To see all protocols that comply with the WHO Essential Medicine List 
  1. Home
  2. Medical oncology
  3. Urogenital
  4. Prostate

Prostate metastatic cabazitaxel three weekly and prednisolone

 Ranitidine recall:

The TGA has suspended the registration of all ranitidine medicines. Further information is available from the TGA safety alert. Ranitidine is included as a default premedication in eviQ protocols and alternative approaches should be considered based on assessment of individual patients, institutional policy and availability of alternative drugs [e.g. famotidine - see ID 3264 Premedication for prophylaxis of taxane hypersensitivity reactions (infusion related reactions and anaphylaxis)]. Refer to BOPA Position Statement - H2 antagonists in paclitaxel pre-medication regimens for more information.

Check for clinical trials in this patient group. Link to Australian Clinical Trials website

The anticancer drug(s) in this protocol have been updated with the ADDIKD guideline recommendations (if applicable). Recommendations may differ from other protocols which have not been updated. For further information refer to the dedicated eviQ ADDIKD guideline webpage.

On this page
Expand all Collapse all Back to top

Cycle 1 and further cycles

Drug Dose Route Day
Cabazitaxel 20 mg/m2 IV infusion 1
Prednisolone * 10 mg ONCE a day PO 1 to 21

* prednisolone is given continuously during all cycles of treatment. This is often tapered off slowly over a period of 1 month after completion of chemotherapy at the discretion of the medical officer.

Starting cabazitaxel dose has been reduced to 20mg/m2 following the publication of the PROSELICA r study. This study reported similar progression-free and overall survival with both doses, with reduced toxicity using the lower dose. However the higher dose of 25mg/m2 was associated with a higher PSA response rate, and may be considered in select young, healthy and fit patients where response is important.

Frequency:
21 days 
Cycles:
Continuous until disease progression or unacceptable toxicity
Notes:

Patients had their luteinising hormone-releasing hormone (LHRH) agonist therapy continued.r

Concomitant use of bisphosphonate therapy was allowed if the dose had been stable for 12 weeks prior to enrolment in the study.r Bone modifying agents (e.g. zoledronic acid or denosumab) should be considered in patients with recurrent metastatic prostate cancer since it may prevent skeletal-related events and improve bone mineral density.

Drug status:

Cabazitaxel is PBS authority

Cost:
~ $160 per cycle "How this cost is calculated"

The cost displayed on the protocol is intended as rudimentary guide only for the Australian context.

The cost includes anti-cancer drugs only (not antiemetics, supportive medications or consumables), unless otherwise indicated.

Drug unit costs are taken directly from the Pharmaceutical Benefits Scheme (PBS) website (www.pbs.gov.au), MIMS Online and other sources. These costs are reviewed and updated on eviQ at 6 monthly intervals.

Where there are differing unit costs based on vial sizes and tablet strengths, the mean unit cost is used. The cost of oral continuous therapy is based on a 28 day month.

The protocol cost is derived from drug dose calculations based upon a default body surface area (BSA) of 1.8 m2; weight of 75 kg; and creatinine clearance of 75 mL/min.

One off loading doses and ongoing maintenance doses are not included in protocol cost calculations.

The cost displayed is the actual drug cost and does not necessarily reflect the cost incurred by the patient as many anti-cancer drugs are reimbursed on the PBS.

The supportive therapies (e.g. antiemetics, premedications, etc.), infusion times, diluents, volumes and routes of administration, if included, are listed as defaults. They may vary between institutions and can be substituted to reflect individual institutional policy.

Antiemetics if included in the treatment schedule are based upon recommendations from national and international guidelines. These are defaults only and may be substituted to reflect individual institutional policy. Select here for recommended doses of alternative antiemetics.

Cycle 1 and further cycles

Day 1
Dexamethasone 8 mg (PO) 60 minutes before chemotherapy
Loratadine 10 mg (PO) 60 minutes before chemotherapy
Ranitidine 150 mg (PO) 60 minutes before chemotherapy
Cabazitaxel 20 mg/m2 (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes (in non-PVC containers only)
Prednisolone 10 mg (PO) ONCE a day with or after food. Prednisolone is given continuously during all cycles of treatment. This is often tapered off slowly over a period of 1 month after completion of chemotherapy at the discretion of the medical officer.
Day 2 to 21
Prednisolone 10 mg (PO) ONCE a day with or after food. Prednisolone is given continuously during all cycles of treatment. This is often tapered off slowly over a period of 1 month after completion of chemotherapy at the discretion of the medical officer.

