the clock
- PCA is common
Neutropenia: WBCs
- < 0.5 x 10^3/uL
- risk of life-threatening infections
Neutropenia: Platelets
- thrombocytopenia = < 100 x10^3/uL
- risk of bleeding increases when platelet count is ≤ 20 x 10^3/uL and therefore may require transfusion
Neutropenia: RBCs
- anemia
- risk of hypoxia and fatigue
- Hgb z, 11 g/dL or >2g/dL drop from baseline should undergo work-up
What is the most common dose-limiting toxicity of chemo?
bone marrow suppression
What is the nadir?
- the absolute neutrophil count or ANC
- the lowest value the blood counts fall to during a cycle of chemotherapy
- occurs 10-14 days after chemo administration
- counts usually recover by 3 to 4 weeks after chemo
Guidelines to administer chemo safely in patient’s with neutropenia
- WBC > 3000 OR
- ANC of >1500 AND
- Platelet count ≥ 100 x 10^3/uL
Severe Neutropenia
- ANC < 0.5 x 10^3/uL
Febrile Neutropenia Definition
- ANC < 0.5 x 10^3/uL AND
- single oral temp > 101ºF or ≥ 100.4ºF for at least an hour
- other signs/symptoms of infection are absent with fever being the only reliable indicator
Prophylactic Use of CSFs
decreased
- incidence of febrile neutropenia
- LOS
- confirmed infections
- Duration of antibiotics
When to administer primary CSF prophylaxis?
- if the patient is to receive a chemo regiment that is expected to cause ≥ 20% incidence of febrile neutropenia
High Risk Patients of FN
- preexisting neutropenia due to disease
- extensive prior chemo
- previous irradation to the pelvis or other areas containing large amounts of bone marrow
Secondary Prophylaxis using CSF
- patient experienced a neutropenic complication from a previous cycle of chemo and you want to prevent that again
- use a CSF preventatively with the next cycle of chemo
Other Uses for CSFs
- support patients through dose dense chemo
- can be used alone, after chemo, or in combination with plerixafor to mobilize peripheral blood progenitor cells
- after a stem cell transplant to reduce the duration of severe neutropenia
- guidelines for pediatric use are available and should be followed
Filgrastim (Neupogen) G-CSF and Sargramostim (Leukine) GM-CSF
- dose dependent elevation in ANCE
- rapid drop in WBC and neutrophil count following discontinuation
Pegfilgrastim (Neulasta)
- non-linear PK
- clearance increases with increasing neutrophil count
- longer half life
- much more expensive
Filgrastim: Dosing
- start up to 3-4 days after completion of chemo and continue until post-nadir ANC recovery to normal or near normal levels
- 5 mcg/kg/day
- come in 300 and 480 mcg single use vials (round dose to the nearest vial size)
Pegfilgrastim: Dosing
- start at least 24 hours after chemo and can be given up to 3-4 days after chemo (same day administration is not recommended)
- 6 mg SQ x 1 dose
GSF Adverse Effects
- flu like symptoms
- bone and joint pain due to rapid proliferation of the bone myeloid cells
- DVT
- splenic enlargement with long term CSF use
General Causes of Anemia
- decreased RBC production
- decreased erythropoietin production (renal dysfunction)
- decreased body stores of b12, iron, folic acid
- blood loss
Significance of Anemia in Cancer
- fatigue
- low hemoglobin correlated with poor performance status –> decreased survival
- decreased quality of life
Treatment of Chemo Induced Anemia
- if the patient is symptomatic
- tranfuse as indicated
- consider ESA (not indicated for patients receiving myelosuppressive chemo when anticipated outcome is cure)
- iron studies
ESAs are not recommended when:
- curative intent
- patients not receiving chemo
- patients receiving non-myelosuppressive chemo
Epoeitin Alpha Clinical Pearls
- if the Hgb increases > 1 g/dL in a 2-week period, the dose should be decreased by 25% for epoetin alpha and 40% for darbepoeitin
- Starting dose: TID SQ
- maintenence: Weekly SQ
Darbepoetin Clinical Pearls
- Starting Dose: weekly
- Maintenence: every 3 weeks
Iron in Anemic Cancer Patients
- all oncology patients who are prescribed ESA therapy should have baseline iron studies performed
- serum ferritin, iron, iron sat
