Week 5 Flashcards
overviews of oncologic emergency categories
metabolic
*hypercalcemia of malignancy
*tumor lysis syndrome
hematologic
*febrile neutropenia
structureal
*spinal cord compression
Oncologic Emergency type
tumor lysis syndrome
Patho:
Clinical Presentation:
Risk factors:
Dx and workup:
Prevention:
Mgt/treatment plan:
Patho: occurs when large number of cancer cells die ithin a short period of time. cell contents are released into the blood. including dna, phosphate, potassium,-> leads to production of uric acid-> deposit in kidneys
Clinical Presentation:
Hyperkalemia (ecg abnomalities, cardiac arrest)
hypruricmemia(aki, crystal nephropathy)
hyperphosphatemia(ak, gi upset, ams)
hypocalcemia (ams, seizures, tetany)
Risk factors:
Cancer related: high proliferative, tumor bulk, circulating tumor cells, sensitivity to chemo
pt specific: elevated UA, nephropathy, hydration sttaus, hypotension, acidic uring, HF
Dx and workup:
lab TLS: >/2 or more of metabolic abnormalities w.in 3 days before or 7 days after initial trt.
*hyperkalemia>6
*hyperuricemia>8
hyperphosphatemia>4.5
*hypocalcemia</7
or 25% increase or decrease(calcium) from baseline
clinical tls: lab tls SS +
*aki
*seizures
*cardiac arrythmias
Prevention:
*hold causative agents
*hydration, avoid sodium bicarb
Mgt:
high risk: hydration, rasburicase, allopurinol
intermediate risk: hydration, allopurinol, consider rasburicase
low risk: observation, normal hydration, monitoring
mgt of TLS
allopurinol
moa:
indication:
dosing:
consideration:
mgt of TLS
allopurinol
moa: decreased formation of uric cid formation
indication: pt at risk for devloping tls. initiate 24 hrs before chemo
dosing: 300 mg po daily
consideration:
ddi
renal function
severe hypersensitivity
mgt of TLS
rasburicase
moa:
indication:
dosing:
consideration:
mgt of TLS
moa: reduce uric acif levels, wont inhibit uric acid formation
indication:preexsiting hyperuricemia
dosing: 1.5 mg or 3 mg
consideration:
leave blood samples on ice. heat can break down uric acid een more. put sample on ice,
refractory tls to rasburicase
use dialysis
rare
refractory volume overload, oligouria, and anuria
persistent hyperkalemia or hyperuricemia
hyperphosphatemia induced hypocalcemia
trt of hyperkalemia in tls
hydration- diuretics to optimize urine output
caclium chloride-stabilizes cardiac cell membrane
regular insulin: drives K intracellularly
sodium bicarb: drive K+ intracelularly by increasing ph
sodium polystyrene: promotes gi excretion of K
dialysis: removes K+ thorugh blood filtration
trt of hyperphosphatemia
first line: hydration
lmit dietary phosphate to 800-1000 mg/day
phophate binders: calcium acetate, calcium cabronate, aluminum hydroxide, lanthanum, sevelamer
last line dialysis
trt of hypocalcemia
resolves w. resolution of hyperphosphatemia
only trt symptomatic hyperphosphatemia to avoid overcorrection
Oncologic Emergency type
febrile neutropenia
Patho:
Clinical Presentation:
Risk factors:
Dx and workup:
Prevention:
Mgt/treatment plan:
Oncologic Emergency type
fever: single temp >38.3 OR temp>38C for over 1 hour AND ANC<500 or ANC<1000 and expected to drop to <500 in 48hrs
*often first and osmetimes only sign an immunocompromised pt has developed an infection
Patho:
Clinical Presentation:
Risk factors:
Dx and workup:
Low: anticipated <7 days
ntermediate: anticipated 7-10 days
high neutropenia >10 days
hx and physical, labs (cbc, renal function tests, lfts, electrolytes, microbe culture
Prevention:
low risk: none
intermediate: consider bacterial, funcal . use viral
high risk: use bacterial, consider fungal, and use viral
Mgt/treatment plan:
antimicrobials: levofloxcin and ciprofloxacin
pneumoccal: penecillin vk
antifungal: floconazole, posaconazole, voriconazole, micafungin, caspofungin
pneumocystisis: bactrim
viral: acyclovir
csf: Pegfilgastrim, filgastrim
Risk assessmen score: MASCC score
*high risk: <21
low risk>/21
low risk: outpt mgt-> oral abx
high risk pt: inpt mgt. broad spectrum iv abx
oral options for outpt management of febrile neutropenia
ciprofloxacin +augmentin
levofloxacin
moxifloxcain
ciprofloxacin +clindamycin
oraloptions not appropriate for pts on fluoro quinolones at time of diagnosis
pts w. N/V
in pt management of febrile neutropenia
iv therapy
monotherapy w. broad spectrum anti pseudamonal abx
cefepime
pip tazo
meropenem
imipenem
ceftazidime
double gram-coverage can be condisrd
mrsa coverage in febrile neutropenia
not covered unless specific indicaion
ex; catheter related infections
ssti
pneumonia
mucositis
fungal coverage in febrile neutropenia
fungal coverage added later on in course of febrile neutropenia..
