Download Bone Marrow Depression - leukopenia

Survey
yes no Was this document useful for you?
   Thank you for your participation!

* Your assessment is very important for improving the work of artificial intelligence, which forms the content of this project

Document related concepts

Serotonin syndrome wikipedia, lookup

Pharmacogenomics wikipedia, lookup

Neuropharmacology wikipedia, lookup

Toxicodynamics wikipedia, lookup

Neuropsychopharmacology wikipedia, lookup

Hormesis wikipedia, lookup

Bilastine wikipedia, lookup

Dydrogesterone wikipedia, lookup

Theralizumab wikipedia, lookup

Transcript
Bone Marrow Depression - leukopenia, neutropenia(ANC<500x10^9/L), lymphopenia, anemia(hypox, fatigue, CHF exacerb),
thrombocytopenia (<100worry, <10 or active bleeding-transfuse) Nadir - lowest point of WBC/platelet after chemo, usu 10-14days after tx
*Risk factors for neutropenia: A. Degree=ANC B. Immune system function – 1. Cellular (HIV, transplant, CS, lymphoma) 2. Humoral (dec.
gG, Bcell malig) C. defects in host defense – 1. Nutrition (ca pts don’t eat well) 2. Physical barriers (mouth/skin ulcers, altered gut flora,
invasive procedures) D. Patient Specific risk factors – Two Models to predict risk
Type I – predict severe or febrile neutropenia or reduced dose intensity. Risk Factors: age, performance status, dose intensity, serum LDH
Type II – predict bacteremiaor consequences of febrile neutropenia. Risk Factors: age, leukemia/lymphoma, high temp, low blood pressure
Other predictors: advanced age, myelosuppress chemo, perform status, depth of ANC nadir, precipitous drop in all hematopoietic CBC
I. Granulocyte colony stimulating factor (G-CSF,) filgrastim(Neupogen)-made w E. coli bacteria (recover neutrophils 4-5days sooner)
Pharmacol- lineage spec grow fact, glycoprotein for production, maturatation, function of cells of neutrophil lineage, focus on commit
progenitors, produced by many cell types. Pk/Pd- rapid absorption with SC admin (preferred), T1/2=3.5hrs, metabolic/elimination dose
dependent elevation in neutrophil count. Indications/dosing: 1. following myelosuppress chemo – 5mcg/kg/day SC 2.follow BMT- 510mcg/kg/day 3. peripheral blood progenitor cell mobilization and collection- 5-10mcg/kg/day SC; cont. through leukapheresis 4.
Cyclic/idiopathic neutropenia- 5mcg/kg/day SC Contraindications: simultaneous admin or admin within 24hr of chemo may potentiate
hematologic toxicity, hypersensitivity to hematologic growth factors or Ecoli, caution in pts w/ hairy cell leukemia, gout, psoriasis, preexist
cardiac conditions ADR: Common -Bone pain, fever, generalized rash, injection site redness, bruising. Less common – flare of bone scans,
transient neutropenia following IV infusions, dyspnea w/ infiltrates on chest x-ray in pts with underlying pulmonary disease Pegfilgrastim
(Neulasta)- Pharmacol- same differs in 20kD pegylated molecule attached to N-terminus, stimulates neutrophil lineage Pk/Pd- non-linear
kinetics (clearance decreased with increased dose), neutrophil receptor binding correlates with clearance of PEG-filgrastim, serum clearance
direct related to # of neutrophils, T1/2 15-80hrs following SC admin, time to Cmax 72hrs Indications/dosing: decrease infection incidence(due
to neutropenia), dose: 6mg admin once per chemo cycle. CIs: hypersensitivy to formulation ADR: Bone pain, fever, splenic rupture(due to high
WBC in spleen) II. Gran.macrophage-CSF Sargramostim – Pharmacology: glycoprotein w/ multilineage effects, induces partially committed
progenitor cells to divide/differentiate into gran-macropage pathways, stimulate neutrophils, monocytes, dendritic cells, eosinophils Pk/Pd:
rapid absorpt after SC admin, T1/2=2hrs, decrease in WBC/neutrophil count following discontinuation Indications/dosing: 1. following
autologous/allogenic BMT, BMT failure/engraftment delay, mobilization and follow transplantation of autologous peripheral blood progenitor
cells - 250mcg/m2/day SC CIs: hypersensitivity to formulation or yeast, caution in pts w/ preexist fluid retention, liver, lung, heart disease,
pleural/pericardial effusion simult admin or w/in 24hrs of chemo may potentiate hematologic toxicity. ADE: common-fever(low grade), bone
pain, myalgias, rash, inj site redness, bruising. Less common- dyspnea esp in preexisting lung disease, peripheral edema, capillary leak
syndrome, pleural/pericardial effusions III. Application of G-CSF and GM-CSF A. neutropenia assoc. w/ std dose chemo – more data w/ GCSF, prophylaxis after chemo shows signif reduction in incidence of febrile neutropenia, length of hospitalization, confirmed infections,
duration of abx. No effect on moratlity or tumor response rate or survival. Primary px- if chemo expected to cause >20% incidence of febrile
neutropenia. Secondary –pts who had neutropenic complication (infection/sepsis) with prior chemo cycle. B. Autologous BMT – growth fact.
reduce period of neutropenia, dec. hospitalization, abx use, infections; no effect on mortality or response rate. ii. Allogenic BMT – reduce
period of neutropenia, but no reduction in hospital stay or infection C. AML – i. initial caution b/c it is thought to stim leukemic cell growth
(do not give in active leukemia) ii. Priming during AML induction-not recommended outside clinical trial iii. After induction chemo-may
consid if benefit (reduce hosp) >cost iv. recommend. after consolidation chemo (in remiss/ no leukemia) IV. Admin. a. SC route preferred. b.