Starting cabazitaxel dose has been reduced to 20mg/m2 following the publication of the PROSELICA r study. This study reported similar progression-free and overall survival with both doses, with reduced toxicity using the lower dose. However the higher dose of 25mg/m2 was associated with a higher PSA response rate, and may be considered in select young, healthy and fit patients where response is important.

Frequency:
21 days 
Cycles:
Continuous until disease progression or unacceptable toxicity

Cycle 1 and further cycles

Drug Dose Route Day
Cabazitaxel 20 mg/m2 IV infusion 1
Prednisolone * 10 mg ONCE a day PO 1 to 21

* prednisolone is given continuously during all cycles of treatment. This is often tapered off slowly over a period of 1 month after completion of chemotherapy at the discretion of the medical officer.

Starting cabazitaxel dose has been reduced to 20mg/m2 following the publication of the PROSELICA r study. This study reported similar progression-free and overall survival with both doses, with reduced toxicity using the lower dose. However the higher dose of 25mg/m2 was associated with a higher PSA response rate, and may be considered in select young, healthy and fit patients where response is important.

Frequency:
21 days 
Cycles:
Continuous until disease progression or unacceptable toxicity
Notes:

Patients had their luteinising hormone-releasing hormone (LHRH) agonist therapy continued.r

Concomitant use of bisphosphonate therapy was allowed if the dose had been stable for 12 weeks prior to enrolment in the study.r Bone modifying agents (e.g. zoledronic acid or denosumab) should be considered in patients with recurrent metastatic prostate cancer since it may prevent skeletal-related events and improve bone mineral density.

Drug status:

Cabazitaxel is PBS authority

Cost:
~ $160 per cycle "How this cost is calculated"

The cost displayed on the protocol is intended as rudimentary guide only for the Australian context.

The cost includes anti-cancer drugs only (not antiemetics, supportive medications or consumables), unless otherwise indicated.

Drug unit costs are taken directly from the Pharmaceutical Benefits Scheme (PBS) website (www.pbs.gov.au), MIMS Online and other sources. These costs are reviewed and updated on eviQ at 6 monthly intervals.

Where there are differing unit costs based on vial sizes and tablet strengths, the mean unit cost is used. The cost of oral continuous therapy is based on a 28 day month.

The protocol cost is derived from drug dose calculations based upon a default body surface area (BSA) of 1.8 m2; weight of 75 kg; and creatinine clearance of 75 mL/min.

One off loading doses and ongoing maintenance doses are not included in protocol cost calculations.

The cost displayed is the actual drug cost and does not necessarily reflect the cost incurred by the patient as many anti-cancer drugs are reimbursed on the PBS.

The supportive therapies (e.g. antiemetics, premedications, etc.), infusion times, diluents, volumes and routes of administration, if included, are listed as defaults. They may vary between institutions and can be substituted to reflect individual institutional policy.

Antiemetics if included in the treatment schedule are based upon recommendations from national and international guidelines. These are defaults only and may be substituted to reflect individual institutional policy. Select here for recommended doses of alternative antiemetics.

Cycle 1 and further cycles

Day 1
Dexamethasone 8 mg (PO) 60 minutes before chemotherapy
Loratadine 10 mg (PO) 60 minutes before chemotherapy
Ranitidine 150 mg (PO) 60 minutes before chemotherapy
Cabazitaxel 20 mg/m2 (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes (in non-PVC containers only)
Prednisolone 10 mg (PO) ONCE a day with or after food. Prednisolone is given continuously during all cycles of treatment. This is often tapered off slowly over a period of 1 month after completion of chemotherapy at the discretion of the medical officer.
Day 2 to 21
Prednisolone 10 mg (PO) ONCE a day with or after food. Prednisolone is given continuously during all cycles of treatment. This is often tapered off slowly over a period of 1 month after completion of chemotherapy at the discretion of the medical officer.

