Cancer Sucks Flashcards
(223 cards)
1
Q
What are the negative effects of chemotherapy-induced N/V?
A
-increases morbidity
-negatively effects patients quality of life
-more distressful for the patients compared to other side effects
-non-adherence to chemotherapy and/or dose-reductions
-weakness, dehydration, electrolyte imbalance, esophageal tears, decline in behavioral and mental status
2
Q
Acute CINV
A
-occurring within the first 24 hours after initiation of chemotherapy
3
Q
Delayed CINV
A
occurring from 24 hrs to several days (days 2-5) after chemotherapy
4
Q
Breakthrough CINV
A
occurring despite appropriate prophylactic treatment
5
Q
Anticipatory CINV
A
occurring before a treatment as a conditioned response to the occurrence of CINV in previous cycles
6
Q
Refractory CINV
A
recurring in subsequent cycles of therapy, excluding anticipatory CINV
7
Q
Pathology of CINV
A
-communication between several neurotransmitters and receptors in the CNS & GI tract
-Serotonin and its receptors
-Substance P and NK-1 receptors
-Dopamine and its receptors
8
Q
Emetic response to chemotherapy: Peripheral pathway
A
-5-HT3-mediated
-originates in the GI tract
-activated in the first 24hr after chemotherapy
-primarily associated with acute emesis
9
Q
Emetic response to chemotherapy: central pathway
A
-NK-1 receptor mediated (substance P as well)
-occurs primarily in the brain
-through to be predominantly involved in delayed CINV
10
Q
general principles of emesis control
A
-PREVENTION is key!!
-factors in choosing antiemetic agents: emetic risk of the therapy, prior experience with antiemetics, pt factors
**for chemo regimens with multiple agents, anti-emetic prophylaxis should be based on the agent with the highest emetogenic risk
-lifestyle measures may help to alleviate CINV
11
Q
Risk factors of CINV
A
-age < 50
-female sex
-emetic potential of chemotherapy
-little or no previous alcohol use
-hx of CINV: prone to motion sickness
-emesis during pregnancy
12
Q
Emesis Prevention: HIGH emetic risk w/ parenteral anticancer agents
A
Day 1: olanzapine, dexamethasone, NK1 RA, 5-HT3 RA
Day 2-4: olazapine, dexamethasone, aprepitant (PO)
13
Q
Emesis Prevention: MODERATE risk w/ parenteral anticancer agents
A
A: day 1: dexamethasonse & 5-HT3 RA, Day 2-3: Dexamethasone OR 5-HT3 RA
B: day 1: olazapine, dexamethasone, palonosetron
Day 2-3: olanzapine
C: day 1: NK1 RA, dexamethasone, 5-HT3 RA
Day 2-3: Aprepitant +/- dexamethasone
14
Q
Emesis prevention for low/minimal emetic risk
A
Options:
-dexamethasone
-metoclopramide
-prochlorperazine
-5-HT3 RA
15
Q
Emesis prevention with ORAL anticancer agents
A
-high to moderate emetic risk: 5-HT3 RA
-low to minimal emetic risk: PRN recommended
16
Q
Breakthrough emesis treatment
A
-add one agent from a different frug class to the current regimen
-consider routine, around the clock admin rather than PRN dosing
-consider antacid therapy if pt has dyspepsia
-drug options: olazapine, lorazepam, dronabinol, 5-HT3 RA, prochloperazine, dexamethasone, metoclopramide, scopolamine
17
Q
Anticipatory emesis treatment
A
-PREVENTION is key!
-avoid strong smells that may precipitate symptoms
-LORAZEPAM is useful in anticipatory, anxiety-related, emesis
-acupunture
-behavioral therapy: guided imagery, relaxation, hypnosis, cognitive distraction, yoga, biofeedback, progressive muscle relaxation
18
Q
Dexamethasone used in CINV
A
-MOA unknown –> Drug of choice!
-AEs: insomnia (administer in the AM), dyspepsia (take with food, consider adding H2 antagonist or PPI as clinically indicated), hyperglycemia, hypertension
19
Q
5-HT3 RA used in CINV (ondansetron, palonosetron, granisertron)
A
MOA: blocks serotonin, both peripherally on vagal nerve terminals & centrally in the chemoreceptor trigger zone
AEs: headache, constapation, QTc prolongation
20
Q
5-HT3 RA used in CINV: Ondansetron & Granisetron
A
-1st generation
-most effective in preventing of acute CINV
-short acting –> can be used in breakthrough nausea
21
Q
5-HT3 RA used in CINV: palonosetron
A
-2nd generation
-effective in preventing acute & delayed CINV
-long acting ( 1/2 life = 40 hrs)
22
Q
NK1 RA used in CINV: (aprepitant, fosaprepitant, rolapitant, fosnetupitant, netupitant)
A
MOA: inhibits the substance p/ neurokinin 1 –> augments 5HT3-RA & dexamethasone antiemetic activity
-only used for PREVENTION of CINv, not treatment
-DDIs: inhibition of CYP3A4 and CYP2C9 (dec dexamethasone dose to 8 mg daily on days 2-4)
AEs: fatigue, GI upset, headache, hiccups
23
Q
Olanzapine used in CINV
A
MOA: blocks dopamine, 5-HT3, muscarinic and histamine receptors
–> useful in both prevention and breakthrough nausea
AE: sedation (administer at bedtime, consider low dose for elderly), hyperglycemia, fatigue, QTc prolongation
24
Q
Dopamine antagonists used in CINV (Prochloperazine, Metoclopramide, Promethazine)
A
MOA: antagonize dopamine in the chemoreceptor trigger zone, most useful for breakthrough CINV
P&P AEs: phenothiazines, drowsiness, constipation
M AEs: benzamines, drowsiness, diarrhea, QTc prolongation, tardive dyskinesia
*Prochlorperazine used in pts at risk of QTc *
25
Benzodiazepines used in CINV (lorazepam, alprazolam)
MOA: anxiolytic
--> most useful for anticipatory CINV or breakthrough CINV that has an anxiety component
--> administer the night before or the morning of chemotherapy or both
AEs: sedation, dizziness
26
Cannabinoids used in CINV (dronabinol)
MOA: CB1 agonism suppresses vomiting, indirect activation of 5HT1a in raphe nucleus
--> rarely used, only indicated for refractory disease
AEs: sedation, euphoria, hallucinations, palpitations, flushing, cough
27
Scopolamine used in CINV
MOA: anticholinergic
--> rarely used, only used for breakthrough disease
AEs: dry mouth, somnolence, blurred vision
28
Cancer treatment induced diarrhea (CTID)
-can cause depletion of fluids and electrolytes, malnutrition, dehydration, and hospitalization/death
-can also be related to chemotherapy dosing delays or reductions
29
Assessment of CTID
-hx, volume and duration of diarrhea, hydration status
added risk factors: fever, orthostatic symptoms, abdominal pain.cramping, weakness
30
Diarrhea grading: grades 1 & 2
1: < 4 stools/day, mild increase in ostomy output
2: 4-6 stools/day, moderate increase in ostomy output, limiting instrumental ADL
31
Diarrhea grading: grades 3 & 4
3: > 7 stools per day, hospitalization indicated, severe increase in ostomy output, limiting. self care ADL
4: life threatening consequences, urgent intervention indicated
