Download The Side Effect Profile of Carfilzomib

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The Side Effect Profile of Carfilzomib:
From Clinical Trials to Clinical Practice
LAURA McBRIDE, RN, BSN, OCN®, CCRP, and CHRISTINE O. SAMUEL, RN, BSN, OCN®, CCRP
From John Theurer Cancer Center at Hackensack University Medical Center, Hackensack,
New Jersey, and MD Anderson Cancer Center,
Houston, Texas
Authors' disclosures of potential conflicts of
interest are found at the end of this article.
Correspondence to: Christine O. Samuel, RN,
BSN, OCN®, CCRP, Lymphoma/Myeloma Center,
MD Anderson Cancer Center, 1515 Holcombe
Boulevard, Houston, TX 77030.
E-mail: [email protected]
© 2013 Harborside Press®
Abstract
Treatment of patients with relapsed and/or refractory multiple myeloma
(RR MM) is challenging due to the heterogeneity of the disease, patient
comorbidities, and side effects of individual treatments. Carfilzomib, a
selective proteasome inhibitor that has shown safety and efficacy as
a single agent in phase I and II trials, was recently approved by the US
Food and Drug Administration for RR MM. The aim of this review is
to summarize adverse events (AEs) in patients with MM treated with
single-agent carfilzomib in phase II clinical studies and to provide insight
into the prevention and management of these AEs from the perspective
of the advanced practitioner (AP). Data from a cross-trial safety analysis describing the safety and tolerability of single-agent carfilzomib in
526 patients with RR MM who received carfilzomib in four phase II trials
are summarized. Additional information is included based on AP clinical
practice experience gained in the clinical trial setting. Guidelines are suggested to assist with patient management prior to carfilzomib treatment,
including hydration and prophylactic medication, as well as the management of hematologic AEs, fatigue, and dyspnea during treatment. Infrequent but potentially serious AEs, including cardiac and renal complications, are also reviewed. Adverse events in varying frequencies occur in
response to carfilzomib, but they can be managed with prophylaxis and
routine care. Utilizing the clinical practice experience with carfilzomib
presented here should help to maximize the efficacy of carfilzomib while
minimizing AEs and potential discomfort in patients with late-stage MM.
J Adv Pract Oncol 2013;4(Suppl 1):22–30
M
ultiple myeloma (MM)
is a hematologic cancer that is expected
to result in more than
10,700 deaths in the United States in
2013 (American Cancer Society, 2013).
J Adv Pract Oncol
22
Multiple myeloma mainly manifests as hypercalcemia, renal insufficiency, anemia, and bone lesions,
mnemonically referred to as CRAB
(Raab, Podar, Breitkreutz, Richardson, & Anderson, 2009). Patients can
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SIDE EFFECT PROFILE OF CARFILZOMIB
range from asymptomatic to severely disabled, depending on where they are in the course of their
disease (Pingali et al., 2012). Although new treatments have improved outcomes for patients with
MM, the disease remains incurable and is associated with limited survival (Laubach et al., 2011;
Ludwig et al., 2011).
Along with the clinical manifestations of the
disease, it is important to be aware of the common side effects of MM treatments; these can
include myelosuppression, infection, peripheral
neuropathy (PN), thromboembolic complications, and untoward cardiac side effects (Pingali,
Haddad, & Saad, 2012). Treatment of patients
with relapsed and/or refractory (RR) MM is particularly challenging due to the heterogeneity of
the disease, patient comorbidities, complications
caused by the disease, and the adverse events
(AEs) associated with individual treatments
(Dimopoulos & Terpos, 2010; Laubach et al., 2011;
Mohty et al., 2012; van de Donk et al., 2011).
