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Carboplatin Dosing - Adult - Inpatient/Ambulatory

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Carboplatin Dosing – Adult – Inpatient/Ambulatory- Clinical Practice Guideline
Target Population: Adult inpatients requiring carboplatin within inpatient and ambulatory setting
Guideline Contact for Content Questions
Name: Philip Trapskin, PharmD, BCPS
Phone Number: 265-0341
Email Address: ptrapskin@uwhealth.org
Coordinating Team Members:
Jason Bergsbaken, PharmD
Mary Mably, RPh, BCOP
Hayley Lincoln, DPH-4
Jessica Wirkus, MS-WHNP, BC, APNP
Lisa Barroilhet, MD
Committee Approvals/Dates:
Pharmacy Oncology Service Line/February 2014
Chemotherapy Review Council/May 2014
Pharmacy & Therapeutics Committee/June 2014
Copyright © 2014 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 06/2014CCKM@uwhealth.org

2
Table of Contents
EXECUTIVE SUMMARY……………………………………………………………………………………………………………………… 3
SCOPE……………………………………………………………………………………………………………………………………………… 6
METHODOLOGY……….……………………………………………………………………………………………………………………… 6
DEFINITIONS….……………………………………………………………………………………………………………………………….. 7
INTRODUCTION……….……………………………………………………………………………………………….……………………… 7
RECOMMENDATIONS….……………………………………………………………………………………………….………….…….… 8
IMPLEMENTATION PLAN….………………………………………………………………………………………….………….…….… 12
DISCLAIMER..….……………………………………………………………………………………………….………….…….…………. 12
REFERENCES FOR SUPPORTING EVIDENCE.…………………………………………………………………….………………… 13
Copyright © 2014 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 06/2014CCKM@uwhealth.org

3
Clinical Practice Guideline Executive Summary
Guideline Title
Carboplatin Dosing – Adults – Inpatient/Ambulatory – Clinical Practice Guideline
Guideline Overview
This guideline is intended to guide clinicians on carboplatin dosing within inpatient and
ambulatory settings for adult patients
Key Practice Recommendations
1. Carboplatin Dose Calculations
1.1. Dosing of carboplatin should be calculated using the Calvert equation (excluding research
protocol driven dosing using body surface area or weight-based dosing):
Total Dose (mg)= target AUC* (GFR+25), GFR may be substituted by CrCL7,8,9 (Class I,
Level of Evidence A)
1.2. Dosing of carboplatin is typically directed at a specific AUC target, allowing oncologists to
target a patient or protocol specific carboplatin therapeutic index for each treatment. The
AUC goal may range from two to six and is dependent on diagnostic and patient-specific
factors.10
1.3. The creatinine clearance (CrCl) should be calculated by the Cockcroft-Gault equation:
7,8,9
(Class IIa, Level of Evidence A)
1.3.1. Use of actual body weight, regardless of a high body mass index (BMI), when selecting
the dose of cytotoxic chemotherapy agents is reasonable7 (Class IIa, Level of Evidence A)
1.3.1.1. Optimal dosing of carboplatin in the morbidly obese is still somewhat unclear. It
may be reasonable to use actual body weight dosing, with consideration of the
patient’s other comorbidities7 (Class IIb, Level of Evidence C)
1.3.1.2. It is reasonable to set a minimum serum creatinine value of 0.7 mg/dL and a
CrCl cap of 125 mL/min5,7,11 (Class IIa, Level of Evidence A)
1.3.1.3. If concern for over or under dosing in patients, an actual creatinine clearance
through a 24 hour urine collection is indicated9 (Class I, Level of Evidence A)
2. Carboplatin Monitoring
2.1. Complete blood count with differential and platelets: Monitor absolute neutrophil count and
platelets9 (Class I, Level of Evidence B)
2.2. Electrolytes: Monitor sodium, potassium, magnesium and calcium levels while a patient is
receiving carboplatin, as it can lead to electrolyte wasting9 (Class I, Level of Evidence C)
2.2.1. May consider replacing electrolytes, if levels are below normal range9 (Class IIa, Level of
Evidence C)
2.3. Kidney function tests: Carboplatin can potentiate the nephrotoxic effects of other compounds,