32
*Irinotecan-induced diarrhea
**Irinotecan can cause acute or delayed diarrhea
--> acute: due to cholinergic stimulation, mean duration of symptoms is 30 mins, usually respond rapidly to atropine
--> delayed: due to GI mucosal damage secondary to SN-38, usually occur more than 24 hrs after admin, noncumulative and occurs at all doses
33
Management of CTID
Non-pharm: avoidance of foods that would aggravate the diarrhea, aggressive oral rehydration with fluids that contain water, salt and sugar
Pharm:
-1st line: loperamide ( 4 mg then 2 mg q 4 hrs after MDD 16 mg) --> OTC
-Diphenoxylate-atropine (1-2 tabs q 6 hr until control achieves (MDD 8 tab)
34
tx of refractory CTID
-Octreotide
-tincture of opium
-probiotics
-rule out C. diff and infection colitis
35
Mucositis
-erythematous and ulcerative lesions of the mucosa observed in pts treated with chemotherapy
-can occur anywhere in the GI tract
36
Stomatitis
mucositis limited to the oral cavity
37
Mucositis complications
-symptom onset: typically occurs within 5-14 days
-dec oral intake: poor nutritional status, grade 3 = severe oral pain, grade 4 requires parenteral or enteral nutrition
-inc infection risk: gram _ oral flora, candida or fungal infection
-pain: may require opioids and PCA admin
38
5 stage model of oral mucositis
1) initiation: cellular damage induced, reactive oxygen species formation
2) primary damage response: activation od. p53 & NK-kB
3) signal amplification: release of inflammatory cytokines, tissue damage & cell death
4) ulceration: high risk for bacterial colonization
5) healing: cessation from ongoing tissue damage
39
risk factors of chemotherapy induced mucositis
-chemotherapy: melphalan, cisplatin + radiation, high-dose methotrexate, doxorubicin, busulfan, 5-FU
-patient factors: smoking, poor oral hygiene, oral lesions at baseline, female sex, pretreatment nutritional status
40
Prevention of chemo-induced mucositis
--> oral hygiene: avoid acidic or spicy foods, brushing with a soft toothbrush BID & flossing, switch tablets to solutions or IV, use nonalcohol-based mouthwashes at least QID
--> cryotherapy: local vasoconstriction --> less drug delivered to the oral mucosa, hold ice chips in their mouth for 30 mins before and/or during infusion of chemotherapy
41
Management of chemotherapy-induced mucositis
1- oral decontamination: bland mouthwash or oncology mouthwash --> dexamethasone mouthwash for Everolimus-induced mucositis
2- pain control: 2 % viscous lidocaine swish and spit, systemic opioids
3- palliation of dry mouth: artificial saliva products or chewing gum to increase saliva production
4- nutritional support: liquid or soft diet, TPN
5- oral candidiasis tx: nystatin oral solution or clotrimazole lozange, floconazole 200 mg PO x 1 dose, then 100 mg x 21 days
42
Neutropenia
-absolute neutrophil count < 500 or expected to decrease < 500 in 48 hrs
--> profound neutropenia: ANC < 100
--> prolonged neutropenia: lasting longer than 10 days
--> febrile neutropenia: single temp > 38.3 orally or > 38.0 over 1 h + ANC < 500 or expected to decrease to < 500 cells in 48 hrs
43
Consequences of neutropenia
-dose reduction or treatment delays
-compromise clinical outcomes
-longer hospital stays
-increased treatment costs
-decreased quality of life
44
Risk assessment for febrile neutropenia
-disease
-chemo regimen: high. dose therapy or dose-dense therapy
-patient risk factors: prior chemotherapy or radiation therapy, persistent neutropenia, bone marrow involvement by tumor, recent surgery and/or open wounds, liver dysfunction, renal dysfunction, age > 65 years receiving full chemotherapy dose intensity
45
Primary prevention for febrile neutropenia
--> high risk, regardless of pt risk factors: G-CSFs recommended
--> Intermediate risk + >/- 1 risk factor: consider G-CSFs
--> low risk + >/- 2 risk factors: G-CSFs may be considered
46
Primary prevention for febrile neutropenia : Filgrastim, tbo-filgrastim (catergory 1) *
-short acting G-CSF
-start the next day or up to 3-4 days after completion of chemotherapy
-given daily until ANC recovery
47
Primary prevention for febrile neutropenia : Pegfilgrastim (catergory 1)*
-long acting G-CSF
-adminster up to 3-4 days after completion of chemotherapy
-single adminstration
**allow >12 days between the dose of pegfilgrastrim and the next cycle of chemotherapy
48
Primary prevention for febrile neutropenia : Eflapegrastim-xnst (catergory 2A) *
-long acting G-CSF
-administer ~ 24 hrs after completion of chemotherapy
-single dose admin
*-do not administer 14 days before and 24 hrs after admin of chemotherapy
49
Treatment of febrile neutropenia
-received filgrastim prophylactically: continue filgrastim
-received pegfilgrastim or eflapegrastim-xnst prophylactically: no additional G-CSFs needed
-did not receive prophylactic G-CSFs: assess risk factors for an infection-associated complication
50
TX of febrile neutropenia: possible indications for G-CSF use in established febrile neutropenia
-sepsis syndrome
-age > 65
-ANC < 100
-neutropenia expected to be > 10 days in duration
-pneumonia or other clinically documented infections
-invasive fungal infection
-hospitalization at the time of fever
-prior episodes of febrile neutropenia
51
Secondary prevention for febrile neutropenia
in lue of febrile neutropnia or dose-limiting neutropenic event:
--> prior use of G-CSFs: consider chemo dose reduction or change in tx regimen
--> no prior use of G-CSFs: consider G-CSFs
52
Acute Leukamias
-rapid onset
-symptomatic
-rapidly fatal if untreated
-immature cells ("blasts")
-usually leukopenia
53
Chronic Leukemias
-slowly progressive
-most asymptomatic
-some survive years without treatment
-immature and mature cells
-
54
Diagnosis of leukemia
-bone marrow responsible for production of circulating blood cells --> includes red blood cells, white blood cells and platelets
-bone marrow aspirate and biopsy required for diagnosis --> allows one to sample space where hematopoiesis occurs
55
who gets AML?
-most common acute leukemia in adults aged 65-74
-most deadly leukemia in the US annually
-median age at diagnosis: 68 y/o
56
Signs and Symptoms of AML
-anemia: fatigue, SOB
-thrombocytopenia: bleeding risk
-neutropenia*: defined as absolute neutrophil count < 500 or < 1000 with anticipated decreased to < 500 within 48 hrs
-spontaneous tumor lysis syndrome
-CNS involvement (rare): somnolence, headaches, confusion
57
What does AML look like?