Starting cabazitaxel dose has been reduced to 20mg/m2 following the publication of the PROSELICA r study. This study reported similar progression-free and overall survival with both doses, with reduced toxicity using the lower dose. However the higher dose of 25mg/m2 was associated with a higher PSA response rate, and may be considered in select young, healthy and fit patients where response is important.

Frequency:
21 days 
Cycles:
Continuous until disease progression or unacceptable toxicity

Indications:

  • metastatic castration-resistant prostate cancer previously treated with a docetaxel-containing regimen

Cautions:

  • pre existing peripheral neuropathy
  • heavily pre treated patients
  • previous neutropenia with docetaxel
Venous access required

IV cannula (IVC) or central venous access device (CVAD) is required to administer this treatment.

Read more about central venous access device line selection
Hypersensitivity/infusion related reaction

High risk with cabazitaxel

Read more about Hypersensitivity reaction
Premedication

The product information states that premedication is required for this treatment.
Please refer to the treatment schedule for the suggested premedication regimen.
This may be substituted to reflect institutional policy.

Read more about premedication for prophylaxis of taxane hypersensitivity reactions
Emetogenicity LOW

Suggested default antiemetics have been added to the treatment schedule, and may be substituted to reflect institutional policy.

Ensure that patients also have sufficient antiemetics for breakthrough emesis:

Metoclopramide 10 mg three times a day when necessary (maximum of 30 mg/24 hours, up to 5 days) OR

Prochlorperazine 10 mg PO every 6 hours when necessary.

Read more about preventing anti-cancer therapy induced nausea and vomiting
Corticosteroids

Diabetic patients should monitor their blood glucose levels closely. To minimise gastric irritation, advise patient to take immediately after food. Consider the use of a H2 antagonist or proton pump inhibitor if appropriate.

Read more about acute short term effects from corticosteroids
Peripheral neuropathy

Assess prior to each treatment. If a patient experiences grade 3 or greater, cessation of drug is recommended; review by medical officer before commencing treatment.

Read more about peripheral neuropathy

Link to chemotherapy-induced peripheral neuropathy screening tool
Bone modifying agents

The use of a bone modifying agent (BMA) should be considered as it may prevent skeletal related events and improve bone mineral density. Bone modifying agents include bisphosphonates (e.g. zoledronic acid and pamidronate) and the monoclonal antibody denosumab.
Diarrhoea

Consider prescribing prophylactic anti-diarrhoeals (eg loperamide) to prevent treatment induced diarrhoea.

If severe diarrhoea occurs, dose reduce or discontinue cabazitaxel until condition improves or resolves.

Read more about treatment induced diarrhoea
Blood tests

FBC, EUC, eGFR, LFTs and BSL prior to each treatment and as clinically indicated. Consider monitoring nadir and reducing dose if neutropenia or diarrhoea is present.
Hepatitis B screening and prophylaxis

Routine screening for HBsAg and anti-HBc is NOT usually recommended for patients receiving this treatment.

Read more about hepatitis B screening and prophylaxis in cancer patients requiring cytotoxic and/or immunosuppressive therapy
Vaccinations

Live vaccines are contraindicated in cancer patients receiving immunosuppressive therapy and/or who have poorly controlled malignant disease.

Refer to the recommended schedule of vaccination for immunocompromised patients, as outlined in the Australian Immunisation Handbook.

Read more about COVID-19 vaccines and cancer.
Fertility and fathering a child

Cancer treatment can have harmful effects on fertility and this should be discussed with all patients of reproductive potential prior to commencing treatment. It is important that all patients of reproductive potential use effective contraception whilst on therapy and after treatment finishes. Effective contraception methods and contraception timeframe should be discussed with all patients of reproductive potential.