only add if have + fungal markers (beta d glucan..) positive fungal cultures, doesnt respond to initial therapy in 4-7 days
trt: fluconazole, voriconazole, itraconazole, isavuconazole, posaconazole, liposomal amphotericin b
duration of treatment for fbrile neutropenia
unidentified infection
*continue untik
**anc >500
and afebrile >/2 days
identified infection:
ssti 7-14 days
blood stream infction: Gram-, 10-14 days: gram+ 7-14 days
bacterial sinusitis:7-14 days
bacterial pneumonia: 7-14 days
fungal (candida=2 weeks: mold=12 weeks)
Oncologic Emergency type
hypercalcemia of malignancy
Patho:
Clinical Presentation:
Risk factors:
Dx and workup:
Prevention:
Mgt/treatment plan:
Oncologic Emergency type
Patho:
humoral hypercalcemia: mediated by systemic secretion of PTH hormone. 80% of all cases
osteolytic hypercalcemia: increase osteoclastic bone resorption
vitamin d secreting lymphoma
ectopic hyperparathyoidism<1% cases
Clinical Presentation:
mild hypercalcemia: corrcted calcium
neurologic lethargy, confusion, irratibility, muscle weakness, etc.
Risk factors:
Dx and workup:
Prevention:
Mgt/treatment plan:
symptomatic hypercalcemia is an oncologic emergency
primary goal: treat underlying malignancy
hold medicines that can potentially worsen hypercalcemia
- HYDRATION: saline +/- furosemide (increase calciuresis)
primary therapies: iv biphosphonates, rank-l inhibitors
secondary therapies: calcitonin, glucocorticoids
biphosphonates
agents: zolendreic acid
pamidronate
inhibt bone resorption
takes up to 7-days to see effects
AE:!! flu like symptoms (pppx w. tylenol)!!, fevers arthralgias , neohrotoxicity,
denosumab
rank-l inhibitor reduce osteoclast acitivity
efficacy: 9-10 days
used in hyprcalcemia refractory to biphosphonates. use in pts w.evere renal impairment
toxicity: severe hypocalcemia, hypophosphatemia
calcitonin
inhibits bone resportion
can cause tachyphylaxis
other agents for hypercalcemia of malignancy
glucocorticoids: inhibits osteoclastic bone resoprtin by decreasing cytokines:
calcimemmetics (cinacalcet: effective for PTH carcinoma or primary/secondary hyperparathyroididm
dialysis: severe hypercalcemia due to renal insufficiency
*unable to hydrate pt
forms of lung cancer
2 forms of lung cancer
Non small cel85%) cmall cell(15%
Non small cell
*squamous (30) *non squamous70%)
Nonsquamous (
a)large cell (10%)
b)adenocarcinoma
clinical presentation of lung cancer
Clinical presentation of lung cancer
*pulmonary symptoms: cough dyspnea, chest pain or disocmfort, w. Or w.o hemoptysis
Extrapullmonary: fatigue, weightloss, anorexia
Paraneoplastic syndromes: hypercalcemia and siadh
disseminated disease can cause additional symptoms
most effective prevention in lung cancer
Most efective prevention in lung cancer:
*avoid tobacco
*maintain healthy diet high in fruits and vegetables
*offer screening to high risk individuals
general treatment goals for NSCLC
Treatment goals for NSCLC
*stage 1-11: cure
Stage III-Iv: prolongation of survival
Treatment goals for SCLC
Limited stage: cure
Extensive stage: prolongation of survival
local NSCLC (stage 1-2) trt
Stage 1:curgery
Stage 2:
Surgery followed by adjuvant therapy
Platinum based chemo regimen for 4 cycles
Osimertinib (EGFR+) for up to 3 years
Atezolizumab (PD-L1>/1%)
Neoadjuvant (therapy b4 surgery to shrink tumor down to increase chances of complete tumor removal
Radiation therapy
Reserved for pts who cant get surgery
local advanced stage nsclc (stage 3 tretment