despite limited nephrotoxic potential as a single-agent; it is beneficial to monitor the blood
urea nitrogen, serum creatinine, and creatinine clearance9 (Class IIa, Level of Evidence A)
2.4. Liver function tests: May consider monitoring the total bilirubin, aminotransferase, and
alkaline phosphatase9 (Class IIa, Level of Evidence C)
2.5. Audiology tests: May consider having the patient undergo a baseline audiogram with
subsequent checks to assess for hearing loss9,13 (Class IIa, Level of Evidence B)
Copyright © 2014 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 06/2014CCKM@uwhealth.org

4
3. Carboplatin Dose Adjustments
3.1. Impaired Kidney Function
3.1.1. Patients with creatinine clearance less than 60 mL/min are at increased risk for severe
bone marrow suppression; recommend to monitor for toxicities and adjust the dose of
carboplatin if grade 3 or 4 toxicities arise9,13 (Class I, Level of Evidence C)
3.2. Toxicities
3.2.1. Myelosuppression
3.2.1.1. Consider adjusting carboplatin dose based upon the patient’s neutrophil and/or
platelet count12 (Class IIa, Level of Evidence B)
3.2.1.2. If at the carboplatin nadir:
3.2.1.2.1. It is reasonable for no adjustment if platelet count 50,000 to 100,000/ mm3
and/or neutrophil count 500 to 2,000/mm3 9 (Class IIa, Level of Evidence B)
3.2.1.2.2. Consider decreasing carboplatin dose by 25% if platelet count less than
50,000/ mm3 and/or neutrophil count less than 500/mm3 9 (Class IIa, Level
of Evidence B)
3.2.2. Nephrotoxicity
3.2.2.1. Recommend to adjust carboplatin dose based upon the patient’s creatinine
clearance (see 1.1-1.3, 3.1 for further guidance)9,12 (Class I, Level of Evidence A)
3.2.3. Ototoxicity
3.2.3.1. May consider an audiogram prior to therapy (baseline) and subsequent checks
throughout therapy to assess for hearing loss13 (Class IIa, Level of Evidence B)
3.2.3.2. A dose adjustment or therapy discontinuation may be considered for clinically
significant hearing changes (grade 3 or 4 toxicity)13,14 (Class IIa, Level of Evidence
C)
3.2.4. Gastrointestinal
3.2.4.1. Carboplatin is a chemotherapeutic agent of moderate emetogenicity (30-90%
experience nausea and vomiting)10; both nausea and vomiting due to
carboplatin administration appear to be responsive to antiemetic therapies9
3.2.4.1.1. Recommend moderate antiemetic therapy to prevent nausea and
vomiting (refer to UW Health Guidelines for the Prevention and
Treatment of Chemotherapy-Induced Nausea and Vomiting in Adults)10
(Class I, Level of Evidence A)
3.2.4.1.2. If a patient is still experiencing nausea and vomiting while on the
moderate antiemetic therapy, may consider increasing to the high
antiemetic therapy10 (Class IIa, Level of Evidence C)
3.2.4.2. Carboplatin may cause delayed emesis (emesis that occurs greater than 24
hours after chemotherapy) in patients10
3.2.4.2.1. For patients experiencing delayed emesis, addition of a NK1 antagonist,
such as aprepitant or fosaprepitant, to the patient’s antiemetic therapy
may be considered (Class IIa, Level of Evidence A)10
3.2.5. Neurotoxicity
3.2.5.1. Consider performing routine neurologic exams 14 (Class IIa, Level of Evidence C)
3.2.5.1.1. May be reasonable to use gabapentin, pregabalin, glutathione, vitamin
E, or calcium/magnesium infusion therapy; have shown some efficacy
with conflicting evidence12,15 (Class IIb, Level of Evidence B)
3.2.5.1.2. Dose adjustment or therapy discontinuation is recommended in
patients experiencing clinically significant toxicity (grade 3 or 4)13,14
(Class I, Level of Evidence C)
Copyright © 2014 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 06/2014CCKM@uwhealth.org

5
4. Carboplatin Hypersensitivity and Desensitization
4.1. Hypersensitivity
4.1.1. Patients undergoing carboplatin therapy may experience a hypersensitivity reaction
4.1.2. Symptoms of hypersensitivity reactions can manifest in many forms including mild rash,
urticaria, temporary flushing, fever, dyspnea, bronchospasm, throat/chest tightness,