Timing-at least 24hrs after chemo finished (within 24-72hrs) c. endpoint GCSF,GMCSF- ANC at 2000-3000x10^9/L unless being used for
mobilization V. Oprelvekin (interleukin-11) –px severe thrombocytopenia in pts on chemo for non-myeloid malignancies Pharmacol- i.
growth fact. produced by stromal cell w/ activity on progenitor, Bcells, intestinal crypt cells, osteoclasts ii. Acts synergist w/ oth growth fact to
support prolifer of hemato progenitor cells iii. used clinically as platelet growth fact to stim magacaryocytopoiesis and thrombopoiesis. Pk/Pdterminal T1/2=6.9hrs, eliminated via kidneys, peak incidence in platelet count observed after 14-19days of therapy if admin alone with chemo,
cont’d increase in platelet count up to 7days after stopping treatmentDose: 50mcg/kg SC daily (do not round up) initiated 6-24hrs after chemo
complete & cont. for 14-21days or until post-nadir platelet count of >/=50,000 cells/mm3 is reached. Dosing beyond 21 days not ecommended.
must stop drug at least 48hrs prior to chemo. ContraInd.-hypersensitiv.Caution: left vent. dysfunc, arrhythmias, resp dx, thromboembolic
disorders, renal dysfunct, HTN. ADE: edema, SOB, tachy, eye redness, atrial arrythmias, peripheral edema, HA, dizzy, arthral/myalgia,
thrombosis in catheter. Drug must be admin w/in 3hrs of reconstitute. Monitor plts, heart rate, neuro status, s/sx of swelling, urine input/output,
eye exam Neutropenia= ANC < 500 **Neutropenic Fever; Fever= >/= 101F(38.3C) or temp >/=100.4F(38C) for at least 1hr. Initial Eval: a.
Assessment (mouth, skin, lung, UT, neuro) b. Culture (blood-2sets, urine, stool, CSF, ulcers/lesion) c. Labs (CBC w/ diff, LFT, SCr), d. Chest
X-Ray Organism: Gram (+) bacteria 60-70%(staph, strep, entero), Gram (-)(Ecoli, kleb, pseudo, enterobact, citrobact, proteus), fungal,viral
Empiric Abx choice- potential infecting org, potential infect site, antimicrob susceptibilities, import of broad spectrum, allergy, pt infect risk
Gen Principles- tx immediately! bactericidal agents, use agents effective against organisms in hosp, minimize toxicity Low risk (outpt):
ANC>100, normal CXR, normal kidney/liver, neutropenia<7days, expect resolution in 10days, no IV catheter infect, bone marrow recovery,
malignancy in remission, peak temp <39C, no mental status change, no ab pain, no comorbid complications Outpt-PO abx: i. cipro and
amox/clav (if PCN allergy, use cipro and clindamycin) ii. IVabx same as for high risk Inpatient(highrisk)- monother(3rd/4th gen) cefepime
2grams IV Q8H duel ther.- aminoglyc(gent or tobra) Plus cefepime, piper/tazo, meropenem Vanco- 10-15mg.kg/dose IV Q12h(dose adjust
renal) for infect tunnel catheter, gram(+) blood culture, HoTN/sepsis, MRSA ceph resist severe mucositis/viridians strep Antifungal-voricon,
fluconazole, caspo, lip AmphoB Antiviral-acyclovir Re-eval/modification: if afeb after 3-5days and eti known, adjust approp. If still febrile
for 3-5dys consider: cont abx, switch abx, antifungal therapy. If afeb, (-) culture, no infect site, ANC>500 for 2consec days then d/c abx.