-pancytopenia, WBC within normal limits, present with elevated WBC
-hyperleukocytosis
-elevated WBC: arbitrarily defined as WBC > 100,000, poor prognosis, increases risk of CNS involvement & very high risk ot TLS
58
What is hyperleukpcytosis in AML?
--> oncologic emergency
-hyperviscosity syndrome - "blood slugging"
-stupor, SOB, vision changes
-stroke, responsibility failure, cardaic ischemia, renal failure, retinal hemorrhage
59
Management of hyperluekocytosis
Hydroxyurea (Hydrea)
-oral ribonucleotide reductase inhibitor
-used for "count control"
-used until clinically stable and ready to start induction chemotherapy
-leukophresis
60
Hydroxyurea
-used for management of hyperluekocytosis
-capsules and suspension
-AEs: N/V/diarrhea, tumer lysis,
--> long term toxicities: cutaneous vasculitic ulcerations, mucositis, alopecia and hyperpigmentation
61
Diagnostic criteria for AML
-WHO: > 20% blasts isolated on bone marrow biopsy or peripheral blood
-detection of cytogenetic abnormalities known to indicate AML regardless of blast % on bmbx
62
Prognostic Markers of AML
**cytogenetics: karyotype (a persons chromosomal make up--> predicts ability to obtain remission with induction chemotherapy, risk of relapse and overall survival
-molecular abnormalities, age, primary vs secondary AML, performance status, availability of a stem cell donor, WBC at diagnosis, extra medullary disease
63
FMS-like-Tyrosine Kinase (FLT3) mutations
-promotes proliferation and blocks differentiation
-associated with worse prognosis, increased relapse rate and lower OS
-associated with leukocytosis and high percentage of blasts in bone marrow in denovo AML --> ITD mutation is associated with worse survival/worse prognosis compared to TDK mutation
64
Criteria for high-intensity induction chemotherapy for AML
-most pts < 60 y/o
-pts > 60 y/o without significant co-morbidities or end organ dysfunction
-pts with aggressive disease course
-pts who are candidates of an allogenic stem cell transplant
65
Induction chemotherapy: "7+3" for AML
-cytarabine 100 mg/m IV daily continuious infuction x 7 d + daunrorubicin 60 mg/m2 x 3d (OR idarubicin 12 mg x 3d)
--> 70% CR for < 60, 50% CR for > 60
66
When do you use Midostaurin in AML tx?
-FLT3-ITD or FLT3-TDK postitive pts
-50 mg BID with food on days 8-21 of each course of chemo
67
When do you use Gemtuzumab Ozogamicin (GO) in AML tx?
-favorable/intermediate cytogenetics
-3 mg.m^2 on days 1, 4 and 7 of induction & day 1 of consolidation courses
68
When do you use Liposomal Daunorubicin + Cytarabine (Vyxeos) in AML tx?
-use with treatment related AML/secondary (past radiation/cancer)
-1:5 fixed molar ratio
69
Response criteria in AML
-"leukemia-free state" - day 14 bmbx (goal is < 5-10% blasts, hypocellular)
-complete remissio/complete response criteria = day 28+ (assessed on repeat bmbx when blood counts recover after chemotherapy
70
Criteria for complete remission in AML
< 5% blasts AND ANC > 1000/mcL AND platelets > 100,000
71
Criteria for complete remission with incomplete count recovery (CRi) in AML
-older pts with prior MDS- residual dysplasia prevents full platelet recovery
72
AML post-remission therapy (for those who receive intensive chemo ONLY)
-high dose Cytarabine (HiDAC)
--> for those who recieve "7+3" based therapies
--> 1.5-3 g/m^2 IV q 12h x 6 doses every 28 days x 3-4 cycles
-addition of Midostaurin for FLT3+ or addition of GO on day 1 for cycles ! & 2 ONLY (for those that received GO in induction)
73
"low intensity chemo"--> for those unfit for intensive chemo/co-morbidities"
-hypomethylating agents + venetoclax
-low dose Cytarabine + Venetoclax
-Ivosidenib + Venetoclax
-LDAC + Glasdegib
74
AML Therapies: Midostaurin
FDA approved for newly-diagnosed FLT3 + AML (not refractory)
-targets FLT3 mutations (FLT3-ITD & TKD)
75
AML Therapies: Ivosidenib
-FDA approved for newly diagnosed AML & relapsed/refractory AML with IDH1 mutation
76
AML Therapies: Enasidenib
-FDA approved for replased/refractory AML with IDH2 mutation
77
Supportive care in AML*
1- transfusions: red blood cell transfusion if Hgb <. 8, platelet tranfusion if platelet < 10,000
2- infection prophylaxis while neutropenic: HSV/VZV (Acyclovir), antibacterial (levofloxacin), invasive fungal & mold (posaconazole ER)
78
Tumor Lysis Syndrome: Oncologic Emergency
-rapid tumor breakdown following chemotherapy (spontaneously may occur prior to start of chemo if high tumor burden
-sudden release of intracellular potassium, phosphorus, uric acid
--> onset = 12-72 hrs post chemo
79
Tumor Lysis Syndrome Presentation: metabolic disturbances *
-hyperuricemia: concentrates & crystalizes in urine --> may lead to irreversible kidney damage
-hyperphosphatemia: calcium phosphate product precipitates in kidney
-hyperkalemia
-hypocalcemia: elevated phosphorus leads to shift of Ca, Ca usually shifts to bone, but can go elsewhere --> may still lead to precipitates
80
Tumor Lysis Syndrome Prophylaxis
*allopurinal
-*hydration: maintain urine output > 2.5 L/day
-Rasburicase: only used for those at high risk & pre-existing hyperuricemia
81
Tumor Lysis Syndrome Management
-hyperuricemia: IV hydration
-Hyperkalemia: insulin & glucose
-Hyperphosphatemia: sevelamer, calcium acetate
-hypocalcemia: DO NOT treat
82
AML chemo clinical pearls: Anthracyclines
(daunorubicin, Idarubicin, Mitoxantrone)
-pink/red urine (mito = blue urine)
=myelosuppression
-cardiac toxicity --> alwasy do an echo
83
AML chemo clinical pearls: Cytarabine
neurotoxicity
-cerebellar syndrome --> ataxia, nystagmus, dysarthria
-"neuro checks" required prior to each visit
-conjuntivitis (Dez 0.1% eye drops q6h for 3 days after HiDAC is complete
84
AML chemo clinical pearls: GO
(Gemtuzumab)
-infusion-related reactions: pre-medicate with acetaminophin, diphenhydramine and methylprednisolone
-BBW: hepatotoxicity
**dont use in transplant pts
85
AML chemo clinical pearls: low-intensity chemo
-constipation --> standing bowel medications
-low-moderate emetogenicity
-pre-medicate with ondansetron
86
Myeloid Growth Factors
-may be started after 14 bmbx in those who receive intensive chemo
-does NOT prevent neutropenia
-risk of potentiating leukemic cells
AEs: bone pain (used loratadine)
87
What does CML look like?