tachycardia and hypotension/hypertension13,16,17,18,19
4.1.3. Skin testing for hypersensitivity
4.1.3.1. If a patient has experienced hypersensitivity symptoms while receiving
carboplatin previously, it may be considered to have the patient undergo the
following skin test prior to their next infusion20 (Class IIa, Level of Evidence B):
4.1.3.1.1. Inject 0.02 mL of undiluted carboplatin by intradermal injection to the
patient’s inner forearm
4.1.3.1.2. Examine site at five, fifteen, and thirty minutes post-administration for
signs of hypersensitivity reaction; specifically, erythema and localized
raised skin at the site of the injection (a wheal)
4.1.3.2. Skin test results:
4.1.3.2.1. Positive test
4.1.3.2.1.1. Wheal is equal to or greater than 5 mm in diameter surrounded by
erythema (wheal-and-flare reaction); if the wheal is greater than or
equal to 1 cm in diameter, it is considered a strongly positive test
4.1.3.2.2. Borderline positive test
4.1.3.2.2.1. If the wheal is just less than 5 mm in diameter or had an indefinite
wheal and only slight erythema
4.1.3.3. If the patient has a positive or borderline positive skin test, a desensitization
therapy, as seen below, may be considered (Class IIa, Level of Evidence B)
4.1.3.4. If a patient who had a negative skin test develops a hypersensitivity reaction
during a carboplatin administration, the desensitization therapy may also be
considered as false negative skin tests may occur (Class IIa, Level of Evidence C)
4.2. Desensitization
4.2.1. If a patient has experienced a reaction or hypersensitivity to carboplatin previously, a
desensitization protocol may be considered16 (Class IIa, Level of Evidence B)
4.2.2. The following is a suggested 6 hour, 12 step desensitization therapy for patients with a
hypersensitivity to carboplatin and is approved for use at UW Health16:
4.2.2.1. This protocol should be undergone with each subsequent carboplatin
administration the patient receives16 (Class I, Level of Evidence B)
4.2.2.2. Desensitization premedication:16
- Dexamethasone 12mg by mouth every six hours for a total of four doses
prior to treatment (starting 24 hours prior to carboplatin infusion)
- Diphenhydramine 50mg by mouth 30 minutes prior to carboplatin infusion
- Ranitidine 50 mg (or another H2 antagonist) intravenously for one dose 30
minutes prior to carboplatin infusion
- Lorazepam 0.5mg to 1mg PO every 6 hours as needed for anxiety
4.2.3. Three different infusion concentration solutions of carboplatin should be created, and
will be referred to as Solution A, B, and C (Class IIa, Level of Evidence B) 16:
***The tubing attached to each bag containing different solutions should be primed
with carboplatin in the line
4.2.3.1. Solution A is 1/100th of the total dose diluted in 250 mL of dextrose 5% water
Copyright © 2014 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 06/2014CCKM@uwhealth.org

6
4.2.3.2. Solution B is 1/10th of the total dose diluted in 250 mL of dextrose 5% water
4.2.3.3. Solution C is calculated to be the remainder of the total dose that has not yet
been added to Solution A or B diluted in 250mL of dextrose 5% water
4.2.3.3.1. Begin infusing Solution A at 2 mL/hr for a total of 15 minutes, then
increase to 5 mL/hr for 15 minutes, then 10 mL/hr for 15 minutes, and
then 20 mL/hr for 15 minutes
4.2.3.3.2. Stop Solution A, discard, and begin infusing Solution B
4.2.3.3.3. Begin infusing Solution B at 5 mL/hr for a total of 15 minutes, then
increase to 10 mL/hr for 15 minutes, then 20 mL/hr for 15 minutes, then
40 mL/hr for 15 minutes
4.2.3.3.4. Stop Solution B, discard, and begin infusing Solution C
4.2.3.3.5. Begin infusing Solution C at 10 mL/hr for 15 minutes, then 20 mL/hr for
15 minutes, then 40 mL/hr for 15 minutes, and then infuse the
remainder at 75 mL/hr
4.2.4. If further hypersensitivity reactions occur during the carboplatin desensitization16:
4.2.4.1. Stop the infusion and, depending on the severity, may treat with