Infection Px: handwash, minimize invasive procedures, avoid crowds, fresh fruit/veget/flowers. Decrease endogen orgs. antimicrob prophylax
NCCN pts w/ ANC<100 for >7dys. Cont. until fever absent or ANC>100. Antifungal/viral prophylax NCCN guidelines: BMTand acute
leukemia receiving non-transplant regimen Acute emesis- 1st 24hrs. of chemo. 24 hrs. after chemo-may occur up to 5-7 days after,
Anticipatory emesis specific stimuli (sights, smells, sounds), Breakthrough emesis- on the day of chemo, Refractory emesis- nausea on
previous cycles of chemo Reasons-gi- gastric outlet obstruction, gastroparesis, bowel obstruction, constipation, hepatic metastases :neurologicsevere chronic pain, anticipatory, metastases, vestibular dysfunction, incr. intracranial press:metabolic-hyperca, hypergly, hypoadrenalism,
hypona, uremia:drugs-opiods, digoxin, chemo., anesthetics, ethanol:psychophysiologic-anxiety, anticipatory n/v. vomiting center-located in
lateral reticular formation of medulla, activation leads to efferent transmission to salivary, vasomotor, respiratory centers, and to cranial nerves
VIII and X. Indirect activation of vomiting center: cerebral cortex, hypothalamus, thalamus, vestibular apparatus, peripheral visceral vagal
afferents:Chemo trigger zone-most drugs act here, located in the area postrema of the brain, located outside the blood brain barrier, accessible
to either blood or CSF borne toxic stimulus, transmits signals to vomiting center using serotonin or dopamine, may be stimulated by chemo
agents, dig, opiods, anesthetics: CTZ and vomiting center send efferent transmissions to effector organs (abdominal muscles, diaphragm,
stomach, and esophagus) to coordinate expulsion of stomach contents, stimulation of neurokinin 1, 5HT3, D2, H1, norepinephrine,
apomorphine, neurotensin, angiotensin2, vasopressin, opiate and or substance P receptors start emetic process: Complications-dehydration,
electrolyte imbalance (Na, K, Cl), acid/base disturbance (pH and CO2), malnutrition, aspiration, pneumonia, mallory-weiss syndrome,
prolonged hospitalizations, diminished QOL: Risk-female, motion sickness, pregnancy, prior chemo experience, age <30 or >60 incr. risk of
extrapyramidal side effects, anxiety, alcohol intake (>100 gm/d), type of chemo, Emeto-identify one or more level 2 agents incr. the
emetogenicity by one level greater than the most emetogenic agent in the combination, adding level 3 or 4 agents incr. the emetogenicity of the
combination by one level per agent: so 2+2=3, 2+2+2=3, 3+2=4, 3+2+2=4, 3+3+3=5: Goals -achieve complete control in all settings, provide
maximum convenience for patients and staff, eliminate potential side effects, minimize $ and drug admin, Serotonin recep antag: dolasetron
100mg po/iv 7.5hrs half life, ondansetron 8-16mg po/iv 4 hrs (these given 1 dose prior to chemo to prevent n/v), palonosetron 0.25mg iv only
128 hl (given 1 dose Q5days): MOA-direct selective antagonism of serotonin receptor sites, blocked in two ways, peripheral-enterochromaffin
cells in gi tract, central-medulla (vomiting center), ADR-HA, constipation/diarrhea, somnolence, dizziness, serotonin syndrome, asymptomatic
and transient EKG abnormalities, elevated transaminases: Cortico-decadron 8-20mg po/iv pre chemo, delayed n/v-4mg po/iv Q68H,
mechanism- inhibition of prostaglandin synthesis in cortex, decr. Serotonin turnover in CNS, modulation of higher cortical pathways that head
to the vomiting center, ADR-hypergly, fluid retention, HTN, electrolyte imbalance, euphoria, insomnia, anxiety, incr. appetite, immunosupp:
Neurokinin1 antagonists-aprepitant, MOA-blocks substance p in brainstem vomiting center and gi tract, drug interactions (CYP3A4,
CYP2C9), given 3 days per cycle, when administered >14 days=inducer, select agents metabolized by CYP3A4-docetaxel, etoposide,
ifosfamide, irinotecan, imatinib, paclitaxel, vinblastine, vincristine, vinorelbine, oral contraceptives, warfarin, dexamethasone,
midazolam:CYP3A4 inhibitors like macrolides, azoles, may increase aprepitant AUC, CYP3A4 inducers may decr. AUC, ADR-astehnia/
fatigue, dizziness, hiccups, gastritis, heartburn, diarrhea, incr. LFTs (mild/transient): Phenothiazines- compazine 5-10mg po/iv Q46HPRN,
phenergan 12.5-25mg po/iv Q6HPRN, MOA-dopamine receptor antagonists (CTZ is target), ADR-EPS (anxiety, tremors, restlessness),