Read more about the effect of cancer treatment on fertility
Evidence for dose modifications is limited, and the recommendations made on eviQ are intended as a guide only. They are generally conservative with an emphasis on safety. Any dose modification should be based on clinical judgement, and the individual patient’s situation including but not limited to treatment intent (curative vs palliative), the anti-cancer regimen (single versus combination therapy versus chemotherapy versus immunotherapy), biology of the cancer (site, size, mutations, metastases), other treatment related side effects, additional co-morbidities, performance status and patient preferences.Suggested dose modifications are based on clinical trial findings, product information, published guidelines and reference committee consensus . The dose reduction applies to each individual dose and not to the total number of days or duration of treatment cycle unless stated otherwise. Non-haematological gradings are based on Common Terminology Criteria for Adverse Events (CTCAE) unless otherwise specified. Renal and hepatic dose modifications have been standardised where possible. For more information see dosing considerations & disclaimer.

Note: All dose reductions are calculated as a percentage of the starting dose.

Haematological toxicity
ANC x 109/L (pre-treatment blood test)
1.0 to less than 1.5 Delay treatment until neutrophil recovery
less than 1.0 (for longer than one week) Delay treatment until neutrophil recovery and consider reducing cabazitaxel by 20% for subsequent cycles
Febrile neutropenia Delay treatment until neutrophil recovery and consider reducing cabazitaxel by 20% for subsequent cycles
Platelets x 109/L (pre-treatment blood test)
75 to less than 100 The general recommendation is to delay, however if the patient is clinically well it may be appropriate to continue treatment; refer to treating team and/or local institutional guidelines
50 to less than 75 Delay treatment until recovery
less than 50 Delay treatment until neutrophil recovery and consider reducing cabazitaxel by 20% for subsequent cycles
Kidney dosing recommendations 
  • Suggested dose modifications are based on the International Consensus Guideline on Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD).
  • Where one or more drugs in a protocol is recommended to be avoided, consider using a clinically appropriate alternative treatment protocol instead.
  • Before dose adjusting or omitting a drug, consider treatment intent.
  • In kidney replacement therapy consult a multidisciplinary team consisting of oncology/haematology with nephrology and/or clinical pharmacology for the management of dosing. 
  • For complete information on individual drug recommendations please review the individual drug monograph in the ADDIKD guideline.
eGFR
(mL/min/1.73m2)		 Cabazitaxel Prednisolone*
≥ 60

Full dose

No dose reduction required in kidney dysfunction.

 

 

 

 

 

 

 
45 - 59

Full dose
30 - 44

Full dose
15 - 29

Full dose
< 15
(without kidney replacement therapy)

Full dose

Potential for increased risk of adverse events
* This drug was not included in the ADDIKD guideline.
Hepatic impairment
Cabazitaxel is extensively metabolized in the liver
Hepatic dysfunction
Mild, Moderate and Severe No data available
Not recommended as patients with impaired hepatic function (total bilirubin ULN or greater, or AST and/or ALT 1.5 x ULN or greater) were excluded from the clinical trial
Peripheral neuropathy
Grade 2 which is present at the start of the next cycle Delay treatment until recovery and consider reducing cabazitaxel by 20% for subsequent cycles
Grade 3 or Grade 4 Cease cabazitaxel
Diarrhoea
Grade 2 persisting diarrhoea despite fluid and electrolyte management Delay treatment until toxicity resolves to Grade 1 or less and consider reducing cabazitaxel by 20% for subsequent cycles
Grade 3 Delay treatment until toxicity resolves to Grade 1 or less and consider reducing cabazitaxel by 20% for subsequent cycles
Grade 4 Cease cabazitaxel

Drug interactions in eviQ protocols are under review and being updated to align with current literature. Further site-wide updates and changes will occur in due course. References & Disclaimer

The drug interactions shown below are not an exhaustive list. For a more comprehensive list and for detailed information on specific drug interactions and clinical management, please refer to the specific drug product information and the following key resources: 