diphenhydramine 25-50 mg IV as needed, dexamethasone 4-10 mg IV as needed
and/or albuterol 2.5 mg by nebulizer as needed
4.2.4.2. Following the resolution of reaction, may consider restarting the infusion at the
same rate infusing when the desensitization therapy was discontinued while
continuing to monitor the patient16
4.2.4.3. Intermediate rate increases may be deemed appropriate after a hypersensitivity
reaction, but total carboplatin dose received must remain equivalent16
Scope
1. Disease/Condition(s): Adult patients requiring carboplatin dosing
2. Clinical Specialty: Hematology, Oncology
3. Intended Users: Physicians, Physician Assistants, Advanced Practice Nurses, Pharmacists,
Nurses
4. CPG objective(s): To provide recommendations for the dosing, administration and monitoring
of carboplatin
5. Target Population: Inpatient or ambulatory adult patients requiring carboplatin
Methodology
1. Methods Used to Collect/Select the Evidence
1.1. Searches of electronic databases (e.g., national and international guidelines for
carboplatin dosing and/or treatment)
2. Methods Used to Assess the Quality and Strength of the Evidence: Weighing according to rating
scheme (scheme given below).
3. A modified Grading of Recommendations Assessment, Development and Evaluation (GRADE)
developed by the American Heart Association and American College of Cardiology (Figure 1)
have been used to assess the Quality and Strength of the Evidence in this Clinical Practice
Guideline1
Figure 1: Quality of Evidence and Strength of Recommendation Grading Matrix
Copyright © 2014 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 06/2014CCKM@uwhealth.org

7
Definitions
1. Creatinine Clearance (CrCl): measure of the rate in which creatinine, a byproduct of protein
metabolism, is cleared from the blood by the kidneys2
2. Glomerular Filtration Rate (GFR): quantity of glomerular filtrate formed each minute in the
nephrons located in the kidneys3
3. Area under the curve (AUC): measurement of the bioavailability of a drug based upon the blood
concentrations in the body at certain intervals of time after administration3
4. Calvert formula: calculation of the carboplatin dose derived from the GFR and targeted AUC3:
Introduction
Carboplatin is a platinum-based antineoplastic agent that is used in many different chemotherapy
regimens for multiple cancer disease states, including, but not limited to, gynecologic, lung and
breast malignancies.4 Dosing for carboplatin is based upon body surface area or, more commonly,
the Calvert formula which accounts for target drug exposure and changes in kidney function:
The glomerular filtration rate (GFR) in this equation was
originally calculated through the clearance of a radioactive compound chromium 51-
ethylenediaminetetraacetic acid; however, it is not always available or practical for use. Thus, the
GFR is substituted by a creatinine clearance (CrCl) estimate through the Cockcroft-Gault equation:
*Modified Grading of Recommendations Assessment, Development and Evaluation (GRADE)
developed by the American Heart Association and American College of Cardiology
Copyright © 2014 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 06/2014CCKM@uwhealth.org

8
Controversy exists in carboplatin dosing strategies as some oncologists and research groups (such as
the Gynecologic Oncology Group (GOG)) recommend carboplatin dosing based on ideal or adjusted
body weight to reduce potential toxicities. Historically, some providers have set a minimum serum
creatinine of 0.7 mg/dL, capped maximum creatinine clearances (CrCl of 125 mL/min), and/or
specified a maximum carboplatin dose per the recommendation of the Food and Drug
Administration (FDA) and other bodies.5 These differences in dosing strategy may potentially impact
recurrence rates, as well as, morbidity and mortality.6,7 Thus, this guideline was established on
evidence-based literature to encourage consistency in carboplatin dosing strategies at UW Health.