main mutation = Philadelphia chromosome (Ph+)
-risk factors: ionizing radiation
-symptoms: up to 50% of pts are asymptomatic, splenomegaly, anorexia, bone pain, purpura, unexplained weight loss, fatigue
88
CML classifications: chronic phase
-want to keep pts here
Goal: delay progression to AP/BP, eradicate philadelphia chromosome
89
CML classifications: accelerated phase
-10-19% blasts in peripheral and/or bone marrow
-goal: control WBC count, bring back to CP and avoid progression to BP
90
CML classifications: blast phase
> 20% blasts
Goal: survive induction, bridge to allogenic stem cell transplant
91
CML: Pre-tyrosine kinase ERA
-universally fatal
-temp control with
--> hydroxurea
--> busulfan
--> interferon-alpha (use for pregos)
92
CML TKI low risk score tx
1) Imatinib OR
-Bosutinib OR
-Dasatinib OR
-Nilotinib
93
CML TKI intermediate or high risk score
1) Bosutinib OR
-Dasatinib OR
-Nilotinib
94
T3151 mutation in CML treatment choices:
Asiminib
Ponatinib
95
Ponatinib AE (CML tx)
-elevated pancreatic enzymes
-hypertension
-skin toxicity
-thrombotic events
96
Imatinib AE (CML tx)
-edema/fluid retentoin
-myalgias
-hypophosphatemia
-GI (diarrhea, N/V)
97
Bosutinib AEs (TML tx)
GI (diarrhea, N/V)
-headache
-rash
98
Dasatinib AEs (TML tx)
-pleural/pericardail effusions
-bleeding risk
-pulmonary arterial HTN
99
What is a Gleason Score (in prostate cancer)?
-described how cancer cells look under a microscope
-cancers with lower Gleason scores (2-4) tend to be less aggressive, while cancers with higher Gleason scores (7-10) tend to be more aggressive
100
Goals of Prostate Cancer therapy
-localized disease: control disease and symptoms, decrease morbidity & mortality
-advanced or metastatic disease: palliation symptom relief, improve quality of life, prolong survival
101
Local disease very low & low recurrence risk (prostate cancer) in relation to expected survival
< 10 yrs: observation
10-20 yrs: active surveillance
> 20 yrs: active surveillance, extended beam radiation or radical prostatectomy
102
local disease favorable and unfavorable intermediate Recurrence Risk in prostate cancer
Favorable:
--> 5-10 yrs: observation
--> > 10 yrs: AS, EBRT, radical prostatectomy
Unfavorable:
--> 5-10 yrs: observation, or EBRT + ADT
--> > 10 yrs: RP +/- pelvic lymph node dissection
103
LHRH agonists in medical castration
-reversible method of androgen ablation
-as effective as surgical orchiectomy
-goal serum testosterone < 50 one month after starting therapy
-no direct comparative trials between agents
--> goserelin and leuprolide
104
LHRH agonist adverse effects*
acute: tumor flare, hot flashes, erectile dysfunction, edema, gynecomastia, injection site reaction
Long-term: osteoporosis, clinical fracture, obesity, insulin resistance, increased risk of diabetes, CV events, alteration in lipids (hyperlipidemia)
105
LHRH counseling points
-initial tumor flare caused by a surge in LH/FSH release
-increased testosterone production: resolved after 2 weeks
-baseline bone mineral density test before starting long-term ADT: calcium and vitamin D supp
106
LHRH ANTagonists for prostate cancer
-Degarelix: given SQ monthly
-Relugolix: PO
advantages: much faster drop in testosterone levels, no tumor flare
disadvantages: less flexibility in dosing schedule, high cost
107
Anti androgens for tx of prostate cancer
serve as a competitive inhibitor for the binding of dihydrotestosterone and testosterone
--> use 2nd gen agents: Apalutamide, Enzalutamide, Darolutamide
108
Castration Sensitive Prostate Cancer treatment options
-combined modality approach as initial therapy for castration sensitive (or naive) prostate cancer for select high risk and metastatic pts:
--> ADT _ Abiraterone or Alpalutamide or Enzalutamide
--> ADT with Docetaxel x6 cycles _ Abiraterone or Darolutamide: use this for high volume = visceral metastases, and/or 4 bone metastases with at least 1 metastasis beyond the pelvis
109
Castration Sensitive Prostate Cancer
-serum testosterone < 50 and disease progression
--> if PSA doubling > 10 months: monitor
--> if PSADT < 10 months: apalutamide, enzalutamide, darolutamide
110
Secondary hormone therapy for (M0 or M1) in CSPC
-1st generation antiandrogen (nilutamide, flutamide, or bicalutamide)
-corticosteroids
-antiandrogen withdrawal
-ketoconazole + hydrocortisone
111
First generation antiandrogens used in prostate cancer
-Apalutamide: seizure occured in 0.2% of pts --> permanently d/c in pts who develop a seizure during tx
-Darolutamide: no increase in seizure compared to placebo!!