Carfilzomib (Kyprolis) is a proteasome inhibitor that has shown safety and efficacy in patients
with RR MM in both phase I (Alsina et al., 2012;
O’Connor et al., 2009) and phase II trials (Badros
et al., 2013; Jagannath et al., 2012; Siegel et al., 2012;
Vij et al., 2012a, 2012b). Carfilzomib selectively
and irreversibly inhibits the chymotrypsin-like
activities of both the constitutive proteasome and
the immunoproteasome via a binding mechanism
that is distinct from that of the reversible inhibitor
bortezomib (Velcade; Arastu-Kapur et al., 2011).
Carfilzomib has a short half-life (Badros et al.,
2013; O’Connor et al., 2009), which, along with its
selective binding and lack of off-target effects, may
explain the favorable safety profile of the drug.
Carfilzomib was recently approved by the US
Food and Drug Administration (FDA) for patients
with RR MM. Approval was based on results from
the pivotal PX-171-003-A1 trial (ClinicalTrials.gov
identifier NCT00511238) for efficacy and safety
and studies PX-171-003-A0 (NCT00511238),
PX-171-004 (NCT00530816), and PX-171-005
(NCT00721734) for safety (Onyx Pharmaceuticals,
2012; Siegel et al., 2012, 2013).
To maximize the benefits of carfilzomib, it is
important to understand the possible AEs associated
with its administration. The objective of this review is
to summarize both common and infrequent clinically
relevant AEs observed following carfilzomib use
and to provide insight into the management of
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REVIEW
these events from an advanced practitioner (AP)
perspective, based on clinical experience in the phase
II trial setting as well as current use.
ADVERSE EVENTS IN CLINICAL
TRIALS AND CLINICAL PRACTICE
A cross-trial safety analysis has been reported
describing the safety and tolerability of single-agent
carfilzomib in 526 patients with RR MM who received
carfilzomib in four phase II trials: PX-171-003-A0,
PX-171-003-A1, PX-171-004, and PX-171-005 (Harvey et al., 2012; Lonial, Niesvizky, McCulloch, Rajangam, & Vij, 2012; Martin et al., 2012; Nooka et al.,
2012; Siegel et al., 2013). The most common hematologic AEs were anemia and thrombocytopenia,
while the most common nonhematologic AEs were
fatigue, nausea, dyspnea, diarrhea, pyrexia, and upper respiratory tract infections; see Table 1 (Onyx
Pharmaceuticals, 2012; Siegel et al., 2013). The most
common events ≥ grade 3 were mainly hematologic
and included thrombocytopenia (23.4%), anemia
(22.4%), lymphopenia (18.1%), pneumonia (10.5%),
and neutropenia (10.3%). Of the 526 patients in this
analysis, 14.6% required a dose modification and
14.8% discontinued treatment due to an AE (Siegel
et al., 2013).
Adverse events frequently observed in the
clinical setting can be found in Table 2, listed
according to relative observed frequency; these
events are generally consistent with those reported
from the clinical trials noted above. Adverse events
most commonly appearing in the first 24 to 48
hours include infusion-related reactions characterized by flu-like symptoms including fever, rigor,
chills, and dyspnea; injection site–related reactions
such as phlebitis; increases in certain laboratory
values (including creatinine and transaminases);
and elevations in blood pressure. Other common AEs that can appear either early or in later
treatment cycles include fatigue, gastrointestinal
AEs, hematologic AEs, dyspnea not related to initial
dosing, infections, and similar increases in laboratory values described above. Cardiac, renal, and
hepatic AEs are reported infrequently but can lead
to serious complications.
RISK MANAGEMENT
Baseline Assessment
It is well-accepted that patient education is
an important tool that can improve treatment.
