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CABAPRED

Cancer Type: Genitourinary, Prostate  Intent: Palliative
Regimen Category: Evidence-Informed
Funding:
New Drug Funding Program
    Cabazitaxel - Metastatic Castrate-Resistant Prostate Cancer
ODB - General Benefit
    prednisone
A - Regimen Name

CABAPRED Regimen
Cabazitaxel-Prednisone


Disease Site
Genitourinary - Prostate

Intent
Palliative

Regimen Category
Evidence-Informed :

Regimen is considered appropriate as part of the standard care of patients; meaningfully improves outcomes (survival, quality of life), tolerability or costs compared to alternatives (recommended by the Disease Site Team and national consensus body e.g. pan-Canadian Oncology Drug Review, pCODR).  Recommendation is based on an appropriately conducted phase III clinical trial relevant to the Canadian context OR (where phase III trials are not feasible) an appropriately sized phase II trial. Regimens where one or more drugs are not approved by Health Canada for any indication will be identified under Rationale and Use.


Rationale and Uses

Treatment of patients with metastatic castration resistant (hormone refractory) prostate cancer (mCRPC), who have progressed on or within 12 months of completing docetaxel-containing therapy. Not funded for first-line treatment of mCRPC, combination treatment with abiraterone or enzalutamide, or in patients who have failed abiraterone or enzalutamide for mCRPC in the post-docetaxel setting.


Supplementary Public Funding

cabazitaxel
New Drug Funding Program (Cabazitaxel - Metastatic Castrate-Resistant Prostate Cancer) (NDFP Website )

prednisone
ODB - General Benefit (prednisone) (ODB Formulary )

 
B - Drug Regimen

cabazitaxel

*

20 to 25 mg /m² IV Day 1
prednisone
10 mg PO Daily

Patients who are receiving a GnRH agonist should continue to receive the GnRH agonist during cabazitaxel treatment.

* cabazitaxel 25 mg/m2 may be used in select patients at the physician’s discretion.

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C - Cycle Frequency

REPEAT EVERY 21 DAYS

Continue until disease progression or unacceptable toxicity

(de Bono et al. limited duration to 10 cycles because of the risk of cardiotoxicity in the mitoxantrone arm)

 
D - Premedication and Supportive Measures

Antiemetic Regimen:

Low

Other Supportive Care:

Also refer to CCO Antiemetic Recommendations.

 
  • Hemoglobin and hematocrit should be checked prior to treatment.

  • The product monograph recommends that primary G-CSF prophylaxis be considered in patients at higher risk of complications from prolonged neutropenia (e.g. age > 65 years, poor performance or nutritional status, previous occurrence of febrile neutropenia, extensive prior radiation ports, or other serious comorbidities).

  • Also refer to CCO GCSF recommendations.

 

Pre-medications (prophylaxis for infusion reaction):

At least 30 minutes prior to each administration of cabazitaxel:

  • A corticosteroid IV/PO (e.g. Dexamethasone 8 mg)

  • An H1-receptor antagonist IV/PO (e.g. Diphenhydramine 25 mg)

  • An H2- receptor antagonist IV/PO (e.g. Ranitidine 50 mg)

 

 
E - Dose Modifications

Doses should be modified according to the protocol by which the patient is being treated. The following recommendations have been adapted from clinical trials or product monographs and could be considered.

Dosage with toxicity

 

  Dose (mg/m2) Dose (mg/m2)
Starting dose 25 20
First reduction 20 15
Second reduction 15 Discontinue
 
 
 

Adverse reactions / Counts
(x 109/L)

Action

Dose for Next Cycle*

Neutrophils < 1.5;
platelets < 100

Hold until ANC >1.5 and platelets ≥ 100

No change

Neutropenia grade ≥3 for ≥ 7 days (despite supportive care)