-Enzalutamide: increased risk of seizures
112
Metastatic (M1) CRPC treatment: no prior doxetaxel/no prior novel hormone therpy*
Preferred:
-Abiraterone
-Docetaxel
-Enzalutamide
Useful in certain circumstances:
-radium-223 for symptomatic bone metastases
-sipuleucel-T
113
Metastatic (M1) CRPC treatment: prior novel hormone therapy/no prior docetaxel *
Preferred: docetaxel
useful in certain circumstances:
-cabazital/carboplatin
-olaparib for HRRm
-rucaparib for BRCA mutation
-radium-223 for symtomatic bone metastases
-Sipuleucel -T
114
Metastatic CRPC 1st line tx options
(metastases in the liver, lung, adrenal gland, peritoneum or brain)
-Docetaxel: can cause reversible alopecia
-Abiraterone: given with steroids to minimize signs of mineralacorticoid excess from tx
--> Zytiga: take on empty stomach
--> Yonsa: give with steroids
115
Radium-223 in prostate cancer
-used for symptomatic bone metastases and no visceral metastases prior to and after docetaxel therapy
-adminstered IV once a month for 6 months
116
Supportive care with prostate cancer
-treatment of androgen deprivation-induced bone loss in prostate cancer: Denoscumab
-Osteroporosis: Zoledronic acid
117
Tumor Lysis Syndrome
-TLS is a condition that occurs when a large number of cancer cells die within a short period --> cell contents are released into the blood
-most common disease- related oncologic emergency in hematologic malignancies
-can occur spontaneously or after initiation of chemotherapy
-most frequently occurs in pts with rapid proliferating, bulky, chemo-sensitive tumors
118
Laboratory tumor lysis syndrome
>2 of the listed metabolic abnormalities within 3 days before or 7 days after initiation of treatment:
-hyperkalemia (> 6), hyperuricemia (> 8), hyperphosphatemia (> 4.5), hypocalcemia (< 7) or for all of these: 25% increase from baseline
119
Clinical Presentation of TLS
-hyperkalemia: ECG abnormalities, cardiac arrest, fatigue
-hyperuricemia: acute kidney injury, crystal nephropathy
-hyperphosphatemia: acute kidney injury, GI upset, AMS
-Hypocalcemia: AMS, seizures, arrhythmias, tetany & spasms
120
High risk of TLS treatment
-hydration
-rasburicase: flat dose on 1.5 or 3 mg
-allopurinol
121
Clinical presentation of febrile neutropenia
Febrile: single temp > 38.3 or temp > 38 for over 1 hr
Neutropenia: ANC < 500 cells OR ANC < 1000 and expected to drop to < 500 in 48 hrs
--> febrile neutropenia is often the first and sometimes only sign than an immunocompromised pt has developed an infection
122
oral options for management of infections (low risk)
-cipro + augmentin
-levo
-moxi
-cipro + clinda
not appropriate for: pts on flouroquinolone prophylaxis at the time of diagnosis, pts with N/V
123
Inpatient management of infections (intermediate-high risk)
-IV therapy
-mono-therapy with a broad spectrum, anti-pseudomonal antibiotic: cefepime, pip/tazo, meropenem, imi/cilas, ceftazidime
124
when do you add MRSA coverage for infections in cancer pts?
-catheter related infections
-SSTI
-pneumonia
-hemodynamic insufficiency/sepsis
-mucositis
--> vanco, linezolid, daptomycin
125
Adding fungal coverage for infections in cancer pts
-fungal coverage is added later on in the course of febrile neutropenia in pts who:
--> do not respond to initial therapy in 4-7 days
--> have positive fungal markers (Beta-D-Glucan/Galactomannan)
--> have positive fungal cultures
Options: fluconazole, voriconazole, etc
126
Hypercalcemia of malignancy: treatment overview
--> goal is to treat underlying malignancy
-hold medications that can potentially worsen hypercalcemia (vit D, calcium, thiazide diuretics)
-HYDRATION: saline +/- furosemide
-IV bisphosphonates, RANK-L inhibitor
(secondary therapy: calcitonin, glucocorticoids)
127
clinical pearl of calcitonin
*limited to first 48 hrs due to tachyphylaxis
-max of 4 doses
128
clinical pearls of bisphosphonates
-zoledronic acid, pramidronate
-onset is 48-72 hrs, with Nadir taking 4-7 days --> dont add ore doses, may take longer to see effect
129
MASCC score
-high risk = < 21 (outpatient management, oral antibiotics)
-low risk = >/ 21 (inpatient management, IV antibiotics)
130
Local NSCLC: stage I-II
I: surgery
II: surgery followed by adjuvant therapy
-platinum-based regiment +- novolumab in pts who are medically inoperable
-osimertinib (EGFR+) for up to 3 yrs
-Atezolizumab (PD-L1 > 1%) following completion of platinum-based chemotherapy for 1 yr
131
locally advanced NSCLC: stage III
IIIA:
-neoadjuvant chemotherapy +- nivolumab for 4 cycles followed by surgery or RT
-adjuvant osimertinib (EGFR+) or atezolizumab (PD-L1 > 1%)
-concurrent chemoradiotherapy for non-surgical candidates
IIIB-IIIC: considered unresectable disease
-concurrent chemoradiation is the mainstay for up to 6 cycles or until progression or unacceptable toxicity
-Durvalumab maintenance for 1 yr upon response to chemo
132
Cisplatin AEs
myelosuppression
N/v
diarrhea/constipation
oral mucositis
alopecia
nephrotoxicity
ototoxicity
peripheral neuropathy
133
Carboplatin AEs
-thrombocytopenia
-diarrhea/constipation
-oral mucositis
-alopecia
134
Calvert equation to dose carboplatin: dose based on renal function*
total dose (mg) = AUC x (CrCL + 25)
135
Epidermal Growth Factor Receptor (EGFR) Inhibitors used in lung cancer tx
1st line: Osimertinib (improved CNS activity, tolerability is better)
-EGFR mutations most prevalent in adenocarcinomas and non smokers
-not dependent on pH absorption
AEs: skin rash, dry skin, diarrhea, fatigue, nail toxicity, stomatitis, myelosuppression, QTc prolongation, conjunctivitis
136
ALK inhibitors in lung cancer tx
-Alectinib is the only ALKi that has demonstrated significant improvement in overall survival
Brigatinib: CYP3A4 substrate, diarrhea, fatigue, interstitial lung disease/penumonitis, myalgia, HTN
Alectinib: CYP3A4 substrate, constipation, fatigue, LFT abnormalities, peripheral edema, myalgia, anemia
Lorlatinib: CYP3A4, P-gp substrate, fatigue,peripheral edema, mood disorders, neuropathy, cognitive effects, arthralgia, weight increase
137
KRAS inhibitors in SCLC tx
-more commonly associated with cigarette smoking (confers poor prognosis) --> indicated for advanced or metastatic NSCLC and KRAS G12C mutation after receipt of one prior therapy
--> sotorasib: CYP3A4 and strong P-gp inhibitor, avoid coadminstration with PPIs and H2RAs (4 hours before or 10 hrs after)**, AEs: diarrhea, nausea, fatigue, LFT abnormalities
--> Adagrasib: CYP3A4 substrate, DOES NOT possess pH-dependent aborption, AEs: same as ^ + renal impairment, edema, QT prolongation, interstitial lung disease/pneumonitis
138
1st line therapy for PD-L1 >/ 50%
-pembrolizumab
-atezolizumab
-cemiplimab
139