In order to obtain a thorough baseline profile of
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McBRIDE and SAMUEL
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Table 1. Incidence of Treatment-Emergent Adverse Events in > 10% of Patients From 526 Patients in
Four Phase II Clinical Trials
Patients, N = 526
Event
All grades
 Grade 3
Grade 4
Anemia
246 (46.8%)
111 (21.1%)
 7 (1.3%)
Thrombocytopenia
191 (36.3%)
 69 (13.1%)
54 (10.3%)
Lymphopenia
126 (24.0%)
 84 (16.0%)
11 (2.1%)
Neutropenia
109 (20.7%)
 50 (9.5%)
 4 (0.8%)
Leukopenia
 71 (13.5%)
 27 (5.1%)
 1 (0.2%)
Fatigue
292 (55.5%)
 38 (7.2%)
 2 (0.4%)
Nausea
236 (44.9%)
  7 (1.3%)
 0
Dyspnea
182 (34.6%)
 25 (4.8%)
 1 (0.2%)a
Diarrhea
172 (32.7%)
  4 (0.8%)
 1 (0.2%)
Pyrexia
160 (30.4%)
  7 (1.3%)
 2 (0.4%)
Upper respiratory tract infection
149 (28.3%)
 17 (3.2%)
 0
Headache
145 (27.6%)
  7 (1.3%)
 0
Cough
137 (26.0%)
  1 (0.2%)
 0
Blood creatinine increased
127 (24.1%)
 13 (2.5%)
 1 (0.2%)
Edema peripheral
126 (24.0%)
  3 (0.6%)
 0
Vomiting
117 (22.2%)
  5 (1.0%)
 0
Constipation
110 (20.9%)
  1 (0.2%)
 0
Insomnia
 94 (17.9%)
  0
 0
Chills
 84 (16.0%)
  1 (0.2%)
 0
Arthralgia
 83 (15.8%)
  7 (1.3%)
 0
Muscle spasms
 76 (14.4%)
  2 (0.4%)
 0 
Hypertension
 75 (14.3%)
 15 (2.9%)
 2 (0.4%)
Hypokalemia
 72 (13.7%)
 14 (2.7%)
 3 (0.6%)
Hypomagnesemia
 71 (13.5%)
  2 (0.4%)
 0
Pain in extremity
 70 (13.3%)
  7 (1.3%)
 0
Pneumonia
 67 (12.7%)
 52 (9.9%)
 3 (0.6%)a
Aspartate aminotransferase increased
 66 (12.5%)
 15 (2.9%)
 1 (0.2%)
Dizziness
 66 (12.5%)
  5 (1.0%)
 1 (0.2%)
Hypoesthesia
 64 (12.2%)
  3 (0.6%)
 0
Hypophosphatemia
 55 (10.5%)
 24 (4.6%)
 3 (0.6%)
Hyponatremia
 54 (10.3%)
 31 (5.9%)
 3 (0.6%)
Hematologic
Nonhematologic
Note. Information adapted from Onyx Pharmaceuticals (2012).
a
One event was of grade 5 severity.
the patient, it is helpful to educate the patient
on how to provide an adequate medical history.
Particularly in individuals who are older and
J Adv Pract Oncol
have been exposed to multiple therapies, such
as those patients with RR MM, it is important
to consider comorbid conditions and to have a
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SIDE EFFECT PROFILE OF CARFILZOMIB
thorough knowledge of the patient’s medical
history. Performing a complete initial assessment
is necessary to establish a baseline profile. In all
patients with MM, baseline evaluation of cardiac
and renal function is essential. Given that PN can
be associated with treatment of MM (Mohty et
al., 2010), a baseline neuropathy examination is
important as well. However, neuropathy is not a
significant concern with carfilzomib treatment
(Martin et al., 2012). It is necessary to obtain baseline
vital signs and monitor for changes during and
after dosing, particularly in patients with a history
of hypertension. A thorough review of previous
and current medications is essential, especially for
patients with a history of cardiovascular disease.
During this initial evaluation, patients should be
advised that concomitant medication records
need to be updated frequently in order to properly
anticipate and manage potential AEs. Additionally,
a patient’s weight should be recorded at baseline
and at least once weekly during treatment.
It is important to educate the patient on the
need for prophylactic medication (which may
vary according to the patient) to help manage
AEs. It is also helpful to educate both patients and
caregivers on the side effects that may occur with
carfilzomib treatment, making sure they are aware
of what should be reported and when to report it.