- Iron Dextran, Iron Sucrose, Ferric Gluconate
Chemos that cause Myalgias/Arthralgias
- Taxanes
- ARs
Treatment for myalgias/arthralgias
- nsaids
- maya require opioids
Chemos that cause hemorrhagic cytitis
- high dose cyclophos
- ifosfamide
Treatment for hemorrhagic cystitis
- hydration (prevention)
- mesna (used to prevent)
Chemos that cause HF
- anthracyclines
- high dose cyclophosphamide
- trastuzumab (other HER2 targeted therapies)
Treatment of HF
- monitor cumulative dose
- assess for risk factors
- dexrazoxane (chemoprotectant)
Chemos that cause peripheral neuropathy
- taxanes
- vinca alkaloids
- platinums
Treatment of Peripheral Neuropathy
- change infusion rate (ie paclitaxel)
- adjunctive pain medications (gabapentin, amitriptyline)
Chemos that cause pulmonary toxicities
- bleomycin
Treatment of pulmonary toxicities
- corticosteroids (no good treatment once it happens)
Mesna
- should be used with standard ifosfamide doses of < 2.5 g/m2/day to decreas risk of hemorrhagic cystitis
Cardiac Toxicity
- formation of iron-dependent oxygen free radicals due to stable AC-iron complexes, which cause catalysis of electron transfer
Type I Chemo Related Cardiac Dysfunction: Acute
- occurs immediately after a single dose or course of therapy with AC
- may involve abnormal ECG findings
- not related to cumulative dose and is uncommon
Type I Chemo Related Cardiac Dysfunction
- onset usually within a year of receiving AC therapy
- rapid onset and progression
- common and life threatening
- related to cumulative dose patient received
Type I Chemo Related Cardiac Dysfunction: Late- onset
- develops several years or even decades after therapy
- manifests as ventricular dysfunction, CHF, conduction disturbances, and arrhythmias
- pediatric cancer survivors who received AC
Which drug causes Type II Chemo Related Cardiac Dysfunction?
Trastuzumab
Type II Chemo Related Cardiac Dysfunction
- appears to be largely reversible and short lived
- lower incidence in non-AC treated patients
- if trastuzumab given with AC, incidence can increase up to 27% cardiac toxicity (NYHA class III/IV)
Assessment of Pain
O: onset
P: provokes
Q: quality
R: radiate
S: severe
T: time
U: understanding
Principles of Pain Management
- understand the cause of pain
- regular administration of around the clock agents combined with PRN agents
- individualized therapy
- necessary to monitor for therapeutic and adverse effects
- use the lowest dose necessary
- pain assessment is subjective
Mild Pain Regimen
- non-opioid ± adjuvent
Moderate Pain Treatment
- opioid for mild-to-moderate pain
- ± non-opioid
- ± adjuvant
Severe Pain
- opioid for moderate-to-severe pain
- ± non-opioid
- ± adjuvant
Common Non-Opioids
- scale 1-3
- APAP
- Advil
- Aspirin
Combo Products/Mild Opioids
- 4-6
- Hydrocodone/APAP
- Oxycodone/APAP
- Hydrocodone/Ibuprofen
- Oxycodone/Ibuprofen
- Tramadol
- Oxycodone/Aspirin
- Condeine/APAP
Opioids
- 7-10
- morphine
- hydromorphone
- methadone
- oxycodone
- fentanyl
- no max dose
Morphine
- metabolized in the liver
- excreted renally and will accumulate in renal insufficiency
Morphine Dosage Forms
- short acting
- long acting
- solutions
- IV
- PR
Hydromorphone
- metabolized in liver
- all renally excreted
- lower dose or longer dosing intervals in renal insufficency
Hydromorphone Dosage Forms
- short acting
- long acting
- solution
- IV
- PR
Oxycodone
- CYP2D6
- over sedation and CNS toxicity in renal failure patients
- use in caution in liver dysfunction
Oxycodone Dosage Forms
- short acting tablets
- long acting tablets
- solutions
- NO IV
Fentanyl
- metabolized in liver
- safe in renal dysfunction
- great for refractory N/V and head/neck/esophageal cancers who may not be able to maintain PO intake
Fentanly: Dosage Forms
- patch
- IV
- buccal
- nasal spray
- lozenges
Fentanyl: REMS
- exposes users to risks of addiction, abuse, misuse, which can lead to overdose
- not good for patients who are opioid naive
- accidently exposure in children can result in fatal overdose
- avoid exposing patch and surrounding area to direct external heat