Local advanced stage NSCLC (stage3) treatment
Stage 3a
Neoadjuvant chemo+/-nivolimumab
Adjuvant osimertinib (EGFR+) OR atezolizumab (PDL1>/1%)
Concurrent chemoradiotherapy for non surgical candidates
Stage 3b-3c
Considered unresectable disease
Concurrent chemo radiaion
Immunotherapy to increase progression free and overall survival
neoadjuvant regimens for nsclc
Neoadjuvant regimens for nsclc
Cisplatin or carboplatin incombo w. Other agents that are non platinum agents
*** pemetrexid only for nonsquamous histology only
cisplatn vs carboplatin
Cisplatin
Myelosupression
n/v
Diarrhea constipation
Oral mucosisitis
Alopecia
Nephrotoxicity (hypokalemia, hypomagnesemia)
Ototoxicity
Peripheral neuropathy
Carboplatin
Thrombocytopenia
Less n/v than cisplatin
diarrhea/ constipation
Oral mucositis
Alopecia
nephrotox(less than cisplatin)
Ototoxicity (less than cisplatin
Peripheral neuropathy (less than cisplatin)
Calvert equation: equation used to determine n dosing carboplatin based on pt renal function. Reduced risk of toxicities that we cant do w. Cisplatin
cisplatin equation
Total dose= AUCX(CRcL+25)
advanced nsclc stage 4 or relapsed trt
Advances nsclc: stave 4 or relapsed disease trt
If pt has targeted genetic mutation
Mutation in any: EGFR, ALK, ROS1,BRAF NTRK, RET, MET
Kinase inhibitor targeted to mutation
PDL1+>/50%
pd1/pdl1inhibitor+/-chemo
pdl1<1
Pdl1 inhibitor + chemo
advanced nsclc trt
EGFR inhibitors in nsclc
growth factor receptor inhibitors
Egfr mutations most prevalent in adenocarcinomas and non smokers
Agent examples
First (Erlotinib, gefitinib, afatinib
Second gen: (dacomitinib
Third: osimertinib FIRST LINEEE!!
Significantly improved PFS and os CAPERED TO FIRST GEN AGENTS, AND IMPROVED CNS ACTIVITY, BETTER TOLERABILITY
EGFR inhibitor AE
EGFR INHIBITOR AE:
Class adverse effects
Skin rash
Dry skin
Nail toxicity
Diarrhea
conjunctivitis
SPECIFIC drug side effects
Osimertinib
Cyp3a4 substrate
No ph dependent absorption
Myelosupression
Dose reduction for severe renal impairment
advanced nsclc trt
alk inhibitors
ALK INHIBITORS
Less common than egfr mutations
Seocnd and third gen superior improvement in outcomes
First gen: crizotinib, certinib,
Second gen: alectinib, brigatinib
Third gen: lorlatinib
advanced nsclc trt
alk inhibitor agent pearls
Brigatinib
Ddi: cyp3a4 substrate
Ph dependent absorption: no
AE: insterital lung disease/pneumonitis, myalgia, htn
Alectinib
Ddi: cyp3a4 substrate
Ph dependent absorption: no
AE: constipation, myalgias, lft elevation, anemias
Lorlatinib
Ddi: cyp3a4
Ph dependent absorption:
AE: depression, anxiety, has good cns penetration, weight increase
advanced nsclc trt
KRAS inhibiots
More common mutation sthat smoke cigarrettes
Pts with this have poor disease prognosis
Indicated for nsclc and kras g12c mutation after recepit of one therpay
advanced nsclc trt
kras inhibitor agent pearls
Sotorasinib
Ddi:cyp3a4 substrate
Ph dependent absorption:YES. Avoid ppis h2ra
AE:
Adagrasib
Ddi:
Ph dependent absorption: NONE
AE: renal impairment, qtc prolongation,
advanced nsclc trt
agents if pdl1 expression >50%
PDL1 expression level of >/50% or higher TReatments
Single agent immunotherapy
Pembrolizumab
Atezolizumab
Cemiplimab
advanced nsclc trt
pdl1 1-49%
PDL1 1-49%(BASICALLY MODERATE -low EXPRESSION)
Cisplatin or carpo +paclitaxel +permbrolizumab (squamous)
Cis or carb+ pemetrexed +pembrolizumab (non squamous)
Cis or carb +paclitaxel + nivolimumab
Etc.