Empowering patients and their caregivers with
this knowledge will enable APs to manage patients
who are taking carfilzomib more effectively.
Table 2. Relative Observed Frequency of
Adverse Events Associated With Carfilzomib
Frequently observed
• Fatigue
• Dyspnea
• Hematologic AEs
† Thrombocytopenia
† Anemia
† Neutropenia
• Upper respiratory tract infections and pneumonia
Occasionally observed
• Gastrointestinal
† Nausea
† Diarrhea
• Flu-like infusion-related reactions
• Other infusion-related complications
(e.g., site reactions)
• Increases in laboratory values or blood pressure
• Electrolyte imbalances
• Other infections (e.g., urinary tract infections)
Infrequently observed
• Peripheral neuropathy
Infrequently observed but potentially serious
• Cardiac
• Renal
• Hepatic
The carfilzomib prescribing information dosing guidelines recommend that patients receive
250 to 500 mL of normal saline or other appropriate intravenous (IV) fluid prior to the administration of carfilzomib and the same amount following
administration, as needed (Onyx Pharmaceuticals,
2012). In clinical practice, following cycle 1, patients
have been instructed to drink 8 cups of water prior
to each dose of carfilzomib in order to prevent or
reduce fatigue as well as to reduce the risk of other
potential AEs, including renal toxicity and tumor
lysis syndrome. It is, however, important to maintain homeostatic fluid balance; some patients may
require a reduction in hydration or the addition of
diuretics if they have signs or symptoms of fluid
overload, including weight gain. It is also important
to note that shortness of breath can be related to
fluid retention. If hydration is needed post cycle 1
it can be reduced as necessary. Patients at high risk
for fluid overload (e.g., those with preexisting congestive heart failure [CHF]) should be instructed
to monitor their weight frequently after the first
dose and report weight gains of 3 to 5 pounds above
baseline to the clinical team.
Based on data from early clinical trials,
administration of very low-dose dexamethasone
(4 mg) prior to carfilzomib in cycles 1 and 2 is
Patient Management
Many of the more frequently reported AEs
such as fatigue, dyspnea, and infections can be
alleviated with proper prophylactic measures,
including hydration, dexamethasone, and antiviral/
antibacterials (Table 3). Fatigue, which is commonly
observed following carfilzomib use, was the most
common treatment-emergent AE observed in the
integrated safety analysis of several phase II clinical
trials (Siegel et al., 2013). Dyspnea has been observed
following carfilzomib treatment, both as part of flulike infusion reactions (observed in early phase I
studies [Alsina et al., 2012]) including fever, rigors,
and chills, and at other times during treatment. Antiviral prophylaxis was used in the clinical trials to prevent viral infections in patients with MM, who typically have myelosuppression that can be attributed
to their disease as well as their course of treatment
(Dimopoulos & Terpos, 2010; Mateos, 2010).
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Table 3. Carfilzomib Administration: Recommended Prophylactic Measures
Prophylaxis
Instruction
Purpose
Hydration
Instruct the patient to drink 8 cups of water per
day during dosing
Prevention of fatigue
Reduction in risk of renal toxicity and tumor
lysis syndrome
Administer 250–500 mL IV normal saline
predose and again postdose as needed
Dexamethasone
Administer 4 mg orally or IV prior to all doses
of carfilzomib during cycle 1 and prior to all
carfilzomib doses during the first cycle of dose
escalation to 27 mg/m2
Prevention/alleviation of flu-like (infusionrelated) symptoms
Antivirals
Administer valacyclovir or acyclovir
Particularly important in patients with a history
of herpesvirus infections
Antibacterials
Administer moxifloxacin, levofloxacin,
cotrimoxazole, or ciprofloxacin
Prevention of infections related to
immunosuppression, especially important for
patients at risk of certain infections, including
urinary tract infections and pneumonia
recommended to decrease the potential occurrence
and severity of flu-like infusion-related symptoms,
including dyspnea. In clinical practice, symptoms
to watch for in the first 24 to 48 hours after each
dose include fever, chills, myalgia, facial swelling or
flushing, vomiting, weakness, shortness of breath,
hypotension, and possible chest tightness (Table 4).