excessive sedation, hypotension, liver dysfunction, bone marrow aplasia: Butyrophenones- haldol 0.5mg po/iv Q46HPRN mechanism-DA
receptor antagonist (CTZ is target), ADR-EPS, sedation, anticholinergic, torsades:Benzamide analogs-reglan 10mg po/iv Q6HPRN, tigan
300mg po Q6HPRN, mechanism-DA and 5HT receptor antagonists, enhances response to Ach of tissue in upper gi tract causing enhanced
motility and accelerated gastric emptying, ADR-sedation, confusion, EPS, diarrhea, edema:Cannabinoids-dronabinol 2.5 mg po BID (titrate
up to maximum 20 mg/day), mechanism-may inhibit endorphins in the vomiting center, suppress pg synthesis, or inhibit medullary activity
through an unspecified cortical action, ADR -drowsiness, dizziness, euphoria, dysphoria, mood changes, orthostatic hypotension, ataxia,
hallucinations, time disorientation, incr. appetite:Benzo- ativan .5-2mg iv/po Q46H, causes antegrade amnesia, decr. no activity as antiemetic,
ADR -sedation, hypotension, hallucinations, urinary incontinence, motor incoordination:Antihistamine- meclizine 12.5-50mg po Q12H,
mechanism-cental anticholinergic action by blocking CTZ, ADR -slight to mod drowsiness, HA, thickening of bronchial secretions: Belladona
Alkaloid-scopolamine (apply 1 patch behind ear every 3 days, mechanism-blocking Ach receptors in the vestibular apparatus, ADR -dry mouth,
sedation, impaired eye accommodation, Non-drug therapy-relaxation, guided imagery, desensitization, hypnosis, acupuncture: prevention of
CINV-evaluate pt individually, evaluate chemo regimen, most effective when give px, flexibility-you may need to change therapy daily or with
each cycle, PO and iv have equal efficacy, Guidelines for Px:levels 4 and 5 start 30 min prior to chemo on day 1. give aprepitant, serotonin
receptor antagonist, decadron: aprepitant-acute 125mg po on day 1 pre-chemo, then 80 mg po on days 2,3 and serotonin receptor antagonist
acute 100mg po or iv on day 1 and decadron 12mg po or iv on day 1, then 8 mg po or iv on days 2, 4. for delayed compazine 10mg po
Q4HPRN. For level 3 regimens use the exact same treatment as level 4,5 except only use aprepitant in a select group of patients! Level
2-decadron 8mg po/iv x1 and compazine 10mg po/iv Q46HPRN, level 1 regimen-none unless they have a history of n/v. delayed n/v use
compazine 10mg Q4HPRN, anticipatory-benzodiazepines and non-drug therapy, motion=antihistamine or belladonna
Drug
Morphine
Codeine
Oxycodone
Dilaudid
Hydromorph
Meperidine
Methadone
Route
IM
PO
IM
PO
PO
IM
PO
IM
PO
IM
PO
Equiv. Dose
10
30
130
300
30
1.5
7.5
75
300
10
20
Duration
4
4
4
4
3-5
4
4
4 (2?)
4 (2?)
6-8
6-8
Plasma T½
2-3.5
Duration
Acute
Hours/Days
Chronic Malig
Months/Years
Chronic Non
Unpredictable
3
Pathology
Present
Usually
Not common
?
2-3
Bio Value
Psych Effects
High,until none
Uncommon
Low
Yes
Low/None
Yes
3-4*
*normerperidine
12-24
Social Effects
Minimal
Varies, marked
Profound
Treatment
Analgesics
Pharm, other
modal
Multimodal, phys
/behav., Pharm
Ovarian: 63 (post-menopausal), lifetime risk 1.7%, white ETIO: “Incessant Ovulation” y—# of ovulation cycles disruption and repair of
lining of ovary; Tumor supp genes BRCA1(25-45%risk), 2(27%),&p53 5-10% cases; Hereditary non-polyposis colorectal cancer (HNPCC)
(Lynch II) role in 5-10%RISK: Inc: early menarch(<12) late menopause (>55), (0 pregnancies), inc. age, first kid >35, white, n.american, north
europe, genetic, controversials—HRT, environmental, diet, ovulatory stim. drugs, Decreased: BOC(>5yrs) dec by 50%, >1 full term pregnancy,
breast-feeding, oophorectemy, tubal ligation , Genetic: # of first degree relatives w/disease, Familial—5% if 1 1st degree relative, 7% if 2 1st
degree; F at high risk(hered, BRCA1, BRCA2 positive)—pelvic exam, transvag. Ultrasound, CA-125 starting at age 25-35 (CA-125 <
35unitls/ml) P: oral conc., oophorectemy PATH: Epithial adenocarcinoma 90% cases, on surface of ovaries, histopathologic
subtypes(serous-most common, mucinous, endometriod, clear-cell, Brenner), grade 1- grandular and well differentiated tumors(better
prognosis), grade 2 – tumors w/grandular and solid areas, grade 3 – solid and poorly differentiated tumors; Sex cord-stromal tumors(hormone
producing) grandulosa tumor; Germ-cell tumors(aggressive) age 15-25yo, >90%survival at 5yrs, includes dysgerminoma, malignant teratoma,
embryonal carcinoma; Metastatic breast/colon SIGNS/SX: ab pain, change in bowel or bladder fx, bloating, vag bleedingGI-n/v/dyspepsia,