1st ling therapy for PD-L1 1-49% or < 1%
-cisplatin/carboplatin + paclitaxel (squamous) + pembrolizumab
-cisplatin/carboplatin + pemetrexed (nonsquamous) + pembrolizumab
-cisplatin/carboplatin + paclitaxel (squamous) + nivolimab + Ipilimumab
-cisplatin/carboplatin + pemetrexed (nonsquamous) + nivolumab + Ipilimumab
140
**Immunotherapy related AEs in lung cancer
onset: within first few weeks-months after initiation but can occur anytime
Management:
--> grade 1: continue immunotherapy
--> grade 2: hold immunotherapy and consider corticiteroid administration
--> grade >3: hold immunotherapy and corticosteroid administration
-prednisone 0.5-2 mg/kg/day (refractory cases: add mycophenolate mofetil, infliximab
141
Vascular endothelial growth factor (VEGF) inhibitors in lung cancer
-cancer cells secrete angiogenic factors --> induce formation of new blood vessels (inc nutrient flow to permit growth and metastasis)
--> Bevacizumab, ramucirumab (cut off nutrient supply)
-Acute AE: HTN
-Delayed AE: thromboembolic events, epistaxis, major bleeds, GI perforation, diarrhea (ramucirumab)
-AVIOD in pts with squamous histology (bevacizumab), recent hemoptysis, in therapeutic anticoagulation for new onset WTE, recent surgical procedure
142
Chemotherapy agents in lung cancer tx: Taxanes
(paclitaxel, docetaxel)
-inhibits mytosis
-AEs: alopecia, peripheral neuropathy, hypersensitivity (pre med with dexamethasone, famotidine, diphenhydramine), peripheral edema (pre med with dexamethasone 8 mg BID day before, day of and day after infusion)
143
Chemotherapy agent in lung cancer tx: Pemetrexed
-depletes DNA building blocks
-primarily renal elimination --> avoid if CrCl < 45 (inc toxicities)
AEs: myelosuppression, erythematous/pruitic skin rash, fatigue, diarrhea, N/V --> give folic acid and VIt B, dexamethasone 4 mg BID before, of, after markedly diminishes incidence of skin rash
144
Small Cell Lung Cancer summary*
-rapidly dividing malignancy that spreads early in disease course
-60-70% present with extensive-stage disease
-tx of choice is chemotherapy +- radiation
-disease recurrence usually occurs within 6-8 months after complete response
-prophylactic cranial radiation (PCI) is offered upon partial response or CR to therapy
-recurrent disease is typically less responsive to chemotherapy
145
*limited and extensive stage SCLC chemotherapy regimens
1st line:
-cisplatin + etoposide
-Carboplatin + etoposide
-carboplatin + etoposide + atezolizumab
-carboplatin + etoposide + durvalumab
-Cisplatin + etoposide + durvalumab
2nd line:
-topotecan
-lurbinectedin
-clinical trial
146
**SCLC chemotherapy agents
-Etoposide: leads to double-stranded DNA breaks, AEs: myelosuppression, N/V, stomatitis, alopecia
-Topotecan: AEs: myelosuppression (neutropenia), diarrhea, N/V, fatigue, alopecia
-Lurbinectedin: use with pts who have severe renal dysfunction: AEs: fatigue, hepatic enzyme elevations, extravasation, nausea --> pretreat w/ dexamethasone
147
Signs and Symptoms of Lymphoma
-"B symptoms" (1 required): fevers, night sweats, weight loss (10% or more over 6 months or less)
-lymphadenopathy
148
DLBCL cytogenetics *
-distinction between translocations and amplified expression
-40% with adverse cytogenetics experience failure
--> BCL2 translocation: anti-apoptotic protein, resistance to chemotherapy
--> BCL6 translocation: blocks cycle progression and response to DNA damage
--> MYC: rearrangement within an IgG gene: double/triple-hit: MYC + BCL2 and/or BCL6 (high grade lymphoma)
--> TP53: 30% of all lymphomas
149
Subtypes of DLBCL*
-Diffuse large B cell lymphomas: germinal center B-cell types, activated B-cell type
-primary DLBCL of the CNS
-primary mediastinal large B-cell lymphona
-high-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements
-high-grade B-cell lymphomas, NOS
150
Gold standard frontline tx for lymphoma*
-goal is to cure ALL stages
-in fit pts, R-CHOP is considered gold standard:
R: rituximab
C: cyclophosphamide
H: Doxorubicin
O: Vincristine
P: prednisone
--> given every 21 days (usually 6 cycles)
151
Rituximab pharmacology in lymphoma tx
*MOA: chimeric monoclonal antibody binds to CD20
AEs: TLS, infusion reactions, GI perforation, hepatitis reactivation, progressive multifocal leukoencephalopathy, vaccinations are less effective
152
R-CHOP clinical pearls (R-C)
-Rituximab: infusion reactions - higher with bulky disease, LDH renal function, tumor lysis syndrome, hold 1st cycle is disease in GI tract
-cyclophosphamide pearls: contributes to alopecia, N/V (high risk anti-emesis regimen) & hemorrhagic cystitis (drink fluids!)
153
R-CHOP clinical pearls (HOP)*
*Doxorubicin: lifetime dose cap 450 mg/m2: monitor for cardiac dysfunction
*Vincristine: dose.cycle capped 2 mg: NO vines in the spine : fatal given intrathecally, give in small IV piggybacks, neuropathy
-Prednisone pearls: 100mg daily, hyperglycemia, steroid induced psychoses, insomnia
154
CHOP supportive care
-emetogenic risk = high: olanzapine use is indicated
-febrile neutropenic risk: growth factors (pegfilgrastim, filgrastim) routinely given
-viral reactivation: give PPX antiviral therapy for any patient who has had HBV
-tumor lysis syndrome: aggressive hydration, allopurinol
155
When is DA-R-EPOCH preferred over R-CHOP?
-double/triple hit Lymphoma
-primary mediastinal lymphoma
-HIV associated DLBCL
156
Follicular Lymphoma
-"indolent" B-cell lymphoma
-2nd most common BCL
-med age: 59
-incurable
157
Follicular Lymphoma 1st line tx clinical pearls
-Obinutuzumab: improved progression free survival, more infusion reactions
-rituximab maintenance preferred- improved PFS
158
Classical Hodgkins Lymphoma
-expresses CD30+ (CD20-)
-intracellular changes:
--> promotion of NF-kB pathways
--> JAk2 activation/overexpression
--> EVB enhances both
-expressed cytokines form a reactive shell
159
Nodular Lymphocyte-Predominant Hodgkin's Lymphoma
-CD20+, CD30-
-CD15- Ig+
--> can use retoximubab here
"popcorn cells"
160
Nodular Lymphocyte-Predominant Hodgkin's Lymphoma treatment
-CD20+ (CD30-, CD15-)
-ABVD +- rituximab
161
treatment of hodgkins lymphoma: ABVD*
-administered every 14 days, 2 doses per cycle:
-Adriamycin
-Bleomycin
-VinBLAStine
-Dacarbazine
162
Bleomycin AEs
MOA: binds to DNA, produces SS and DS breaks through generation of oxygen free radicals
-pulmonary fibrosis: PFT--> HIGHER risk when given with pegfilgrastim/folgrastim
163
Survivorship of Hodgkins lymphoma*
-high percentage of pts survive HL
-PMH + cancer is not inert or benign
--> secondary cancers: > 10 yrs later: lung and breast
--> cardiovascular disease
--> hypothyroidism
--> fertility
--> psychosocial complications
164
What are the parameters of anemia?