Recommendations
5. Carboplatin Dose Calculations
5.1. Dosing of carboplatin should be calculated using the Calvert equation (excluding research
protocol driven dosing using body surface area or weight-based dosing):
Total Dose (mg)= target AUC* (GFR+25), GFR may be substituted by CrCL7,8,9 (Class I,
Level of Evidence A)
5.2. Dosing of carboplatin is typically directed at a specific AUC target, allowing oncologists to target
a patient or protocol specific carboplatin therapeutic index for each treatment. The AUC goal
may range from two to six and is dependent on diagnostic and patient-specific factors.10
5.3. The CrCl should be calculated by the Cockcroft-Gault equation:
7,8,9
(Class I, Level of Evidence A)
5.3.1. Use of actual body weight, regardless of a high body mass index (BMI), when selecting
the dose of cytotoxic chemotherapy agents is reasonable7 (Class IIa, Level of Evidence A)
5.3.1.1. Optimal dosing of carboplatin in the morbidly obese is still somewhat unclear. It
may be reasonable to use actual body weight dosing, with consideration of the
patient’s other comorbidities7 (Class IIb, Level of Evidence C)
5.3.1.2. It is reasonable to set a minimum serum creatinine value of 0.7 mg/dL and a
CrCl cap of 125 mL/min5,7,11 (Class IIa, Level of Evidence A)
5.3.1.3. If concern for over or under dosing in patients, an actual creatinine clearance
through a 24 hour urine collection is indicated9 (Class I, Level of Evidence A)
6. Carboplatin Monitoring
6.1. Complete blood count with differential and platelets: Monitor absolute neutrophil count and
platelets9 (Class I, Level of Evidence B)
6.2. Electrolytes: Monitor sodium, potassium, magnesium and calcium levels while a patient is
receiving carboplatin, as it can lead to electrolyte wasting9 (Class I, Level of Evidence C)
6.2.1. May consider replacing electrolytes, if levels are below normal range9 (Class IIa, Level of
Evidence C)
6.3. Kidney function tests: Carboplatin can potentiate the nephrotoxic effects of other compounds,
despite limited nephrotoxic potential as a single-agent; it is beneficial to monitor the blood
urea nitrogen, serum creatinine, and creatinine clearance9 (Class IIa, Level of Evidence A)
6.4. Liver function tests: May consider monitoring the total bilirubin, aminotransferase, and alkaline
phosphatase9 (Class IIa, Level of Evidence C)
6.5. Audiology tests: May consider having the patient undergo a baseline audiogram with
subsequent checks to assess for hearing loss9,13 (Class IIa, Level of Evidence B)
Copyright © 2014 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 06/2014CCKM@uwhealth.org

9
7. Carboplatin Dose Adjustments
7.1. Impaired Kidney Function
7.1.1. Patients with creatinine clearance less than 60 mL/min are at increased risk for severe
bone marrow suppression due to decreased clearance of carboplatin; recommend to
monitor for toxicities and adjust the dose of carboplatin if grade 3 or 4 toxicities arise9,13
(Class I, Level of Evidence C)
7.2. Toxicities
7.2.1. Myelosuppression
7.2.1.1. Bone marrow suppression, specifically neutropenia and thrombocytopenia, is a
dose limiting toxicity with carboplatin-induced thrombocytopenia occurring in
20-40% of patients and severe neutropenia arising in less than 20%12
7.2.1.2. Myelosuppression is typically more severe in patients with impaired renal
function and/or when carboplatin is combined with other bone marrow
suppressing agents/radiotherapy9
7.2.1.3. Consider adjusting carboplatin dose based upon the patient’s neutrophil and/or
platelet count12 (Class IIa, Level of Evidence B)
7.2.1.4. If at the carboplatin nadir:
7.2.1.4.1. It is reasonable for no adjustment if platelet count 50,000 to 100,000/ mm3