diff. eating, pulm. SOB, ascites w/ poss. abd distention, pelvic mass, highCA-125DIAG: hx/physical, ab/pelvic pain, CA-125 (elevated in
85%), transvag ultrasound, imaging ovaries &abdomin—ultrasound, CT, MRI, colonoscopy or barium enema, chest xray, CBCs, LFTs,
chemistryFIGO STAGING: (given) Stage 1(T1) mild –limited to ovaries, Stage 2—involves 1 or both ovaries w/pelvic extention, Stage
3(most dx)-involves one or both ovaries w/microscopically confirmed peritoneal metastasis and/or outside the pelvis and/or regional lymph
node metastasis, superficial liver metastasis, tumor limited to pelvis but malignant extention to small bowel or omentum, Stage 4(M1) –growth
involving 1 or more ovaries w/distant metastasis, parenchymal liver metastasis equal stage 4 disease, pleural effusion must have positive
etiology for designation of stage 4MANAGEMENT: Surgery—cure/treatment; Chemo—cure/treatment; Radiation; HRT INITIAL TX:
Stage 1comprehensive surgical staging for all pts., includes total abdominal hysterectomy(TAH), bilateral-salpingo-oophorectemy(BSO),
complete abdominal exploration, intact tumor removal; possible pelvic and para-aortic lymph node sampling, appendectomy, omentectomy,
perotineal biopsies, cytologic washings; unilateral salpingo-oophorectemy if stage 1A and pt desires fertility, must be done by gynecologic
oncologist for accurate staging; If early stage, favorable features, and 1A/1B=only surgical staging; If unfavorable, grade 2 or 3, or 1C =
Paclitaxel 175mg/m2 IV over 3h on day 1 & Carboplatin (AUC5-7) IV on day 1 given q21days for total of 6 cycles Stage 2,3,4
comprehensive surgical staging w/chemo, Preferred: Taxane(paclitaxel or docetaxel) + Platinum compound(carboplatin or cisplatin) for 6
cycles; Stage 3C or pts w/minimal residual disease (2cm) consider intraperotineal chemo w/ paclitaxel 135mg/m2 IV on day 1 + cisplatin
100mg/m2 IP on day 2 + paclitaxel 60mg/m2 IP on day 8 + neulasta; Extent of surgery—optimal cytoreduction (<1-2cm residual disease at end
of surgery), sub-optimal (>2cm residual disease) Select Patients neoadjuvant chemo (prior to surgery) if pt. medically inoperable initially;
secondary cytoreduction if initial surgery leaves sub-optimal disease start chemo 2-3 cycles followed by surgery again Monitoring Primary:
pelvic exam q2 cycles, CA-125 prior to each cycle, CBC’s, platelets, chemistries, imaging if necessary; End of 6 cycles: complete pelvic/PE,
CA-125 q 2-4 months for 2 years, then q6months for 3 years, then annually, imaging only in highly select patients TX RECURRENT: (6080% relapse), no standard therapy, treatment/prognosis go by initial response to chemo, Platinum sensitive (remission > 6 months) –first
recurrence use Carbo + Pac, Carbo, Cis, Pac, Gemcitabine + Carbo; use other agents for subsequent; Platinum resistant (< 6 months remission)
—salvage agents; use liposomal doxorubicin, topotecan, docetaxel, gemcitibine, bevacizumab, altretamine; Primary progressive(platinum
refractory)—clinical trial agents PROGNOSTIC FACTORS: Stage(1 better than 4), vol. of residual disease at time of surgery(< 2cm),
histologic subtype & grade, CA-125 CHEMO: Taxanes: MOA: enhances polymerization of tubulin & induces formation of stabile
nonfunctional microtubules, blocks cells in late G2/M phases; Paclitaxel (Taxol®) Source: bark of pacific yew Dose: 175-225mg/m2/3weeks
(3h) or 135mg/m2/3weeks (24h) Drug Int: Cyp450 Dose Adjust: Hepatic Premedications: Decadron 20mg po 12 & 6 hours prior to paclitaxel,
decadron 20mg, diphenhydramine 50mgIV, famotidine20mg 30 min. prior to paclitaxel (cremophor) Toxicity: hypersens(flushing, bone pain,
rash), hypotension, brady, neutropenia, peripheral neuro(3h), arth/myalgia, mild inc. LFTs, alopecia Docetaxel(Taxotere®) Dose: 750100mg/m2/3weeks (1h infusion) DI’s: Cyp450 Dose Adjust: hepatic Premeds: Decadron 8mg po bidx3-5days Toxicity: neutropenia, fluid
retent, skin/nail toxic, alopecia, neurotoxic, myalgia, asthenia; Platinum analogues: MOA: aquation reaction w/H20 replacing Cl- groups to
form +charged, reactive, electrophiles, active platinum species reacts w/DNA, covalent binding of platinum to DNA forms intra- inter-strand
cross links Mechanism of resistence: reduced cellular drug accumulation, cytosolic inactivation of drug, DNA repair enhancement