- < 13 g/dL in men OR <12 g/dL in women
causes: hypo proliferation, maturation disorder, maturation disorders, hemorrhage/hemolysis
165
Causes of Macrocytic anemia (> 100 fL)
folic acid deficiency, vitamin B12 deficiency, liver disease, alcohol, hypotension, drugs (sulfonamides, antineoplatics)
166
causes of Normocytuc anemia (80-100 fL)
-aplastic anemia
-anemia of chronic disease
-CKD
-hemolytic anemia
167
causes of microcytic anemia (< 80 fL)
iron deficiency
168
Iron Deficiency Anemia (IDA)
-most common form of anemia (children under 2 and pregos are at high risk)
-causes: blood loss via menstruation, GI bleeding, hemorrhoids, medication use (NSAIDs, corticosteroids, anticoagulants), alcohol, iron malabsorption
169
IDA Diagnosis
Iron panel:
-serum iron
-total iron-binding capacity
-% transferrin saturation
-serum ferritin --> MOST sensitive indicator of IDA (DECREASES)
170
IDA Treatment
Diet: animal liver, fortified ceeal, meat/fish,eggs,spinach, lentils
Supp: with with orange juice and ascorbic acid rish foods to increase absorption (mild and tea reduce iron absorption)
171
IDA tx: oral supplementation
-ferrous sulfate (20% elemental iron)
-ferrous sulfate exsiccated (30%)
-ferrous gluconate (12%)
-ferrous fumarate (33%)
dose every other day
172
Drugs that decrease Iron absorption *
-Al/Mg/Ca containing antacids
-tetracycline and doxycycline
-Histamine receptor-2 antagonists
-proton-pump inhibitors
-cholestyramine
173
Drugs decreased by iron*
-levadopa (decreases absorption)
-methyldopa (decreases efficacy)
-levothyroxine (decrease efficacy)
-penicillamine
-flouroquimolones
-tetracycline and doxycycline
-mycophenolate
174
IV Iron dosing*
generally Iron sucrose 200 mg IV x 5 days
-decrease dose if previously received pRBC transfusions: each pRBC contains ~200 mg of iron replacement (so for each transfusion they had, take away a dose - target is 1,000 mg)
175
Megaloblastic Anemia
-caused by abnormal DAN metabolism resulting in vitamin B12/folate deficiencies
Causes: hydroxyurea, zidovudine, cytarabine, methotrexate, azathioprine, 6-mercaptopurine
176
Lab finding in vitamin B 12 deficiency & tx
Lab results: ince MCV, MMA and serum homocysteine*
-Cyanocobalamin PO daily or IV/IM weekly, x4 weeks, monthly
177
Lab finding for folic deficiency & tx
increase MCV & inc serum homocysteine
-folic acid 1 mg daily, 4 mg in pregos
178
Anemia of inflammation (AI)
-one of the most common forms: increased incidence among elderly pts, results from chronic inflammation, malignancy or infection & can occur as early as 1-2 months after onset
Diseases causing: chronic infections (TB, HIV), COPD, gout, liver disease, alcoholic cirrhosis, HF
179
Labs supporting anemia of inflammation and tx
-DEC TIBC
-want to treat underlying conditions & consider packed red blood cell transfusions if pt is experiencing acute oxygenation complications or hgb < 7
180
when are ESAs used in AI treatment?
-approved for use in AI due to HIV, CKD, anemia from malignancy, myelodysplastic Syndrome
-only effective if bone marrow has adequate stores of iron, B12 & folic acid
-monitor hemoglobin: d/c if > 12
181
ESA Products
-Eopetin alfa: identical to endogenous human erythropoietin, 9 hrs 1/2 life
-Darbepoetin: slight amino acid difference, 1.2 life is 25 hrs
182
non modifiable risk factors of breast cancer
-female gender at birth
-older age
-fam hx
-personal hx
-genetics: BRCA1 and BRCA2
-breast changes found on biopsy
-ionizing radionation
-breast density
-easrly menarche/late menopause
183
modifiable risk factors of breast cancer
-nulliparity or older age at first childbirth
-postmenipausal hormonal replacement therapy
-postmenopausal obesity
-physical inactivity
-alcohol consumption
184
invasive breast cancers: common
-invasive ductal carcinoma: 75% of all invasive breast cancers, "limp", metastatic sites: bone, liver, lung, brain
-invasive lobular carcinoma: 5-10% of all invasive breast cancers, ill-defined thickening of the breast, metastatic sites: leptomeninges, peritoneal surfaces, retroperitoneum, GI tract, reproductive organs
185
Inflammatory breast cancer
-characterized by skin edema, redness, warmth and induration of underlying tissue
-cancer cells in dermal lymphatics on biopsy
-very rapid onset & poor prognosis
186
Staging of breast cancer
uses TNM staging (Tumor size, Nodal status, Metastases to distant site)
-early stage breast cancer (stages 0, I, II) & locally advanced breast cancer --> cure
-metastatic breast cancer (stage IV) --> palliation
187
Treatment options for invasive BC
-ER/PR+, HER2+ = chemo+HER2 + endocrine
-ER/PR+, HER2- = chemo + endocrine
-ER/PR-, HER2+ = hemo + HER2
-ER/PR-, HER2- = chemo
188
preferred chemo regiems for ER/PR(+-), HER2 (-) disease
-dose dense doxorubicin/cyclophosphamide (AC) x 4 doses --> paclitaxel every 2 weeks x 4 doses
-dose dence AC x 4 doses --> weekly paclitaxel x 12 doses
189
preferred chemo regimen for ER/PR -, HER2- disease (triple therapy)
Neoadjuvant
-pembrolizumab every 3 weeks x 4 doses + weekly paclitaxel/carboplatin x 12 doses --> pembrolizumab + doxorubicin/cyclophosphamide every 3 weeks x 4 doses
190
Preferred chemotherapy regimens: HER2+ disease
-docetaxel/carboplatin/trastuzumab +- pertuzumab every 3 weeks x 6 doses OR
-Paclitaxel + trastuzumab weekly x 12 weeks
191
Pertuzumab criteria
-needs > T2 or >N1, HER2 + tumor
-higher risk of recurrence
-post chemo, continue trastuzumab or pertuzumab/trastuzumab (MUST BE TAKEN TOGETHER) to. complete 1 yr
192
Counseling points for Taxanes (paclitaxel/docetaxel)*
-neuropathy (P>D)
-alopecia
-hypersensitivity reactions (infusion related)
-arthralagias/myalgias
-peripheral edema (D)
193
Counseling points for Doxorubicin*
**cardiotoxicity (dose related & IRREVERSIBLE!) --> get baseline ECHO or MUGA & q 3 months
-red secretions/urine discoloration
-secondary malignancies
-vesicant-extravasation (skin irritations/lesions- give drug with a port)
194
Counseling points for cyclophosphamide *
-hemorrhagic cystitis - significant bladder irritation due to active metabolite (acrolein)
-sterility
195
Counseling points for HER2 targeted therapy (trastuzumab/pertuzumab)*
*cardiotoxicity (CHF/ventricular dysfunction, not dose related & reversible) --> can hold drug & retrial
-diarrhea (P): all or nothing
-infusion reactions
196
Endocrine therapy: Tamoxifen*
-inhibits growth of tumors by competitively antagonizing estrogen at its receptor site
-prodrug w/ active metabolite being endoxifen
-AVOID strong CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion)
197
Adjuvant endocrine therapy for pre and post menopausal women*
Premeno: Tamoxifen, aromatase inhibitor + ovarian suppression
Postmeno: atomatase inhibitor + tamoxifen
198
What is ovarian suppression?