Dexamethasone should be reintroduced if symptoms
develop or reappear in subsequent cycles.
It is important for patients to be educated
about the symptoms to watch out for. Additionally,
caregivers should monitor the patient while he or she
is answering a question to determine if they can speak
without experiencing shortness of breath, which
may occur after dosing. Shortness of breath at rest
should also be closely monitored. The patient should
be instructed to inform their health-care provider
immediately if he or she experiences breathing
difficulties so that any respiratory side effects can be
managed appropriately, which may in turn decrease
the likelihood of dose interruptions.
Antiviral prophylaxis (e.g., valacyclovir,
acyclovir) is recommended for patients who
have a history of herpes zoster infections
(Onyx Pharmaceuticals, 2012). In the clinic,
antiviral prophylaxis is often administered to all
patients, and antibacterial prophylaxis should
be considered for patients at risk of urinary tract
infections, pneumonia, and other infections.
Managing Common Adverse Events
In the four phase II clinical trials that
investigated carfilzomib, hematologic AEs
related to myelosuppression were common but
infrequently dose limiting (Nooka et al., 2012). In
the 526 patients included in the phase II trials,
≥ grade 3 thrombocytopenia and neutropenia
were reported in 23.4% and 10.3% of patients,
respectively. Dosing guidelines recommend
that the carfilzomib dose be withheld for grade
4 thrombocytopenia or ≥ grade 3 neutropenia
(Onyx Pharmaceuticals, 2012).
Due to the nature of MM, thrombocytopenia
is commonly seen in the clinic but is generally
mild; discontinuation of therapy due to
thrombocytopenia is low. Approximately a third
of patients have > 50% plasmacytosis in their bone
marrow at baseline, which leads to a reduction
in patients’ platelet count prior to initiating
carfilzomib. Platelet counts typically decrease
during the dosing cycle and return to baseline prior
to the next cycle. Thrombocytopenia is generally
managed first with dose reduction and then with
platelet transfusions if the platelet count falls
Table 4. Signs and Symptoms of Flu-Like
Infusion-Related Reactions
Symptoms to watch for in the first 24 to 48 hours:
•
•
•
•
•
•
Fever
Chills
Weakness
Syncope
Myalgia, arthralgia
Facial swelling and
flushing
• Vomiting
• Shortness of breath and
chest tightness
• Angina
• Hypotension
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SIDE EFFECT PROFILE OF CARFILZOMIB
below 25,000/μL. The carfilzomib dose should
be held for grade 4 thrombocytopenia until the
platelet count surpasses 25,000/μL. It is helpful
to educate patients on the signs and symptoms
of thrombocytopenia: unexpected bruising,
petechiae, bleeding from the nose or gums, severe
headaches, dizziness, and increased fatigue.
Grade 3 neutropenia is observed and commonly treated with growth factors including filgrastim
(Neupogen), 300 or 480 μg subcutaneously (SC)
for 1 to 3 days followed by a complete blood count
within a week, or pegfilgrastim (Neulasta) 6 mg
SC per cycle. The carfilzomib dose is held for an
absolute neutrophil count < 1000/μL; generally
patients are given growth factors and the carfilzomib dose is delayed for 1 to 2 days.