and/or neutrophil count 500 to 2,000/mm3 9 (Class IIa, Level of Evidence B)
7.2.1.4.2. Consider decreasing carboplatin dose by 25% if platelet count less than
50,000/ mm3 and/or neutrophil count less than 500/mm3 9 (Class IIa, Level
of Evidence B)
Nadir post carboplatin administration9 (Class IIa, Level of Evidence B):
Platelets: Neutrophils:
50,000-100,000/ mm3 500-2,000/ mm3 No adjustment in dose
<50,000/ mm3 <500/ mm3 Consider decreasing next dose by 25%
7.2.2. Nephrotoxicity
7.2.2.1. Carboplatin-linked renal impairment is a rare occurrence; however, carboplatin
may potentiate renal impairment with preexisting irregular kidney function12
7.2.2.2. Recommend to adjust carboplatin dose based upon the patient’s creatinine
clearance (see 1.1-1.3, 3.1 for further guidance)9,12 (Class I, Level of Evidence A)
7.2.3. Ototoxicity
7.2.3.1. When the serum concentration of carboplatin is high, ototoxicity has the
potential to occur, with an incidence of about 1%12
7.2.3.2. May consider an audiogram prior to therapy (baseline) and subsequent checks
throughout therapy to assess for hearing loss13 (Class IIa, Level of Evidence B)
7.2.3.3. A dose adjustment or therapy discontinuation may be considered for clinically
significant hearing changes (grade 3 or 4 toxicity)13,14 (Class IIa, Level of Evidence
C)
7.2.4. Gastrointestinal
7.2.4.1. Carboplatin is a chemotherapeutic agent of moderate emetogenicity (30-90%
experience nausea and vomiting)10; both nausea and vomiting due to
carboplatin administration appear to be responsive to antiemetic therapies9
7.2.4.1.1. Recommend moderate antiemetic therapy to prevent nausea and
vomiting (refer to UW Health Guidelines for the Prevention and
Copyright © 2014 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 06/2014CCKM@uwhealth.org

10
Treatment of Chemotherapy-Induced Nausea and Vomiting in Adults)10
(Class I, Level of Evidence A)
7.2.4.1.2. If a patient is still experiencing nausea and vomiting while on the
moderate antiemetic therapy, may consider increasing to the high
antiemetic therapy10 (Class IIa, Level of Evidence C)
7.2.4.2. Carboplatin may cause delayed emesis (emesis that occurs greater than 24
hours after chemotherapy) in patients10
7.2.4.2.1. For patients experiencing delayed emesis, addition of a NK1 antagonist,
such as aprepitant or fosaprepitant, to the patient’s antiemetic therapy
may be considered (Class IIa, Level of Evidence A)10
7.2.5. Neurotoxicity
7.2.5.1. Consider performing routine neurologic exams 14 (Class IIa, Level of Evidence C)
7.2.5.1.1. Carboplatin has a low frequency of neurotoxicity (6% incidence)12
7.2.5.1.2. May be reasonable to use gabapentin, pregabalin, glutathione, vitamin
E, or calcium/magnesium infusion therapy; have shown some efficacy
with conflicting evidence12,15 (Class IIb, Level of Evidence B)
7.2.5.1.3. Dose adjustment or therapy discontinuation is recommended in
patients experiencing clinically significant toxicity (grade 3 or 4)13,14
(Class I, Level of Evidence C)
8. Carboplatin Hypersensitivity and Desensitization
8.1. Hypersensitivity
8.1.1. Patients undergoing carboplatin therapy may experience a hypersensitivity reaction
8.1.1.1. Reaction does not typically occur with the first exposure to carboplatin
8.1.1.2. Incidence of hypersensitivity reactions increases to 27% after 7 cycles of
therapy16,17
8.1.2. Symptoms of hypersensitivity reactions can manifest in many forms including mild rash,
urticaria, temporary flushing, fever, dyspnea, bronchospasm, throat/chest tightness,
tachycardia and hypotension/hypertension13,16,17,18,19
8.1.3. Skin testing for hypersensitivity
8.1.3.1. If a patient has experienced hypersensitivity symptoms while receiving