Cabazitaxel
  Interaction Clinical management
CYP3A4 inhibitors (e.g. aprepitant, azole antifungals, clarithromycin, erythromycin, grapefruit juice, ritonavir etc.) Increased toxicity of cabazitaxel possible due to reduced clearance Avoid combination or monitor for cabazitaxel toxicity (esp. neutropenia)
CYP3A4 inducers (e.g. carbamazepine, phenytoin, phenobarbitone, rifampicin, St John’s wort etc.) Reduced efficacy of cabazitaxel possible due to increased clearance Avoid combination or monitor for decreased clinical response to cabazitaxel
Prednisolone
  Interaction Clinical management
Antidiabetic agents (e.g. insulin, glibenclamide, glicazide, metformin, pioglitazone, etc) The efficacy of antidiabetic agents may be decreased Use with caution and monitor blood glucose
Azole antifungals (e.g. fluconazole, itraconazole, ketoconazole, posaconazole) Increased toxicity of prednisolone possible due to reduced clearance Avoid combination or monitor for prednisolone toxicity
Oestrogens (e.g. oral contraceptives) Increased toxicity of prednisolone possible due to reduced clearance Avoid combination or monitor for prednisolone toxicity. Dose reduction of prednisolone may be required
Ritonavir Increased toxicity of prednisolone possible due to reduced clearance Avoid combination or monitor for prednisolone toxicity
General
  Interaction Clinical management
Warfarin Anti-cancer drugs may alter the anticoagulant effect of warfarin. Monitor INR regularly and adjust warfarin dosage as appropriate; consider alternative anticoagulant.
Direct oral anticoagulants (DOACs) e.g. apixaban, rivaroxaban, dabigatran

Interaction with both CYP3A4 and P-gp inhibitors /inducers.

DOAC and anti-cancer drug levels may both be altered, possibly leading to loss of efficacy or toxicity (i.e. increased bleeding).

Apixaban: avoid concurrent use with strong CYP3A4 and P‑gp inhibitors. If treating VTE, avoid use with strong CYP3A4 and P‑gp inducers. 

Rivaroxaban: avoid concurrent use with strong CYP3A4 and P‑gp  inhibitors.

Dabigatran: avoid combination with strong P‑gp inducers and inhibitors.

If concurrent use is unavoidable, monitor closely for efficacy/toxicity of both drugs.
Digoxin Anti-cancer drugs can damage the lining of the intestine; affecting the absorption of digoxin. Monitor digoxin serum levels; adjust digoxin dosage as appropriate.
Antiepileptics Both altered antiepileptic and anti-cancer drug levels may occur, possibly leading to loss of efficacy or toxicity. Where concurrent use of an enzyme-inducing antiepileptic cannot be avoided, monitor antiepileptic serum levels for toxicity, as well as seizure frequency for efficacy; adjust dosage as appropriate.
Also monitor closely for efficacy of the anti-cancer therapy.
Antiplatelet agents and NSAIDs Increased risk of bleeding due to treatment related thrombocytopenia. Avoid or minimise combination.
If combination deemed essential, (e.g. low dose aspirin for ischaemic heart disease) monitor for signs of bleeding.
Serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs e.g. paroxetine) and serotonin noradrenaline reuptake inhibitors (SNRIs e.g. venlafaxine) Increased risk of serotonin syndrome with concurrent use of 5-HT3 receptor antagonists (e.g. palonosetron, ondansetron, granisetron, tropisetron, dolasetron, etc.) Avoid combination.
If combination is clinically warranted, monitor for signs and symptoms of serotonin syndrome (e.g. confusion, agitation, tachycardia, hyperreflexia).
For more information link to TGA Medicines Safety Update
Vaccines Diminished response to vaccines and increased risk of infection with live vaccines. Live vaccines (e.g. BCG, MMR, zoster and varicella) are contraindicated in patients on immunosuppressive therapy. Use with caution in patients on non-immunosuppressive therapy.
For more information; refer to the recommended schedule of vaccination for cancer patients, as outlined in the Australian Immunisation Handbook

eviQ provides safe and effective instructions on how to administer cancer treatments. However, eviQ does not provide every treatment delivery option, and is unable to provide a comprehensive list of cancer treatment agents and their required IV line giving set/filter. There may be alternative methods of treatment administration, and alternative supportive treatments that are also appropriate. Please refer to the individual product information monographs via the TGA website for further information.

Day 1

Approximate treatment time: 90 minutes

General patient assessment prior to each day of treatment.

Any toxicity grade 2 or greater may require dose reduction, delay or omission of treatment and review by medical officer before commencing treatment.