Methadone: When to Consider
- true morphine allergy
- with opioid induced ADRs
- with pain refractory to other opioids
- with neuropathic pain
- who need long-acting oral dosage form at low cost
Methadone: Avoid
- numerous drug interactions
- risks for syncope or arrhythmias
- history of unpredictable adherance
- poor cognition
Methadone Clearance
- exreted in the urine and feces
- no ADR related to methadone in patients with renal failure
- not advised in severe liver dysfunction
- QT prolongation
Administration of Opioids
- oral is the preferred route
- must consider long-acting and short-acting agents and allow for overlapping effects
Opioids: Constipation
- always add a bowel regimen
- mild stimulant ± stool softener)
Opioids: Sedation
- tolerance typically develops within a few days
- hold sedatives and/or anxiolytics
- consider a dosage reduction
Opioids: N/V
- change opioid
- take with food
- consider addition of scheduled anti-emetic therapy
Opioids: Pruritus
- most seen with morphine administration
- decrease the dose or change opioid
- consider the addition of anti-histamine such as diphenhydramine
Opioids: Hallucinations
- decrease dose or change opioid
- consider neuroleptic medication
Opioids: Confusion/Delirium
- decrease dose or change opioid
- consider neuroleptic medication
Opioids: Myoclonic Jerking
- may be a sign of toxicity
- consider changing opioid or treating underlying cause
Opioids: Respiratory Depression
- give low dose Narcan
- hold opioids
- sedation precedes respiratory depression
PCA
- patient demand ± basal infusion of opioid with lockout interval
- patient must be awake and oriented to self administer their doses (only the patient is to press the button)
- use with caution in patients with sleep apnea
PCA Basal Rate
- can be added once it becomes more clear that the patient requires frequent PCA use over several hours
- use caution with opioid naive patients
Adjusting PCA
- cut or stop basal rate when patient no longer needs it
- if they have received multiple boluses then increase the basal rate
Changing from PCA to Oral
- calculate 24 hour dose
- convert to equi-analgesic 24 hour dose of the new agent using the conversion chart above
- reduce dose by ~25% to account for incomplete cross-tolerance
- divide total 24 hour dose into the appropriate dose
- always add breakthrough PRN dosing, generally 10-20% of total 24 hour oral dose available q4h if oral and more often if IV
Intrathecal Pain Pump
- use in patients who are refractory to other opioid therapy or increased toxicities
- use much smaller doses
- can use baclofen and clonidine
Radiation Therapy Indication
- painful bony metastases, brain metastases, spinal cord compression
Adjuvant Pain Alternatives
- dex
- NSAIDs
- neuropathic pain
- dont treat anxiety/depression with opioids
Breast Cancer: Risk Factors
- age
- family history
- personal history
- Radiation treatment
- estrogen exposure (early menarche or late menopause)
- exogenous estrogen
- alcohol
- prior breast biopsies with proliferative histology
- nulliparity or age > 30 years old before first birth
- elevated body mass and diet
- more than 60% of patients will not have any risk factors
BRCA-1
- Tumor suppressor gene involved in DNA repair
Ductal Carcinoma in Situ
- normal cells have undergone pre-malignant genetic transformation
- typically seen as microcalcifications on a mammogram
Lobular Carcinoma in Situ
- has not invaded beyond the lobule basement membrane
- usually, an incidental finding on biopsy specimen obtained because of symptoms or mammographic findings consistent with benign lesions
Inflammatory Breast Cancer
- aggressive form with rapid onset and poor prognosis
Presentation of Breast Cancer
- > 90% with painless bump on breast
- nipple discharge, retraction, or aching
- asymptomatic disease may be detected on screening mammography
- 50% of patients with an initial diagnosis of breast cancer
Diagnosis of Breast Cancer
- History and PE
- Clinical breast exM
- Mammogram
- breast ultrasound
FISH Testing