Hold until ANC >1.5 and platelets ≥ 100, then

↓ 1 dose level

Febrile neutropenia or thrombocytopenic bleeding

Hold until ANC >1.5 and platelets ≥ 100, then

↓ 1 dose level

Diarrhea grade 2 persisting despite adequate supportive care

Hold until recovery to grade ≤1

↓ 1 dose level

Diarrhea or other organ/ non- hematologic toxicity grade 3

Hold until recovery to ≤ grade 2

↓ 1 dose level

Grade 3 peripheral neuropathy

Hold until recovery to ≤ grade 2

↓ 1 dose level

Grade 3 GI perforation/hemorrhage

Hold
or
Discontinue

↓ 1 dose level
or
Not applicable

Grade 4 organ, other non-hematologic toxicity

Discontinue

Not applicable

≥ grade 3 renal failure

Discontinue

Not applicable

New or worsening respiratory symptoms Hold and investigate Discontinue if confirmed pneumonitis/ILD or ARDS
Signs & symptoms suggesting cystitis Hold and investigate Consider discontinuing if confirmed cystitis

*Do not retreat until neutrophils > 1.5 x 109/L, platelets ≥ 100 x 109/L and other toxicity ≤ grade 2 (grade 1 for persistent diarrhea)

**Discontinue if toxicity continues at reduced dose

 

Management of Infusion Reactions

Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.

 

Grade Management Re-Challenge
1 or 2
  • Stop or slow the infusion rate.
  • Manage the symptoms.

Restart:

  • After symptom resolution, restart with pre-medications ± reduced infusion rate.
  • Consider re-challenge with pre-medications and at a reduced infusion rate.
  • After 2 subsequent IRs, replace with a different taxane. Give intensified pre-medications and reduce the infusion rate.
  • May consider adding oral montelukast ± oral acetylsalicylic acid.
3 or 4
  • Stop treatment
  • Aggressively manage symptoms.
  • Re-challenge is discouraged, especially if vital symptoms have been affected.
  • Consider desensitization if therapy is necessary.
  • There is insufficient evidence to recommend substitution with another taxane at re-challenge
  • High cross-reactivity rates have been reported.

 



Hepatic Impairment

Formal studies have not been conducted in patients with severe hepatic impairment.

Total Bilirubin

 

AST/ALT

Dose (mg/m2)

< ULN

and

<1.5 x ULN

No change

>1 to ≤ 1.5 x ULN

or

>1.5 x ULN

20 (monitor carefully)

>1.5 to ≤ 3 x ULN

and

any

15 (unknown efficacy; monitor carefully)

>3 x ULN

and

any

Do not treat


Renal Impairment

No dosage adjustment is needed in patients with renal impairment not requiring hemodialysis.

Creatinine Clearance (mL/min)
Dosage modification
50 - 80
No adjustment
15 - 50
Pharmacokinetics appear similar. No clinical data available. Treat with caution and monitor patient carefully
<15
No clinical data available. Discontinue.

 


Dosage in the Elderly

No specific dose adjustment recommended in elderly patients, but they are more at risk for severe toxicity, including myelosuppression, infection and cardiac effects.


 
F - Adverse Effects

Refer to cabazitaxel, prednisone product or drug monograph(s) for additional details of adverse effects.


Common (25-49%)

Less common (10-24%)

Uncommon (< 10%),

but may be severe or life-threatening

  • Diarrhea (may be severe)
  • Myelosuppression +/- infection, bleeding (may be severe)
  • Fatigue
  • Nausea, vomiting
  • Constipation
  • Anorexia
  • Musculoskeletal pain
  • Steroid effects (weight gain, myopathy, hyperglycemia, GI irritation)

 

  • Arrhythmia/QT prolongation, atrial fibrillation
  • Venous thromboembolism
  • Nephrotoxicity
  • Hypersensitivity
  • Cardiotoxicity
  • GI obstruction, perforation
  • Pneumonitis/ILD/ARDS
  • Increased LFTs
  • Hypotension
 
G - Interactions

Refer to cabazitaxel, prednisone drug or product monograph(s) for additional details


  • Drug interactions with therapeutic doses of cabazitaxel and co-administration of CYP3A4 substrates are not expected.
  • CYP3A4 inducers may increase cabazitaxel metabolism; avoid strong inducers
  • CYP3A4 inhibitors may reduce cabazitaxel metabolism; avoid strong inhibitors, including grapefruit juice and related products.
  • Cabazitaxel may inhibit OATP1B1 at clinically relevant doses. Avoid or separate cabazitaxel and OATP1B1 substrate administration.
 
