Les renseignements du Formulaire de médicaments s’adressent aux professionnels de la santé. Il ne s’agit pas d’un avis médical. Certains des renseignements, y compris ceux sur le financement des médicaments anticancéreux, ne s’appliquent pas à tous les patients. Les plans de traitement du cancer sont propres à chaque patient. Si vous êtes un patient, veuillez parler avec votre équipe soignante pour comprendre comment ces renseignements s’appliquent à vous.
CABAPRED
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.
For the treatment of metastatic castration resistant prostate cancer (mCRPC), in patients who have progressed on/after prior docetaxel-containing chemotherapy and an androgen-receptor-axis targeted agent (ARAT), regardless of the order of treatment or treatment settings. (Not funded for combination treatment with abiraterone, enzalutamide, or radium-233 for mCRPC)
(Refer to NDFP form for details.)
cabazitaxel
New Drug Funding Program
(Cabazitaxel - Metastatic Castration Resistant Prostate Cancer)
(NDFP Website
)
prednisone
ODB - General Benefit
(prednisone)
(ODB Formulary
)
|
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.
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)
Low
- Also refer to CCO Antiemetic Recommendations.
Screen for hepatitis B virus in all cancer patients starting systemic treatment. Refer to the hepatitis B virus screening and management guideline.
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)
Other supportive care:
- 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.
Doses should be modified according to the protocol by which the patient is being treated.
Patients on LHRH agonists should continue on the agents.
Use with caution in patents with hemoglobin < 10 g/dL. Hemoglobin and hematocrit should be checked prior to treatment.
Dosage with toxicity
Do not treat until ANC > 1.5 x 109/L and platelets are ≥ 100 x 109/L.
| Dose (mg/m2) | Dose (mg/m2) | |
| Starting dose | 25 | 20 |
| First reduction | 20 | 15 |
| Second reduction | 15 | Discontinue |
|
Adverse reactions / Counts |
Action |
Dose for Next Cycle* |
|
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 |
↓ 1 dose level |
|
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 |
Restart:
|
|
| 3 or 4 |
|
|
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 |
Maximum 15 (unknown efficacy; monitor carefully) |
|
>3 x ULN |
and |
any |
Contraindicated |
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
|
No adjustment.
|
|
<15; end stage renal disease
|
Limited clinical data. Treat with caution and monitor patient carefully.
|
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.
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 |
|
|
|
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.
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.
- Cabazitaxel products have different dilution instructions; refer to the respective product monograph to ensure that the appropriate instructions are followed.
- 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.
Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.
Administration: 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
- Patients with neutrophil counts of ≤1.5 x 109/L
- Patients with severe hepatic impairment (total bilirubin > 3 x ULN)
- Concomitant use of yellow fever vaccines
Other Warnings/Precautions
- Avoid use of live vaccines in patients receiving cabazitaxel. Inactivated vaccines may be administered; however, response may be diminished.
- 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.
- Patients should exercise caution when driving or operating a vehicle or potentially dangerous machinery as fatigue and dizziness have been reported.
Pregnancy/Lactation
- Cabazitaxel may cause harm to a developing fetus or lead to loss of pregnancy. Adequate contraception should be used by both sexes during treatment and for 6 months after the last dose.
- Fertility effects: Probable (cabazitaxel)
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
Refer to the hepatitis B virus screening and management guideline for monitoring during and after treatment.
Recommended Clinical Monitoring
-
CBC; Baseline, weekly during cycle 1, before each cycle, and as clinically indicated (also in patients with symptoms of anemia)
-
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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Cabazitaxel drug monograph, Ontario Health (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.
February 2023 Updated Dosage with hepatic impairment, Dosage with renal impairment, Adverse effects, and Special precautions sections
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.