Prime required IV lines with sodium chloride 0.9%:

  • Low sorbing IV giving set with 0.22 micron filter must be used for cabazitaxel. 
  • Attach a second IV line via a luer lock connector as close as possible to the site of injection 
    • this may be required in case of a hypersensitivity reaction. 

Insert IV cannula or access TIVAD or CVAD.

Pre treatment medication

Verify premedication taken or administer as prescribed.

Verify antiemetics taken or administer as prescribed.

Prednisolone

  • administer orally ONCE a day on days 1 to 21
  • to be taken in the morning with or immediately after food

Note: missed doses should not be replaced; if a tablet is forgotten or vomited, normal dosing should be resumed at the next scheduled dose.

Cabazitaxel 

Administer cabazitaxel (irritant):

  • via IV infusion over 60 minutes
  • observe for hypersensitivity reactions
  • flush with ~ 100 mL of sodium chloride 0.9%.

Stop infusion at first sign of reaction:

  • if symptoms are mild and resolve when infusion is stopped, consider recommencing infusion after review by medical officer at a slower rate.
  • for severe reactions seek medical assistance immediately and do not restart infusion.

Remove IV cannula and/or deaccess TIVAD or CVAD. 

Continue safe handling precautions until 7 days after completion of drug(s)

Discharge information

Premedication
  • Premedication for next cycle of chemotherapy.
Prednisolone tablets
  • Prednisolone tablets with written instructions on how to take them.
Antiemetics
  • Antiemetics as prescribed.
Antidiarrhoeals
  • Antidiarrhoeals as prescribed.
Patient information
  • Ensure patient receives patient information sheet.

The side effects listed below are not a complete list of all possible side effects for this treatment. Side effects are categorised into the approximate onset of presentation and should only be used as a guide.

Immediate (onset hours to days)
Hypersensitivity reaction

Anaphylaxis and infusion related reactions can occur with this treatment.

Read more about hypersensitivity reaction 
Nausea and vomiting

Read more about prevention of treatment induced nausea and vomiting
Taste and smell alteration

Read more about taste and smell changes

Early (onset days to weeks)
Neutropenia

Abnormally low levels of neutrophils in the blood. This increases the risk of infection. Any fever or suspicion of infection should be investigated immediately and managed aggressively. 

Read more about immediate management of neutropenic fever
Thrombocytopenia

A reduction in the normal levels of functional platelets, increasing the risk of abnormal bleeding.  

Read more about thrombocytopenia
Anorexia

Loss of appetite accompanied by decreased food intake.

Read more about anorexia
Diarrhoea

Read more about treatment induced diarrhoea
Constipation
Skin rash

Anti-cancer drugs can cause a number of changes in the skin with maculo-papular rash the most common type of drug-induced skin reaction. 

Read more about skin rash
Arthralgia and myalgia

Generalised joint pain or and/or stiffness and muscle aches, often worse upon waking or after long periods of inactivity. Can improve with movement. May be mild or severe, intermittent or constant and accompanied by inflammation. 

Read more about arthralgia and myalgia
Fatigue

Read more about fatigue
Side effects of corticosteroids

Insomnia, oedema, increased risk of infection e.g. oral thrush, gastric irritation, worsening of peptic ulcer disease, increased blood sugar levels, loss of diabetic control, mood and behavioural changes - including anxiety, euphoria, depression, mood swings, increased appetite and weight gain, osteoporosis and fractures (long term use), bruising and skin fragility are associated with corticosteroid use.
Peripheral neuropathy

Typically symmetrical sensory neuropathy, affecting the fingers and toes, sometimes progressing to the hands and feet.  It is associated with several classes of anti-cancer drugs. These include taxanes, platinum-based compounds, vinca alkaloids and some drugs used to treat multiple myeloma.

Read more about peripheral neuropathy

Late (onset weeks to months)
Anaemia

Abnormally low levels of red blood cells (RBCs) or haemoglobin in the blood. 

Read more about anaemia
Alopecia - partial

Hair thinning and/or patchy hair loss. Patients can also experience mild to moderate discomfort of the hair follicles, and rarely pain as the hair is falling out.

Read more about alopecia and scalp cooling
Pulmonary toxicity

Pulmonary toxicity may include damage to the lungs, airways, pleura and pulmonary circulation. 