Cisplatin(Platinol®) Dose: 20-100mg/m2 IV, IP Toxicity: nephrotoxic(prevent w/ aggressive hydration, mannitol), n/v (acute/delayed),
neurotoxic, ototoxic(peds), peripheral neuropathy, mild myelosuppression(good), e- abnorms dec Mg, K, Carboplatin(Paraplatin®) Dose:
Calvert Formulamyelosupression (thrombocytopenia mainly, dose-limiting, neutro and anemia poss), n/v, hypersens.(>7cycles or hx)
Desensitization: if sens. to Cisplatin, give Carbo 1:1000, 1:100, 1:10, 1:1 Oxaliplatin(Eloxatin®) Dose: 85-135mg/m2 Toxicity: acute
neurotoxicity (w/in hours, avoid cold for 5 days, laryngopharyngeal spasm, infustion rate dependent), delayed sensory neuropathy(cumulative)
Topotecan(Hycamtin®) MOA: topoisomerase inhibitor results in DNA single strand breaks Dose: 1.5mg/m2 IV dailyx5daysq21days or
IVqweekx3weeks w/1 week off Elimination: renal Toxicity: neutropenic, alopecia, low-grade fever, n/v/d, rash, transient hepatic transaminitis
Liposomal doxorubicin(Doxil®) MOA: intercalates b/w base pairs inhibiting DNA syn & DNA dependent RNA syn, inhibits protein synthesis,
encapsulation improves therapeutic index & selective delivery of drug to tumor Dose: 40-50mg/m2 IV q3-4weeks Dose Adjust: impaired
hepatic func, modify if pt has hand-foot syndrome, stomatitis, hematologic toxic Toxicity: less cardiac tox. than normal doxorubicin, hand-foot
syndrome, myelosuppression, mucositis, mild n/v, acute infusion reaction(chills, fever, flushing) Gemcitabine(Gemzar®) MOA: antimetabolite,
inhibits DNA polymerase and ribonucleotide reductase, specific for S-phase Dose: 1000mg/m2 IV once weekly x3weeks, repeat cycle q4weeks
Toxicity: myelosuppression(dose limiting: all 3), fever, rash, alopecia, dyspnea, n/v/d, inc LFTs Bevacizumab(Avastin®): MOA: inhibits
vascular endothelial growth factor, recombinant humanized monoclonal IgG1 Dose: 5-15mg/kg IV q2-3weeks, wait 28 days post surgery,
Administration: 90 min infuse, then 60, then 30 if tolerated, T1/2 ~20days Toxicity: HTN, proteinuria, DVTorPE, would healing, hemorrhage,
GI perf PAIN- Prev – Newly diag (28%), Active tx (50-70%), Adv. Disease (64-80%), >80% before dying- Uncontrolled– (1) disturb normal
coping/adjustment; augment vulnerability, cause risk for catastrophic outcomes; (2) mood /beliefs ab/ meaning of pain; exacerbate perceived
intensity & pain is a maj. factor in function/mood PAIN – unpleasant sensory/emotional experience assoc. w/ actual/potential tissue
damage/described in terms like damage- Etiology –1/metastatic dx; develop pain to 1) surgery 2) radiation 3) chemo 4) (osteo, immob., infect.)
Acute = several days, intermittent/ confined time & unpredictable; <3 mos., Ex: bone marrow biopsy, post op, chemo, WBC GF, bone pain
Chronic-persistent cancer >3 mos, pain caused by dx (HIV, MS, ES organ failure), Ex: bone metastasis, nerve pain, post chemo, peripheral
neuro., tumor infiltration Chronic non-malig-myofascial, neuropathic, complex regional, failed back, H/A, arthritis UNDERTX-ped/geriatric
pt, communication, substance abuse, neuro pain, minorities, females, culture-Risks of Unrelieved - catabolic demands, RR, limb move
(clot risk),GI motility,Na/water retention, tachycardia,BP, infection ,negative emotion, sleep, suffering- Onset, Location, Duration,
Characteristics, Aggravating, Remitting, Temporal, Severity-Universal Screening-pain=0 (reassess later), pain>0(assess)
A=Ask,Assess,B=Believe,C=Choose,D=Deliver E=Empower ACUTE -prevent, sched. analgesics, PRN breakthrough -mildNSAID,
modlow-dose opoid+NSAID, severehigher opiod+NSAIDs (elevate opiods as needed, + adjuvants)-consider PCA (6-8 min), epidurals,
nonpharm -general approach to tx-by mouth(pills), by clock by ladder , for individual, reassess frequently, balance pain relief and Ses Mild(13) no ASA -APAP=antipyretic, hepatotoxic, ≤4g, ceiling effect -NSAIDs=ceiling effect, antipyretic, antiPLT, renal/GI tox,LFTs Mod (4-6)start mild opiod -Codeine-limited N/C/allergy, dn exceed 1.5mg/kg b/c SEs -Hydrocodone- limited by APAP effect Severe(7-10)-start
strong opiod-Morphine-standard use, caution renal dysfunction, N/V Hydromorphone-potency,caution in liver dysfunction-Oxycodone-no
IV-Fentanyl-unique transmucosal,transdermal patch (never cut), lipophilic area, n for use in cachectic pt -Methadone-cheap,lasts 4-8hr,
t½=15-48hr, tough to titrate-Agents NOT Rec.-meperidine,agonist-antagonist(pentazocine butorphanol,denocine,nalbuphine IM erratic absorp
Salicylates
P-Aminop.