H - Drug Administration and Special Precautions

Refer to cabazitaxel, prednisone drug or product monograph(s) for additional details


Administration

Cabazitaxel:

  • Use non-PVC equipment for preparation and administration, as cabazitaxel contains polysorbate 80 that increases the rate of di-(2-ethylhexyl) phtalate extraction (DEHP) from polyvinyl chloride (PVC).  Also do not use polyurethane equipment.
  • Use a 0.22 micron in-line filter.
  • Dilute concentrate solution with the entire contents of the supplied diluent. The concentrate-diluent solution should be further diluted immediately with either 5% dextrose or 0.9% sodium chloride solution.
  • The final concentration of the infusion solution should be 0.1mg/mL-0.26mg/mL. Infuse IV over 1 hour at room temperature.
  • Gently rotate the IV bag prior to rotating to ensure proper mixing
  • Do not mix with other drugs.  Crystallized infusion solutions should not be used.
  • Store the unopened vials at room temperature (15°C- 30°C). Do not refrigerate.
  • Final diluted solution for infusion may be stored up to 8 hours at room temperature or 48 hours under refrigeration (including 1 hour infusion time).
     

Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.
 

Prednisone:

  • Take with food in the morning at about the same time each day
  • If a dose is missed, skip that dose and continue with regular dosing the following day
     

Contraindications

  • Patients who have hypersensitivities to this drug or any of its components, including other drugs formulated with polysorbate 80
  • with neutrophil counts of ≤1.5 x 109/L
  • severe hepatic impairment (total bilirubin > 3 x ULN)
  • concomitant use of yellow fever vaccines or other live vaccines


Other Warnings/Precautions

  • Exercise caution in patients with anemia and those most at risk of developing gastrointestinal complications: patients with neutropenia, with a prior history of pelvic radiotherapy, GI disease (e.g. ulceration, bleeding), the elderly, concomitant use of NSAIDs, anti-platelet therapy or anti-coagulants.
     

Pregnancy/Lactation

  • Cabazitaxel may harm the unborn baby if pregnancy is possible in female partners of male patients.
  • Adequate contraception should be used by both sexes during treatment and for 6 months after the last dose.
  • Fertility effects have been documented in animals. Men are advised to seek advice on conservation of sperm prior to treatment.
 
I - Recommended Clinical Monitoring

Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.

Recommended Clinical Monitoring

  • CBC; baseline, on a weekly basis during cycle 1, before each treatment cycle, in patients with symptoms of anemia, and as indicated
  • Liver and renal function tests; Baseline and before each cycle
  • Clinical toxicity assessment for infusion reactions, GI effects, infection, hypersensitivity, bleeding, anemia, respiratory effects, peripheral neuropathy, thromboembolism; At each visit
  • Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version


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J - Administrative Information

Approximate Patient Visit
2 hours
Pharmacy Workload (average time per visit)
27.184 minutes
Nursing Workload (average time per visit)
38.083 minutes
 
K - References

Cabazitaxel drug monograph, Cancer Care Ontario.

de Bono J.S, Oudard S, Ozguroglu M et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010; 376: 1147–54.

Eisenberger M, Hardy-Bessard AC, Kim CS, et al.  Phase III study comparing a reduced dose of cabazitaxel (20 mg/m2) and the currently approved dose (25 mg/m2) in post-docetaxel patients with metastatic castration-resistant prostate cancer-PROSELICA. J Clin Oncol 2017;35(28):3198-206.


November 2019 Updated Premedications and Supportive Measures, Dose Modifications and Drug Administration and Special Precautions sections.


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M - Disclaimer

Regimen Abstracts
A Regimen Abstract is an abbreviated version of a Regimen Monograph and contains only top level information on usage, dosing, schedule, cycle length and special notes (if available). It is intended for healthcare providers and is to be used for informational purposes only. It is not intended to constitute or be a substitute for medical advice, and all uses of the Regimen Abstract are subject to clinical judgment. Such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability, and Cancer Care Ontario disclaims all liability for the use of this information, and for any claims, actions, demands or suits that arise from such use.
Information in regimen abstracts is accurate to the extent of the ST-QBP regimen master listings, and has not undergone the full review process of a regimen monograph.  Full regimen monographs will be published for each ST-QBP regimen as they are developed.
Regimen Monographs
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.