Read more about pulmonary toxicity associated with anti-cancer drugs

The evidence for this protocol comes from the results of two randomised, multicentre, multinational, phase III trials- TROPICr and PROSELICA.r

TROPICr

This trial was designed to determine whether cabazitaxel plus prednisone improves overall survival compared with mitozantrone plus prednisone in men with metastatic castration-resistant prostate cancer who had progressed after docetaxel-based chemotherapy.

Between January 2007 and October 2008, 755 patients were randomly assigned to prednisone 10mg daily with either cabazitaxel or mitozantrone intravenously on day one of each 21 day cycle for a maximum of 10 cycles.

The primary end point was overall survival (OS) and secondary endpoints included progression-free survival (PFS), PSA response, PSA progression, objective tumour response, pain response, pain progression and time to tumour progression (TTP).r

PROSELICAr

The PROSELICAr study, presented in abstract form at ASCO 2016, was a randomised multinational, phase III non-inferiority study comparing 20mg/m2 with 25mg/m2 of cabazitaxel plus prednisolone in patients with metastatic castrate resistant prostate cancer who had progressed after docetaxel. Between April 2011 and December 2013, 1200 patients were randomised to receive either cabazitaxel 20mg/m2 and prednisolone (n=598) or cabazitaxel 25mg/m2 and prednisolone (n=602).

The primary endpoint was overall survival. Secondary endpoints included progression free survival (PFS), safety, PSA, pain and tumour responses and quality of life. This data has yet to be published in a peer-review journal.

Efficacy

TROPICr

Median overall survival was 15.1 months (95% CI 14.1-16.3) in the cabazitaxel group versus 12.7 months (11.6-13.7) in the mitozantrone group.

Median progression-free survival was 2.8 months (95% CI 2.4-3.0) in the cabazitaxel group and 1.4 months (1.4-1.7) in the mitozantrone group (HR 0.74, 95% CI 0.64-0.86, p<0.0001).

Patients receiving cabazitaxel and prednisone also had higher objective tumor response rates (14.4 versus 4.4%) and PSA response rates (39.2 versus 17.8%) and longer median times to tumor progression (8.8 versus 5.4 months) and PSA progression (6.4 versus 3.1 months), but had similar times to pain progression, compared with those receiving mitozantrone and prednisone.r

There was a significant overall survival benefit and progression-free survival in the cabazitaxel group.

© Lancet 2010

PROSELICAr

Median overall survival was 13.4 months (range 12.19 to 14.88) for the cabazitaxel 20mg/m2 plus prednisolone group compared with 14.5 months (range 13.47 to 15.28) for the cabazitaxel 25mg/m2 plus prednisolone group, upper limit of 98.89% confidence interval (CI) 1.184. The study reached its non-inferiority endpoint. The PSA and ORR were slightly higher in the group receiving cabazitaxel 25mg/m2.

Outcome C20 N=598 C25 N=602 C20 v C25
Median OS, mos 13.4 (12.19 to 14.88) 14.5 (13.47 to 15.28) Upper limit of 98.89% Confidence Interval (CI): 1.184
Median PFS, mos 2.9 (2.79 to 3.45) 3.5 (3.12 to 3.94) HR (95% CI): 1.099 (0.974 to 1.24)
PSA response, % 29.5 (25.6 to 33.3) 42.9 (38.8 to 47.1) P>0.0001
ORR, n/N 50/271 18.5% 60/256 23.4%  

Toxicity

The cabazitaxel regimen was significantly more toxic than mitozantrone. The most common toxic effects of cabazitaxel were haematological and the most common non-haematological adverse event was diarrhoea. Higher frequencies of severe (grade 3 or greater) neutropenia (82 versus 58%), severe febrile neutropenia (7 versus 1%), diarrhoea (47 versus 11%, severe in 6 versus less than 1%), and peripheral neuropathy (13 versus 3%) were observed in patients receiving cabazitaxel and prednisone compared with those receiving mitozantrone and prednisone.r