Derivatives
Propionic acids
ASA
APAP
3-12 hr
2-4 hr
325mg PO q6h
325-650mg PO q6h
Ibu
Naproxen
Nap Na
Ketorolac
PO(15,30,60)
PO(5/325,5/
500,7.5/500,
10/650)
PO 100,
100/650
Many
1.8-2 hr
13 hr
13 hr
4-7hr
15-120 q4
2.5-10 q4
max-60qd
200-800 PO q6h
250-500 PO q12h
220-550 PO q12h
15-30mg IV q6h
2-3
3-4
N/C
2-3
3-4
w/ APAP and
ASA
100 Q4
Max600qd
10-30 q4 and 1-4
IV q3-4
2-3
3-4
n routine use
2-3
3-4
Concent. Oral
soln
(20mg/ml)
Hmorphone
2 mg 4 mg
Oxycodone
5,15,30 mg
Fentanyl
Many
2-3
3-4
Tab, liquid
2-4 q4 and 0.2-0.6
IV q 3-4
2.5-10 q4
2-3
3-4
see morphine
IV,
Transmuc
25-100 IV q 1-2
and 200 TM start
1-2
1-3
1-2
Tramadol
Tab
50-100 q4-6
Max400qd
~6
9
Mcg,
breakthrough,
F=0.5(buccal/
Oral)
CNS
Acetic Acid
Codeine
Hmorphone/
APAP
Propoxy.
Nap
Morphine
Opiate SEs-CONSTIPATION-tolerance dn develop, need fluids/
fiber/exercise, prophylaxis-docusate+senna (w/opoid), pharm-inc lax,
PRN MOM, biscodyl,lactulose, sorbitol,mag cit,enemas NAUSEA-PRN
(prochlorperazine), SEDATION-dose related, dose/frequency,
methylphenidate RESP-  w/ increasing doses URINARY
RETENTION/BLADDER SPASMS- elderly, dose PRURITIS(Benadryl)SEIZURES- only with high doses - opoids no ceiling effect titrate up w/ inadeq relief, failure, breakthrough (≥3 PRN daily x 2-3d) total opoid (ATC+PRN) depending on pain scale; 50-100% for severe, 2550% for mod, 25% for mild -PRN should be 10% of daily dose, freq of
titration q12-24h for chronic/oral opoids, q1-4h for acute/crisis/parenteral down titrate w/ no SEs/no pain, dec. pain source, no PRNs -down titrate
50% x 2d, 25% q 2d until preferred dose/no pain medication needed (can
vary, gradual 1-7d, rapid 50-75% q12-24h) bone metastasis-bisphosphanates
(pamidronate 60-90 IV q mo or zoledronic acid 4mg IV q mo), NSAIDs,
Corticosteroids (dexamethasone), radiation, radiopharm (strom-89, sumar153)NEUROPATHIC-opiates, TCAs (amitrtiptylline), SSRIs (duloxetine
60mg BID, max 300/d), Anticonvulsants (gabapentin 100mg BID/TID, max
3600/d or Pregabalin 50mg TID, max 300d), Nerve blockCONVERSION
IV Morphine to (Fentanyl)8-22mg=25mcg, 23-37= 50mcg, 38-52=75mcg,
53-67=100mcg, 68-82=125mcg, 82-97=150mcgCASE 1: 1. metastatic
melanoma to liver/lungs 2. N/V (morphine induced)- modify pain
SR Morphine
MSContin-q12, q8
8-12
Rectal MSContin good
therapy 3. cancer-related pain- MsContin, Morphine IR 2. Comp
15,30,60,100,200
for 8-12hr
10mg PO/25 PR (Mon- EPS (benadryl), excess sedation, HoTN,
Kadian(can
open)-qd,q12
12liver dysfunct, bone marrow aplasia). KW-180mg MsContin/day—
20,30,50,60,120
24
switch to Duragesic 50mcg/hr 1 patch Q72hrs (mon-n/v, resp
SR Oxycodone, Oxycontin-q8h, q12h
12
depression, sedation, bp, don’t cut, no heat on patch, fatty area
Oxycontin
10,20,40,80,160
absorb better). [OR switch to Oxycontin 180mg/day x 0.75
Transderm Fent Duragesic- q72h
72
Skin depot, 48 h in
12mcg/hr,25,50,75,100
some
135mg/day => oxycontin 40mg Q8hr.] KW also take 90mg
Methadone
Dolophene- tab-5,10mg
6-8
Long t½ , cheap, long
morphine IR/day – 90/x=30/1.5 => Dilaudid 4.5mg IV x 0.75 =
Q6 Q8
soln 1mg/ml, 10mg/ml
3.4mg/24hr =>0.14mg/hr cont infusion => dilaudid 0.56mg IV
Levorphanol
Oral: 2-4mg PO q6-8h PRN 6-8
Long t½ , refract N/V
Q4hr prn (PO usage 90/x=30/7.5 => 22.5mg PO x 0.75 =
IV: 1-2mg IV q6-8hr PRN
16.9mg/24hr =>dilaudid 2.8mg PO Q4H prn). If tolerated inc
dilaudid dose to 28mg/24hr (22.5mg x 1.25) => 4.7mg PO Q4hr prn (mon- pain relief, resp/ment status, weakness, n/v/constipation)Case
2A(CrCl 74.5/1.92 m2) 1.Stage IIA Carboplatin(4) + Paclitaxel(2) 2.Mild (3/10) PN- Paclitaxel ADR determine Tx 3. N/V Px (5)- Palon ;
Loraze; Dexa 4. Hx of abnormal pap smears- determine Tx 5. Anxiety- Sertraline 6. HTN- determine Tx 7. Dyslipid- Pravastatin 2.Switch to
Paclitaxel 135mg/m2/3wks/24 hours (less PN, mon: myelosuppression) + Add Gabapentin 100 mg TID- titrate to 300mg TID (mon sedation) 4.
screen for cervical cancer 6. monitor BP **Monitor: pelvic exam Q2 cycles; CA-125 before each cycle; CBC; platelets End of 6 cycles: pelvic
exam and CA-125 Q2-4 mos for 2 yrs then Q6 mos for 3 yrs then Qyr. 2B (plat sensitive): 1. Stage IIIC -determine Tx 2. Anemia-11 gm/dL 3.