- can test for HER2 status
- IHC detects protein expression (1+, 2+, 3+)
- FISH detects gene amp
OncotypeDx
- genetic test for expression of 21 genes which give a recurrence score
- can determine the likelihood that the breast cancer will return and whether the patient is likely to benefit from chemo
Oncotype Dx Scoring: TAILORx
- Low risk (<26) = hormonal therapy only
- high risk (≥26) = chemo and hormonal therapy
RXPonder
- lymph node+ disease
- Low risk (<26) = hormonal therapy only
- high risk (≥26) = chemo and hormonal therapy
- both pre-menopausal and post menopausal patients LN+ disease
Sites of Metastasis in Breast Cancer
- Bone
- Liver
- Lungs
- Brain
- distant lymph nodes
- skin
Neoadjuvant and Adjuvant Therapy: Breast Cancer
- Stage I, IIA, III disease
- cure
- neoadjuvant for patients with larger tumors > 1 cm
Breast Cancer: RS ≤ 15
adjuvant endocrine therapy ± OS
Breast Cancer: RS 16-25
Adjuvant endocrine therapy ± or adjuvant chemo followed by endocrine therapy
Breast Cancer: RS ≥ 26
adjuvant chemo followed by endocrine
Systemic Adjuvant Therapy: HER2 Positive
- Tumor ≤ 0.5 cm: consider adjuvant endocrine therapy ± chemo with HER2 targeted therapy
- Tumor > 0.6 cm: adjuvant chem with HER2 therapy followed by endocrine therapy
Adjuvant Hormonal Therapy: Surgical Ablation
- ooherectomy
- remoes the largest source of estrogen
Adjuvant Hormonal Therapy: SERMS
- tamoxifen
- anti-estrogenic effects in breast but estrogenic properties in other tissues
- major toxicities: hot flashes
Adjuvant Hormonal Therapy: LHRH Analogs
- leuprolide and Goserelin
- initially increases release of FSH and LH
- long term sustained exposure inhibits LH and FSH by inhibits estrogen production by the ovaries
Aromatase Inhibitors
- only in postmenopausal status
- no dvt/ endometrial cancer, not protective on bone
Premenopausal at Diagnosis of Breast Cancer
- Tamoxifen x 5 years ± OS
- AI x 5 years +/- OS
Postmenopausal treatment for a patient who was premenopausal at diagnosis
- could consider an additional 5 years of AI to total 10 years
OR
- consider T x 5 more years to complete 10 years
Premenopausal treatment for a patient who was premenopausal at diagnosis
- T x 5 more years to complete a total of 10 years
OR
- no further endocrine therapy
Adjuvant Hormonal Therapy for a patient who is Postmenopausal at Diagnosis
-AI x 5 years then consider AI for additional 5 more years
OR
T x 2-3 years then followed by AI to complete a total of 5 years or vice versa
OR
T x 4.5-6 years then AI x 5 years or T x 5 more years to complete a total of 10 years
Adjuvant Chemo for HER2 Negative
Dose Dense AC –> Paclitaxel
- Doxorubicin
- Cyclophosphamide
- Paclitaxel
- Filgrastim
OR
TC
- Docetaxel
- Cyclophosphamide
Dose Dense AC: CALBG Trial Group 4
every 2 weeks plus filgrastim = concurrent doxorubicin and cyclophosphamide followed by paclitaxel
Cardiotoxicity in Chemo
- if cardiac problems, can consider docetaxel and cyclophosphamide (TC) chemo regimen to avoid Anthracyclines
What should patients receive as pre-medications with paclitaxel?
- dexamethasone
- diphenhydramine
- H2 antagonist
What does HER2 positive disease greatly benefit from?
The incorporation of HER2 targeted therapies in the regiment such as trastuzumab
What are the preferred adjuvant HER2+ regimens?
APT
- paclitaxel
- trastuzumab
TCH
- docetaxel
- carboplatin
- trastuzumab
TCHP
- docetaxel
- carboplatin
- trastuzumab
- pertuzumab
What is the Triple Negative Breast Cancer standard of care?
Pembrolizumab + Paclitaxel + Carboplatin
Breast Cancer Metastatic Disease Goal
- palliation
- bone and soft tissue metastases tend to have a better prognosis and respond to hormonal therapy
- ER/PR+ tend to be more indolent
- Symptomatic = chemo
ER/PR+, Bone Mets, Asymptomatic Visceral Disease
- Endocrine Therapy +/- bisphosphonate or denosumab
OR
- Clinical Trials
ER/PR-, Symptomatic Visceral Disease or Hormone Refractory, HER2+
- anti-HER2 therapy ± chemo
ER/PR-, Symptomatic Visceral Disease or Hormone Refractory, HER2-
Chemo
When to give hormonal therapy in breast cancer patients?