The mitozantrone group had a 74% incidence of total deaths during the study which was higher compared to cabazitaxel which had an occurrence of 61%. However, patients in the cabazitaxel group had a higher risk of death of 5% within 30 days of the last drug dose than the mitozantrone group which had a 2% occurrence. Disease progression was the most common cause of early death among patients receiving mitozantrone, whereas adverse reactions, including neutropenic complications and renal failure, were the most frequent causes of early death among patients receiving cabazitaxel.r

© Lancet 2010

PROSELICAr

Grade 3-4 adverse events were less in the group receiving cabazitaxel 20 mg/m2 39.7% compared with 54.5% for those in the group receiving 25mg/m2. Grade 4 neutropaenia was less in the groups receiving 20mg/m2 than those receiving 25mg/m221.3% and 48.6% respectively and neutropaenic infection/sepsis was 2.2% and 6.1%.

[%id%]
[%title%]
[%abstract%]

Flinders Filters has partnered with eviQ to build reliable, robust search filters to retrieve core high level evidence on topics of significance to eviQ. The project goal is the provision of a sustainable model for evidence retrieval to ensure ongoing currency of content.

These search filters have been developed to retrieve the most up to date evidence from PubMed, in real time, using specifically designed search filters built to meet our needs.

Searches can be used when a protocol is scheduled for review or at any time you choose. Please click on the Specific, Balanced and Sensitive tabs below to access the Pubmed searches.

Specific Balanced Sensitive
restricted to retrieving randomised control trials and systematic reviews.

is the middle ground between sensitive and specific searches.

retrieves all clinically relevant evidence - generally a broader search on a given topic.

Access Flinders Filters, a division of the Flinders Digital Health Research Centre at Flinders University to read more about research solutions to searching problems.

Troubleshooting

Occasionally the searches may not display correctly or take too long to load (and will eventually timeout). This may be caused by Internet Explorer being unable to handle long URL's. You can rectify this by using Firefox, Safari or Google chrome. It is always a good idea to clear the cache regularly to ensure you are getting the most up to date search.

Feedback

If you identify any new articles that you believe should be included in the content, please use the feedback button below to inform us of the name of the article(s). 

Version 5

Date Summary of changes
27/07/2023

Protocol updated with ADDIKD guideline recommendations. New kidney dosing recommendation table added to dose modification section.

PDF of previous protocol.

Version number changed to V.5.

Version 4

Date Summary of changes
16/11/2021 Pulmonary toxicity added to side effects. Version number changed to V.4.

Version 3

Date Summary of changes
30/11/2012 New protocol taken to Medical Oncology Reference Committee meeting.
16/05/2013 Approved and published on eviQ.
09/05/2014 Reviewed by Medical Oncology Reference Committee electronically. No changes. PHC view removed. Review 2 years.
18/10/2016 Cabazitaxel dose changed to 20 mg/m2 based on the PROSELICA study.
GCSF removed as not PBS for indication. Evidence updated.
31/05/2017

Transferred to new eviQ website. Protocol version number changed to V.2.

  • updated note on the dose reduction to 20 mg/m2 as per reference committee consensus
  • removed "up to 10 cycles" as per reference committee consensus
  • Hepatitis screening changed to not recommended.
10/05/2018 Haematological dose modifications updated as per consensus of the expert clinician group. Version number changed to V.3.
25/03/2019 Protocol reviewed at Medical Oncology Reference Committee meeting on 15/03/2019. No changes. Next review in 5 years.
17/04/2020 "Ranitidine recall" flag added.

The information contained in this protocol is based on the highest level of available evidence and consensus of the eviQ reference committee regarding their views of currently accepted approaches to treatment. Any clinician (medical oncologist, haematologist, radiation oncologist, medical physicist, radiation therapist, pharmacist or nurse) seeking to apply or consult this protocol is expected to use independent clinical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. While eviQ endeavours to link to reliable sources that provide accurate information, eviQ and the Cancer Institute NSW do not endorse or accept responsibility for the accuracy, currency, reliability or correctness of the content of linked external information sources. Use is subject to eviQ’s disclaimer available at www.eviQ.org.au

Send feedback for this page

First approved:
Last reviewed:
Review due:

The currency of this information is guaranteed only up until the date of printing, for any updates please check:

https://www.eviq.org.au/p/1415

04 Dec 2023