Anxiety-Sertraline 1. Carboplatin + Pacletaxel (same dose, mon PN and neutropenia) N/V Px? 2. Consider Epoetin Alfa 40,000 U/wk mon: bp,
Hgb/Hct.Case 3 (CrCl 142.03/2.1 m2): 1.relapsed non-hodgkins lymphoma- ESHAP + Ritux 2. N/V Px level 5- (risk-Hx of motion sickness)
determine Tx 3. Anemic-12 gm/dL- determine Tx 4.Depression- paroxetine 5. GERD- pantoprazole 2. N/V px:dolestron 100 mg IV on Day 1
(30 mins prior to chemo) (mon: HA, constipation, somnolence, dizziness, serotonin syn) Methylpredn 500 mg IV Day 1 (30 mins prior)
Continue Days 2-5 (mon: sugar, bp, electrolytes, mood, wt) Meclizine 12.5 mg PO Q12PRN (mon: drowsy, HA) Delayed: Comp 10 mg (mon:
sedation, EPS, hypotn, BM, LFTs) Nonpharm: Relaxation, Guided Imagery, Densenstization, Hypnosis, Acupuncture 3. Mon Hgb/Hct Case 4:
1. recurrent invasive breast cancer- metastatic to bone 2. somatic (aching, throbbing) severe pain (7/10)- inadequate therapy - naproxen +
oxycodone ATC 3. thrombocytopenia – 80K determine tx. 4. anemia – HgB-12 –determine tx. 5. depress – escitalopram. 6. nutrition– MVI*No morphine* D/C NSAID (min pain relief potential, antiplatelet effect). Since pain 7/10, increase dose by 50-100%. Long-acting—
Oxycontin 20mg PO Q12hr also incr. interval of BTP med. to oxycodone IR 5mg PO Q4hr pp (mon- pain relief, resp/ment status, bp,
n/v/constipation, pruitis). Zoledronic acid 4mg IV mos (monitor: edema, HoTN, fatigue, fever, risk of jaw osteonecrosis, renal function,
electrolyte levels). thrombocytopenia- d/c NSAID. monitor plt until nadir. If plt count <50K, then consider Oprelvekin 50mcg/kg SC daily
initiated 24hrs after chemo completion and cont 14-21days(max 21days) or plt count >50K. Many ADEs (cardiac, resp, edema, SOB, h/a, dizzy,
thrombosis, myalgias)Case 5: Part 1- 1.AML – Idarubicin, Cytarabine. 2. Risk for TLS – (increase LDH, UA, blasts) determine treatment. 3.
N/V px – deter tx. 4. anemia – HgB 9.2 5. heartburn – famotidine. 6. seasonal allergies- fexofenadine. TLS? rapid tumor cell lysis, releasing
UA, K, Phos into blood which exceeds ability of norm compensatory mechs. At risk? hematologic malignancies (leukemia/lymphoma), tumors
w/ high proliferative rates, large tumor burden, preexist renal insuff. TLS. – increased K, P, UA, Cr, LDH, wt. dec Ca, urine output. Pxof
TLS- hydration-start 24-48hrs prior to tx (goal output >100mL/hr), alkalize urine-IV fluids +NaHCO3 goal urine pH >7 or acetazolamide,
allopurinol 300mg PO QD start 24-48hr before chemo, rasburicase 3mg IV x 1as tx of TLS. N/V px(4) – aprepitant: 125mg on day 1, 80mg
PO on day 2-3 (monitor fatigue, dizzy, hiccups, diarrhea), dolasetron 100mg PO/IV on day1, dexa 12mg PO/IV on day1, 8mg PO/IV days
2-4 tx Comp 10mg PO Q4-6H PRN Part2: 1. AML –day11of 1st chemo cycle. 2. neutropenic fever – determine tx. 3. thrombocytopenia. 4.
anemia. 5. seasonal allergies. 6. heartburn. 7. Mild H/A – oxycodone/APAP ANC= 98. Cefepime 2gm IV Q8H until ANC>/=500cell/mm3
for 2 consecutive days, afebrile, negative cultures, no definite site of infection (monitor: hypersensitivity, rash, GI, negative cultures, h/a)
(alternative; aminoglycoside + cefepime, or vanco 10-15mg/kg/dose IV Q12H) handwashing, minimize invasive proced, avoid crowds, fresh
fruit. Consider antimicro/antifun/ antiviral px. Would filgrastim? No b/c of active leukemia. potential benefit once pt is in remission. Mild
H/A – d/c percocet. Tramadol 50mg Q4-6H PRN H/A. (Monitor: pain relief, resp rate, bp, tolerance, cns effects, n/constipation)