Anemia is usually grade 1 or 2 and managed
with growth factors such as epoetin alfa
(Procrit) 40,000 units SC weekly for hemoglobin
≤ 10 g/dL or darbepoetin alfa (Aranesp) 300
μg SC every 2 weeks or 500 μg each month for
hemoglobin ≤ 10 mg/dL. Transfusions are rarely
required for asymptomatic grade 1/2 anemia, and
although growth factors can lead to side effects,
the benefits of using them generally outweigh the
risks. Anemia ≥ grade 3 (defined as hemoglobin <
8 g/dL, < 4.9 mmol/L [National Cancer Institute,
2010]) typically necessitates transfusions and
sometimes requires dose interruptions and/or
modifications. Rather than hold treatment because
of anemia, carfilzomib can be administered
followed by transfusion of packed cells as needed
for hemoglobin < 8 mg/dL.
Gastrointestinal AEs including nausea,
diarrhea, vomiting, and constipation were common
in phase II studies; however, they were rarely
dose limiting and rarely resulted in treatment
discontinuation (Onyx Pharmaceuticals, 2012;
Siegel et al., 2013). In clinical practice, these AEs
are less worrisome as their frequency and severity
vary significantly from patient to patient. Nausea
is generally mild in severity and very manageable.
Premedicating with antinausea medication is
suggested including oral ondansetron 8 mg, 30
minutes prior to carfilzomib treatment. The
majority of patients do not typically require
additional nausea medication.
Hypomagnesemia and hypokalemia were
observed in the four phase II studies and were
mainly grades 1 or 2 (Onyx Pharmaceuticals,
2012). In the clinic, electrolyte imbalances
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that may require magnesium and potassium
supplementation occur in some patients during
the first cycle as well as throughout treatment.
The imbalances are generally low grade and easily
managed with oral supplements or increased
dietary intake. There may be an occasional need
for IV replacement with severe depletion. It is
recommended that chemistry panels be checked
at least once per cycle, with increased frequency
in the first two cycles depending on the individual
patient.
Consideration of Potential Adverse Events
It is important to comment on the AEs that
occurred infrequently during the four phase II
clinical trials but can potentially be serious nonetheless. Many of these AEs occur because of
comorbidities that are observed in patients with
MM: cardiac, renal, and hepatic AEs that can be
exacerbated upon treatment.
Cardiac AEs have the potential to be serious;
therefore, it is imperative to identify patients
with confounding cardiac risk factors prior to
initiating carfilzomib treatment. The integrated
safety analysis of the phase II studies, from
which patients with New York Heart Association
Class III-IV heart failure or recent myocardial
infarction/unstable angina were excluded,
showed that > 70% of patients had a medical
history of a cardiac event and 70% had cardiac
risk factors at baseline, including hypertension,
diabetes, hyperlipidemia, coronary artery disease,
and CHF (Lonial et al., 2012). Overall, a dose
reduction due to a cardiac AE was required in 6
patients (1.1%); 23 patients (4.4%) discontinued
treatment due to a cardiac AE, including CHF
(1.7%), arrhythmia (1.1%), and ischemic heart
disease (1.0%; Lonial et al., 2012).
Renal dysfunction is common in patients with
MM, and although a majority of the patients in the
phase II carfilzomib studies had renal dysfunction
at baseline, transient worsening of renal function
was reported in 6% of patients. Nontransient
worsening of renal function was reported in 7%
of patients (Harvey et al., 2012). Serious hepatic
disorders in the phase II trials were rare (Siegel
et al., 2013).
In clinical practice, because of the presence
of cardiac risk factors in many patients with RR
MM prior to initiation of carfilzomib therapy, it is
important to be aware of individual symptoms and
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McBRIDE and SAMUEL
CONCLUDING REMARKS
concomitant medications and to manage them
appropriately. In addition, a patient with cardiac
risk factors should be cleared by a cardiologist
prior to treatment. Medication adjustment may be
required during carfilzomib treatment to manage
blood pressure in hypertensive patients. For patients
with CHF, baseline and repeat echocardiograms
may be necessary, taking note of the ejection fraction
as well as any signs of pulmonary hypertension.
Patients with cardiac risk factors need to be closely
monitored for fluid overload, which is most easily
done by monitoring weight.