advanced nsclc trt
2nd line trt
No previous checkpoint inhibitor: pembrolizumab, nivolumab, atezolizumab
Previous checkpoint inhibitor: docetaxel+ramucirumab(preffered over single agent), ramurcirumab +pembrolizumab, docetaxel, pemetrexed
immunothwrapy for nsclc patho
Immunotherapy for nsclc patho
Pd1l1: inhibits t cel killing of tumor cell-blocking allowst cell tumor killing
Ctla4: binding inhibits t cell acitivation: blocking potentiates t cell activation and killing
advanced nsclc trt
immunotherapy AE
Immunotherapy related side effects in nsclc
Onst: w.in first few weks to months after initiation but can occur anytime
Combing bdl1/ctla4 increases side effects
Different grades of AE
Grade1:continue immunotherapy
Grade 2: hold immunotherapy and consider admin prednisone
gradde3>: hold immunotherapy and give prednisone (or equiv)
Pred: 0.5-2mg/kg/day 5-7 days
Steroid refractory: mycophenolate, infliximab
advanced nsclc trt
VEGF inhibitors
VASCULAR ENDOTHELIAL GROWTH FACORS (VEGF)
Cancer cells form new blood cells, which increase nutrient flow and permit growth and metastasis
VEG F inhibitors
Nsclc specific agents: bevacizumab, ramucirumab
AE: HTN, thromboembolic events, major bleeds
Avoid in pts w, squamous histology (bevacizumab), recent hemoptysis, on tpx anticoagulation for new onset vte, recent surgical procedure.
chemo for lung cancer
Taxanes
Nsclc specific agents: paclitaxel, docetaxel
Moa: inhibits mitosis
AE: myelosupression, ALOPECIA, PERIPHERAL NEUROPATHY(dose limiting ae), hypersensitivity (premdicate to prevent), peripheral edema (docetaxel
Pemetrexed
Moa: inhibits DHFR. inhibit folate synthesis, causing cell death
Ci: severe renal dysfunction (crcl<45), NSAIDS decrease clearance
AE: dose limiting (myelosupression, skin rashes)
SCLC overview
Rapidly diving malignancy.
60-70% extensive disease stage
Poor prognosis
Trt of choice is chemo +/- radiation
SCLC trt first line and second line
Sclc treatment
First line
Platinum agents +/- other agents
Cisplatin+etoposide
Carboplatin+etoposide
Carbo+epot+atezolizumab (extensive only)
Carbo+epot+durvulomab (extensive only)
Second line
Topetecan
Lurbinectedin
Clinical trial
sclc trt agent pearls
Etoposide:
Moa: topoisomerase inhibitor
Dose limiting AE: myelosupression
Topotecan
Topoisomeras I inhibitor
Renal dosage adjustment
Myelosupression (neutropenia
Lurbinectedin
Moa: alkynates dna
Pk: cyp3a4 substrate
Fatigue, hepatic enzyme, extravasation, nausea
what is lymphoma
What is it
Cancers of the lymphoid lineage
Low incidence
global
Two major divisions
Hodkins
Non hodgekins
*Can either be bcell, t-cell, or nk cell
*Also classified as
Indolent
Aggressive
Very aggressive
mechanism of lymphomas
Mechanisms of infectious disease on causing l ymphomas : lymphocyte transforming viruses disrupt cell actiivty.
types of lymphona
TYpes of Lymphoma
B cell nhl
T cell/nk NHL
HL
all divided up further into indolent, agressive, or very aggressive
SS lymphadenoma
SS of lymphoma
Ymphadenoma
“B symptoms”
Fevers
Night sweats
Weight loss
Usually advanced disease
diffuse large b cell lymphoma
overview
Diffuse Large B-CELL lymphoma (DLBCL)
Most common heme malignancy in usa
Germinal center bcl vs activator center b cell
Gcb has greater survival than ABC
40% of pts w. Adverse cytogenetics will experience failure (not all inclusive)
prognosis of dlbcl
Prognosis of dlbcl
Best response to therapy: adherence of drug at specific dose
Anthracyclines are most impotant drugs (doxorubicine)
Fitness test
Who can fail?