carboplatin previously, it may be considered to have the patient undergo the
following skin test prior to their next infusion20 (Class IIa, Level of Evidence B):
8.1.3.1.1. Inject 0.02 mL of undiluted carboplatin by intradermal injection to the
patient’s inner forearm
8.1.3.1.2. Examine site at five, fifteen, and thirty minutes post-administration for
signs of hypersensitivity reaction; specifically, erythema and localized
raised skin at the site of the injection (a wheal)
8.1.3.2. Skin test results:
8.1.3.2.1. Positive test
8.1.3.2.1.1. Wheal is equal to or greater than 5 mm in diameter surrounded by
erythema (wheal-and-flare reaction); if the wheal is greater than or
equal to 1 cm in diameter, it is considered a strongly positive test
8.1.3.2.2. Borderline positive test
8.1.3.2.2.1. If the wheal is just less than 5 mm in diameter or had an indefinite
wheal and only slight erythema
8.1.3.3. If the patient has a positive or borderline positive skin test, a desensitization
therapy, as seen below, may be considered (Class IIa, Level of Evidence B)
Copyright © 2014 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 06/2014CCKM@uwhealth.org

11
8.1.3.4. If a patient who had a negative skin test develops a hypersensitivity reaction
during a carboplatin administration, the desensitization therapy may also be
considered as false negative skin tests may occur (Class IIa, Level of Evidence C)
8.2. Desensitization
8.2.1. If a patient has experienced a reaction or hypersensitivity to carboplatin previously, a
desensitization protocol may be considered16 (Class IIa, Level of Evidence B)
8.2.2. The following is a suggested 6 hour, 12 step desensitization therapy for patients with a
hypersensitivity to carboplatin and is approved for use at UW Health16:
8.2.2.1. This protocol should be undergone with each subsequent carboplatin
administration the patient receives16 (Class I, Level of Evidence B)
8.2.2.2. Desensitization premedication:16
- Dexamethasone 12mg by mouth every six hours for a total of four doses
prior to treatment (starting 24 hours prior to carboplatin infusion)
- Diphenhydramine 50mg by mouth 30 minutes prior to carboplatin infusion
- Ranitidine 50 mg (or another H2 antagonist) intravenously for one dose 30
minutes prior to carboplatin infusion
- Lorazepam 0.5mg to 1mg PO every 6 hours as needed for anxiety
8.2.3. Three different infusion concentration solutions of carboplatin should be created, and
will be referred to as Solution A, B, and C (Class IIa, Level of Evidence B) 16:
***The tubing attached to each bag containing different solutions should be primed
with carboplatin in the line
8.2.3.1. Solution A is 1/100th of the total dose diluted in 250 mL of dextrose 5% water
8.2.3.2. Solution B is 1/10th of the total dose diluted in 250 mL of dextrose 5% water
8.2.3.3. Solution C is calculated to be the remainder of the total dose that has not yet
been added to Solution A or B diluted in 250mL of dextrose 5% water
8.2.3.3.1. Begin infusing Solution A at 2 mL/hr for a total of 15 minutes, then
increase to 5 mL/hr for 15 minutes, then 10 mL/hr for 15 minutes, and
then 20 mL/hr for 15 minutes
8.2.3.3.2. Stop Solution A, discard, and begin infusing Solution B
8.2.3.3.3. Begin infusing Solution B at 5 mL/hr for a total of 15 minutes, then
increase to 10 mL/hr for 15 minutes, then 20 mL/hr for 15 minutes, then
40 mL/hr for 15 minutes
8.2.3.3.4. Stop Solution B, discard, and begin infusing Solution C
8.2.3.3.5. Begin infusing Solution C at 10 mL/hr for 15 minutes, then 20 mL/hr for
15 minutes, then 40 mL/hr for 15 minutes, and then infuse the
remainder at 75 mL/hr
8.2.4. If further hypersensitivity reactions occur during the carboplatin desensitization16:
8.2.4.1. Stop the infusion and, depending on the severity, may treat with
diphenhydramine 25-50 mg IV as needed, dexamethasone 4-10 mg IV as needed
and/or albuterol 2.5 mg by nebulizer as needed
8.2.4.2. Following the resolution of reaction, may consider restarting the infusion at the
same rate infusing when the desensitization therapy was discontinued while
continuing to monitor the patient16
8.2.4.3. Intermediate rate increases may be deemed appropriate after a hypersensitivity
reaction, but total carboplatin dose received must remain equivalent16
Copyright © 2014 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 06/2014CCKM@uwhealth.org

12
UW Health Implementation
Implementation Plan/Tools
The guideline will be available on UConnect and cross referenced in guidelines and protocols.
Information regarding availability of this new guideline will be disseminated to pertinent Disease
Related Working Groups (DOWGs).
Disclaimer
This Clinical Practice Guideline provides an evidence-based approach for use of carboplatin. It is
understood that occasionally patients will not match the conditions considered in the guideline.
Copyright © 2014 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 06/2014CCKM@uwhealth.org

13
References
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with normal renal function, does weight matter? Cancer Chemother Pharmacol. 2009;64(1):115-
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5. Carboplatin Dose Calculation Instructions. Gynecology Oncology Group web site.
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patients with cancer: American Society of Clinical Oncology clinical practice guideline. Alexandria
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8. Hall RG 2nd, Jean GW, Sigler M, et al. Dosing considerations for obese patients receiving cancer
chemotherapeutic agents. Ann Pharmacother. 2013;47(12):1666-1674.
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11. Food and Drug Administration Website.
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228974.htm. Updated October 8, 2010. Accessed February 6, 2014.
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Published August 9, 2006. Accessed November 15, 2013.
14. Medsafe. Carboplatin Injection.
http://www.medsafe.govt.nz/profs/Datasheet/c/Carboplatininj.pdf. Updated October 27, 2010.
Accessed February 6, 2014.
15. Amptoulach S, Tsavaris N. Neurotoxicity caused by the treatment with platinum
analogues. Chemother Res Pract. 2011;2011:843019.
16. Lee CW, Matulonis UA, Castells MC. Carboplatin hypersensitivity: a 6-h 12-step protocol
effective in 35 desensitizations in patients with gynecological malignancies and mast cell/IgE-
mediated reactions. Gynecol Oncol. 2004;95(2):370-376.
17. Lee CW, Matulonis UA, Castells MC. Rapid inpatient/outpatient desensitization for
chemotherapy hypersensitivity: standard protocol effective in 57 patients for 255
courses. Gynecol Oncol. 2005;99(2):393-399.
18. Polyzos A, Tsavaris N, Kosmas C, et al. Hypersensitivity reactions to carboplatin administration
are common but not always severe: a 10-year experience. Oncology. 2001;61(2):129-133.
19. Markman M, Kennedy A, Webster K, et al. Clinical features of hypersensitivity reactions to
carboplatin. J Clin Oncol. 1999;17(4):1141.
Copyright © 2014 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 06/2014CCKM@uwhealth.org

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20. Markman M, Zanotti K, Peterson G, et al. Expanded experience with an intradermal skin test to
predict for the presence or absence of carboplatin hypersensitivity. J Clin Oncol.
2003;21(24):4611-464.
Copyright © 2014 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 06/2014CCKM@uwhealth.org