While renal impairment is not typically
observed in response to carfilzomib treatment
in clinical practice, it is important to recognize
that small, typically transient increases in serum
creatinine are often observed between the two
consecutive doses. The increases are easily
managed with adequate oral and IV hydration.
Dose reduction is not normally required in
patients with renal dysfunction, including
patients on dialysis. Similar to renal impairment,
hepatic impairment is not a significant issue
in the clinic, although occasional elevations in
transaminases are observed. In the event that
hepatic enzymes are elevated, a review of the
patient’s concomitant medications is suggested.
The carfilzomib dose can be reduced if necessary.
Another AE of importance to patients with
MM is PN, which is related either to the disease
or to treatment and is frequently observed in
patients with RR MM (Mohty et al., 2010).
Peripheral neuropathy was not frequently
reported during the four phase II clinical trials of
carfilzomib even though most patients on study
(71.9%) entered with a baseline of PN grade 1
or 2. Notably, newly developed PN occurred
infrequently, and all reported cases of PN were
generally ≤ grade 2 and rarely resulted in dose
modifications or discontinuations (Martin et al.,
2012). As in the clinical trial data summary, PN
is rarely observed in the clinic.
There are certain considerations that are
important in the management of patients with
MM treated with carfilzomib, and a recommended
checklist to aid in patient care is provided in the
Figure. Knowledge of the possible AEs associated
with carfilzomib and the suggested guidelines for
patient management prior to, during, and after
treatment will help to prevent complications
and ensure that prophylactic measures are
implemented to reduce the frequency and severity
of side effects. It is important to educate the
patient on possible side effects and precautions
and to explain the actions to be taken. Establishing
a baseline profile and monitoring the patient
closely throughout the course of treatment will
help to personalize treatment while minimizing
discomfort and AEs.
Finally, the care team should work together,
sharing patient information and encouraging the
patient to communicate any changes or side effects
they experience. The overall treatment goal should
be to maximize the efficacy of carfilzomib while
minimizing AEs and discomfort in the patient.
Being aware of the clinical practice experience
with carfilzomib presented here should help APs
to attain that goal.
ACKNOWLEDGMENT
The authors would like to thank Melissa Kirk,
PhD (Fishawack Communications), for medical
writing and editorial assistance, which was
supported by Onyx Pharmaceuticals, Inc.
DISCLOSURE
Ms. McBride has received payment as a
member of the Onyx Speakers Bureau and
reimbursement for travel, accommodations,
and meeting expenses from L&M Healthcare
Communications. Ms. Samuel has received an
honorarium as a member of the Carfilzomib
Advisory Board.
References appear on page 30
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SIDE EFFECT PROFILE OF CARFILZOMIB
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Recommended Carfilzomib Care Checklist
Prior to Administration
 Perform a thorough history and physical examination
 Obtain records of past echocardiography or pulmonary function tests
 Obtain current medication list
Query patient or caregiver regarding side effects from previous
treatments
Note which medications were used/helpful
Explain the importance of hydration (8 cups of water/day)
and prophylactic dexamethasone as well as any antivirals/
antibiotics necessary
Explain flu-like infusion-related reaction symptoms and timing
Explain precautions to females of childbearing age
Explain patient responsibilities, including:
 Report early signs of shortness of breath
 Stay well hydrated to avoid dehydration
 Inform the doctor before starting new medications
 Monitor weight
 Give IV hydration for the first cycle and make sure the patient is well
hydrated for all cycles
 Administer dexamethasone premedication for the first cycle and as
needed for later cycles
 Check weight prior to treatment
During Administration
 Monitor for fluid overload
Post Administration
 Monitor for infusion-related reactions (e.g., flu-like symptoms)
 Monitor for injection site-related reactions (e.g., phlebitis)
 Monitor for fluid overload
 Monitor vital signs for 30 minutes after infusion for changes in blood
pressure, temperature, and pulse
Figure. Recommended carfilzomib patient care checklist.
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