AGE>60
STAGEIII-IV
ecog>2 (performance status … poorer activity)
LDH>UNL
trt for dlbcl
GOLD STANDARD FOR DLBCL
R-CHOP
R: rituxumab on day 0
C:Cyclophosphamide on day 1
H: Doxorubicin on day 1
O: vincristine on day 1
P: prednisone
Given q21 days for usually 6 days
trt of dlcbl
rituxumab
Rituxumab
Moa: mAb binds to CD20***
Increased OS by 15% when added to chop
Ae:
TLS
HOLD first cycle if tls risk is high
Infusino reactions, gi perforation, decrease efficacy of vaccines
Pearls: infusion directions, tls, hold if disease in gi tract
trt of dlbcl
cyclophosphamide
Cyclophosphamide pearls
Alopecia
High NV risk
Hemmorhagic cystitis/fluids
trt of dlbcl
doxorubicin
Doxorubicin pearls
Lifetime dose cap 450 mg/m2
Baseline ECHO due to nonreversible HF
Nv and mucositis
trt of dlbcl
vincristine
Vincristine pearls
Neuropathy (NO VINES IN SPINE)
Neuropathy in sensory (taste, smell, touch)
trt of dlbcl
prednisone
Prednisone pearls
Hyperglycemia
Steroid induced psychoses
Insomnia
trt od dlbcl
CHOP supportive care
Chop supportive care
Emetic risk high
Antiemetics
Febrile neutropenia
Pegfilgastrim and filgastrim
Viral reactivation (ritxumab)
Give ppx antiviral for pts who have had hbv
Tls
Aggressive hydration
Allopurinol
Hold rituxumab?
otions for pts w. poor lvef
Options for pts with poor lvef
Rceop
R-cepp
RCDOP
RGCVP
R-DA-EPOCH
alternative therapy for RCHOP
Alternative for RCHOP (new therapy)
Pola-R-CHP
Add polatuzumab, remove vincristine
PGS improved
Acts similarly to vincristine
DA-R-EPOCH
DA-R-EPOCH
Preferred over rchop in certain settings
duble/tripple hit lymphoma
Primarymediastinal lymphoma
Hiv associated dlbcl
relapsed/refracctory dlbcl
Relapsed /refractory disease
Auto transplant
Definitive cure in second line
Giving stem cells back after taking them and purifying them.
High dose chemo given to prior to overcome resistance
CAR T-CELL
Definitive cur in second line
T cells flagged w. Anti cd19 antibodies (found on lymphomas)
AE: cytokine release syndrome, neurotoxiciy
Very well response rate
Palliation
Use other moa therapies
follicular lymphoma
Follicular lymphoma(FL)
Indolent lymphoma
Rarely cured
Drugs work less
Indications fo treatment
Cytopenias
Consider grade, FLIPI score
Infections
Symptomatic disease
End organ function
Bulky disease
Change in aggressiveness diseas
First line trt of follicular lymphoma considerations
Obinutuzumab c rituxumab
Improves PFS
Infusion reactions
Rituxumab maintenance
BR v RCHOP
Relapsed refractory FL
Rule out transformation into DLBCL
DONT REPEAT SIMILAR REGIMENS
3RD LINE
Mosenutuzumab
Engaged cd3 t cells
AE: cytokine release syndrome
Complete response rate: 60%
hodgekins lymphoma overview
Hodgekins Lymphoma
B cell lymphoma arising from germinal center
Highly curable
Divided into 2 categories
Classical hodgkins lymphoma (cHL)
CD20 NEG, CD30+
Nodular lymphocyte-predominant hodgkins lymphoma(NLPHL)
Cd20 +, cd30 -
Main risk factors
Epstein barr virus
HIV
Patho of HL
CHL do not express traditional b cell markers (ex!!! Substitute CD30)
Very inflammatory cancer; a lot of pro inflammatory markers
NLPHL TRT
NLPHL TRT
CD20+ cd30-
RITUXUMAB + any chemo regimens
Classical HL TRT
ABVD
ADRIAMYCIN
BLEOMYCIN
VINBLATINE
DACARBAZINE
Pulmonary fibrosis
Infertility
Avoid in pulmonary function issues at baseline
AFTER 2 CYCLES, DO PET SCAN.
If refractory-> escalate to BEACOPP
If responsive, can remove bleomycin, to make AVD
Due to creation of free radicals, can cause pulmonary fibrosis, higher risk when given w. G-CSF (filgastrim and pegfilgrastim
Brentuximab
antiCD30
Side effects: neuropathathy
AAVD
Useful in some pts
High rates of neutropenia and neuropathy
Relapsed disease
Use different agent