- ER and/or PR positive disease
- long disease-free survival
- prior response to therapy
- bone only disease
When to give chemotherapy in breast cancer patients?
- ER/PR negative disease
- short disease-free interval
- rapidly progressing disease
- disease refractive to hormonal therapy
If the patient has a shorter disease-free interval with hormonal therapy, what should you do?
- switch to chemo as hormonal therapy is likely not working
Which patients respond better to chemo?
- better performance status
- less extensive prior treatment and/or disease
- prolonged disease-free interval
What are the options for chemotherapy for breast cancer?
- single vs combination
- TNBC
- PD-L1 status
- HER2(+)
- BRCA status
The recommended 1st line options for HER2+ metastatic disease
- Trastuzumab
- Pertuzumab
- Docetaxel (or paclitaxel)
What is the recommended treatment in HER2 low patients?
- Fam-trastuzumab deruxtecan
Hormone positive, LN- and +, HER2 -, tumor ≤ 0.5 cm
consider adjuvant endocrine therapy
1st line treatment for TNBC
- carboplatin or cisplantin single agent
- however, pembrolizumab + chemo is better in chemo alone in patients with a combined positive score ≥ 10
Hormone positive, LN- and +, HER2 -, tumor > 0.5 cm or 1-3 positive nodes, RT-PCR not done
adjuvant endocrine therapy or adjuvant chemo followed by endocrine therapy
Hormone positive, LN- and +, HER2 -, tumor > 0.5 cm or 1-3 positive nodes, RS < 26
adjuvant endocrine therapy
Hormone positive, LN- and +, HER2 -, tumor > 0.5 cm or 1-3 positive nodes, ≥ 26
adjuvant chemo followed by adjuvant endocrine therapy
HER2-, postmenopausal or premenopausal receiving OS metastatic hormonal therapy first line
- AI + CDK 4/6 Inhibitor (-clib)
Abemaciclib Monitoring Parameters
- CBC, diarrhea
Palbociclib Monitoring Parameters
- CBC
Ribociclib Monitoring Parameters
- CBC, QTc prolongation
Mammogram Screening
- Age 40-44 opportunity for annual exams
- Age 45-54 annual mammograms
Breast Cancer Prevention
- prophylactic mastectomy
- bilateral oophorectomy
- Tamoxifen and Raloxifene
Etiology/Patho of Prostate Cancer
- Hormonal: testosterone is a growth signal to the prostate
- Androgen receptor alterations
Risk Factors of Prostate cancer
- age
- AA, less common in Asians
Signs and Symptoms of Prostate Cancer
- asymptomatic with early disease
- alterations in urinary habits
- impotence
- lower extremity edema
- weight loss
- anemia
Prostate cancer metastasizes to what?
- the bone (most common)
- lung
- liver
Diagnosis of Prostate Cancer
- physical exam
- PSA
- transrectal ultrasound
- via biopsy of prostate
Importance of Gleason Score
- the higher the score, the higher the risk of extracapsular spread (increased growth rate)
PSA Diagnosis
- Normal range is 0-4 ng/mL
- > 10 ng/mL highly sus for malignancy
- PSA velocity: >0,5 ng/mL rise per year sus for malignancy
m1
metastatic prostate cancer
m0
non-metastatic on scans (PSA only)
HSPC
hormone sensitive prostate cancer
CRPC
castrate resistant prostate cancer
Localized Observation treatment for Prostate Cancer
- monitoring the course of disease with the expectation to deliver palliative therapy for the development of symptoms, a change in exam or PSA that suggests symptoms are imminent
When to check DRE and PSA in localized observation
q6months
Localized active surveillance for prostate cancer
- based on the premise that prostate cancer is a benign and indolent disease
- if cancer noted to progress, will initiate potentially curative therapy
Monitoring for active surveillance treatment: prostate cancer
- PSA, digital rectal exam, and symptoms
When to initiate treatment in prostate cancer?