-oophorectomy (removal of ovaries)
-luteinizing hormone releasing hormone (LHRH): reversible, continuous stimulation of pituitary
--> decreases FSH and LH secretion, decreases estrogen production from ovaries
-goserelin 3.6 mg SQ q 28 days
-Leuprolide 3.75 mg IM q28 days
199
Endocrine therapy counseling points: Tamoxifen*
-menopausal symptoms (hot flashes, night sweats, vaginal. dryness)
-menstrual changes (premenopausal)
-uterine or endometrial cancer
-VTE, stroke
-pregnancy category D
200
Endocrine Therapy counseling points: aromatase inhibitors (anastrazole, letrozole, exemestane) *
-menopausal symptoms (hot flashes, night sweats, vaginal dryness)
-musculoskeletal symptoms (arthralgia, joint stiffness, bone pain)
-Inc bone loss (osterporosis/fractures)
-hypercholesterolemia
-cardiovascular risk
201
adjuvant zoledronic acid
-give to postmenopausal pts
- 4mg IV 1 6 months, contineu for 3-5 yrs
202
Endocrine therapy for metastatic breast cancer *
Palbociclib (Ibrance)
-used for tx of hormone receptor - positive, HER2- MBC
-used in combo with aromatase inhibitor as initial endocrine therapy & flivestrant with disease progression following endocrine therapy
-toxicity: fatigue, neutropenia, anemia, alopecia
203
Alpelisib endocrine therapy for MBC*
indication for hormone receptor-postitive HER2-, PIK3CA-MUTATED MBC in combo with fluvestrant
-toxicity: hyperglycemia, skin rash, diarrhea, nausea, fatigue, increased serum creatinine
204
HER2+ - MBC chemotherapy regimens
-Pertuzumab + trastuzumab + docetaxel
-Pertuzumab + trastuzumab + paclitaxel
205
MBC: bone metastases
-bisphosphonates (zoledronic acid, pamidronate)
-used for prevention of skeletal-related events, fractures, surgeries, radiation, spinal cord compression
-Denosumab: prevention of skeletal-related events
206
colorectal cancer
-most being as polyps on the innermost lining of the colon or rectum (mucosa) and can grow outward into blood vessels and nearby lumph nodes or distant organs
207
treatment of colorectal cancer based on stage
I: no adjuvant chemo
II: no treatment or adjuvant chemo
III: adjuvant chemo
IV: chemo, targeted therapy & immunotherapy
208
5-FU therapy in colorectal cancer
-inhibits thymidylate synthase, inhibiting DNA synthesis
--> folic acid helps to stabilize fdUMP binding to thymidylate synthase & enhances 5-FU cytotoxic effects
-Bolus AEs: myelosuppression
-continuous infusion effects: hand-foot syndrome, diarrhea, mucositis
209
Capecitabine tx of colorectal cancer
-pro-drug of 5-FU
-dose limiting toxicities: hyperbilirubinemia, diarrhea, hand-foot syndrome, mucositis
-radio-sensitizer (rectal cancer, potentiates the radiation
**CI in dihydropyrimidine dehydrogenase (DPD) deficiency (even if they are hetero- dont give)
210
Oxaliplatin-Induced Neuropathy vs. cold Sensitivity (acute)
Acute: see sensory- cold-induced paresthesias, cold induced pharyngeal dysesthesia alongside motor: cramps, jaw tightness/cracking, dysphonia
211
Oxaliplatin-Induced Neuropathy vs. cold Sensitivity (chronic & TX)
-cumulative
-S&S: distal sensory neuropathy, deep tendon reflex suppressed
Treatments: eating/drinking at room temp, GABA analogues, SNRI
212
Irinotecan for the treatment of colorectal cancer
-DIARRHEA
Acute onset: within 24 hrs, cholinergic excess (runny nose, increased saliva, watery eyes, shrinking pupils, sweating, flushing, cramps) --> atropine 0.4 mg SQ
Delayed onset: after 24 hrs, metabolism related --> loperamide *max 16 mg daily*
213
Anti-Angiogenesis Therapy for colorectal cancer
-Bevacizumab: approved for metastatic colorectal cancer with infusional 5-FU
-Ziv-aflibercept: approved in mCRC pts who have progressed on an oxaliplatin-based regimen
common toxicities: HTN, delayed wound healing (d/c 4 weeks before surgery & restart 4 weeks after), proteinuria (foamy urine), hemorrhage, arterial thrombosis, diarrhea, neutropenia
214
EGFR innhibitors in colorectal cancer (Cetuximab- chimeric, Panitumumab- recomb)
-must be KRAS-wild type!!
C: used 1st line with FOLFIRI
P: used 1st line with FOLFOX
Toxicities: infusion reactions, hypomagnesemia, paronychia, acneiform rash
--> prevention is key: limit sun exposure, avoid over drying skin, moisturize skin, avoid OTC acne products
215
EGFR inhibitors- rash. treatment (4 grades)
1: macular/papular eruption--> topical clindamycin 2% +- hydrocortisone 1%
2: eruption --> ^ or minocycline or doxycycline
3: macular, papular or vesicular eruption --> hold tx until grade 2, for 2nd or 3rd occurrence, dose reduce, for 4th occurence D/C
4: generalized exfoliative ulcerative or blistering --> d/c drug
216
Multikinase inhibitor- Regorafenib for colorectal cancer
-inhibits VEGFR 2 & 3, RET, KIT, PDGER & Raf kinase
-BBW: hepatotoxicity
-salvage therapy
217
Immunotherapy in colorectal cancer
-for MSI-H tumors only, typically in stage IV disease
-Pembrolizumab
-Nivolumab
AEs: colitis, rash, hepatitis, nephritis, pneumonitis
218
Colorectal cancer stage I tx
surveillance (no adjuvant therapy)
219
Colorectal cancer stage IIA - no high risk features tx
observation or consider capecitabine of 5-FU/Leucivorin (6 months)
220
Colorectal cancer stage IIA (high risk) IIB, IIC tx
-FOLFOX
-Capecitabine
-5-FU/leucovorin or capeOX or observation
221
Colorectal cancer stage III (low risk) tx
-capeOx preferred
-FOLFOX
222
Colorectal cancer stage III (high risk) tx
-CapeOx
-FOLFOX
223
colorectal cancer tx if pts cannot tolerate invasive therapy (old peeps)
-infusional 5-FU/Leucovorin +- Bevacizumab
-Capecitabine +- Bevacizumab