- rising PSA or the development of symptoms
What are the three types of localized treatment for prostate cancer
- active surveillance
- radiation therapy
- surgery
Localized radiation therapy for prostate cancer
- reasonable alternative for patients who are not surgical candidates
- diarrhea, ED
- can add adjuvant ADT if intermediate or poor risk
locally advanced/high risk prostate cancer treatment
- ADT in combo with external beam radiation therapy
- Start ADT prior to RT and then continue during RT and for 1-3 years after radiation
Radial Prostatectomy + Pelvic lymph node dissection (PLND)
- definite curative therapy
Androgen deprivation therapy
- LHRH agonist ± anti-angdrogen or orchiectomy
- goal is to induce castrate levels of testosterone ≤ 50 ng/dL after 1 month
LHRH Agonist
- reversible and as effective as orchiectomy
- leuprolide (IM, SQ)
goserelin (SQ)
Acute LHRH agonist toxicities
- tumor flair (in the metastatic setting)
- gynecomastia
- hot flashes
- ED
- injection site reaction
- edema
Long term toxicities of LHRH agonists
- osteoporosis
- fracture
- obesity
- changes in lipids
- CV events
- increased risk of both diabetes
Relugolix
- compared to LHRH agonists and had less CV events
Anti Androgen Drugs
- flutamide
- bicalutamide (most common)
- nilutamide
- diarrhea
General first line for metastatic prostate cancer
- palliation of disease
- suppress testosterone
- need to determine whether this is a PSA recurrence or overt metastatic disease
metastatic disease m0HSPC with PSA doubling time < 6 months
can give ADT
metastatic disease m0HSPC with PSA doubling time > 6 months
can observe
Orchiectomy
- immediate drop in testosterone levels
- addition of anti-androgen therapy is of unknown benefit
- toxicities: impotence, hot flashes
What medication in prostate cancer causes disease flare?
- LHRH agonists
- anti-androgen should be administered to prevent disease flare
Intermittent ADT in m0HSPC
- can start on LHRN agonist alone or with oral ADT
- d/c when PSA level has returned to baaseline
- men with biochemical failure only
m0CRPC therapy
- continue ADT (usually an LHRH agonist)
- Add one of the following (Enzalutamide, aptalutamide, darolutamide)
Enzalutamide (Xtandi)
- blocks androgen binding and translocation of the androgen receptor
Enzalutamide Interactions
- avoid CYP2C8
- can decrease concentrations that are substrates for CYP3A4, 2C9, 2C19 (warfarin)
- caution in patients with a seizure history
- enzalutamide syndrome
Which medication does not have an indication in the M0 setting of prostate cancer
abiraterone
Apalutamide
- non steroidal androgen receptor inhibitor
- CYP 3A4 CYP 2C8
- use caution in patients with seizure disorder, QT prolongation
Darolutamide
- structurally unique androgen receptor antagonist
- offers potentially less toxicities and less severe toxicities
- less fractures, falls, seizures, weight loss
m1HSPC
- patient now has visceral metastasis
- hormone sensitive disease
Low volume m1HSPC treatment
- ADT: LHRH agonist or antagonists
- Continue ADT and add any of the following
- abiraterone + prednisone
- enzalutamide
- apalutamide
Abiraterone
- selectively and irreversible inhibits CYP17
- must give prednisone for adrenal insufficiency
High volume m1HSPC
Could do
- ADT
- ADT + Abiraterone + Prednisone
- ADT + Enzalutamide
- ADT + Apalutamide
or
chemo becomes an option
First line treatment for high volume m1HSPC
- Docetaxel + ADT (abiraterone or darolutamide)
- visceral metastasis
- 4 or more bone metastases
- at least one metastasis beyond the pelvis vertebral column
Docetaxel in M1HSPC
- more neutropenic fevers
- more neuropathy
m1CRPC
- hormone refractory
- Sipuleucel-T
- Docetaxel (alone or in combo with abiraterone or darolutamide)
- Cabazitaxel (second line if already on docetaxel)
Cabazitaxel
- poor affinity for MDR proteins, conferring activity in resistant tumors
- more severe neutropenia, more diarrhea, more febrile neutropenia
Prostate Cancer Screening Options
- DRE
- PSA
- transrectal ultrasonography
ACS Screening guidelines Prostate Cancer
- men ≥ 50
- PSA±DRE
- annual screening if PSA ≥ 2.5 ng/mL
- PSA ≥ 4.0 ng/mL refer
Prostate cancer prevention
- finasteride
- those who are on finasteride that developed prostate cancer had disease wit increased Gleason score
