4420-Prostate metastatic CABAZitaxel, cARBOplatin and prednisolone

Check for clinical trials in this patient group. Link to Australian Clinical Trials opens in a new tab or window website

This protocol is based on limited evidence; refer to the evidence section of this protocol for more information.

Treatment schedule Treatment schedule

Overview
Detail

Cycle 1 and further cycles

Drug	Dose	Route	Day
Prednisolone	10 mg ONCE a day #	PO	1 to 21
CABAZitaxel	20 mg/m² ##	IV infusion	1
cARBOplatin	4 AUC *	IV infusion	1
Pegfilgrastim	6 mg	Subcut	2

# Prednisolone may be given as 5 mg TWICE daily. It is given continuously during all cycles of treatment. On day 1 of each cycle the prednisolone dose is considered optional when dexamethasone is given as a premedication. Prednisolone is often tapered off slowly over a period of 1 month after completion of chemotherapy at the discretion of the medical officer. Clinicians may wish to consider minimising use of ongoing prednisolone in castrate-resistant patients.

## It is the consensus of the reference committee to use a starting dose of 20 mg/m² of cabazitaxel (the clinical trial used a dose of 25 mg/m²of cabazitaxel).^r

*If estimated GFR is greater than 125 mL/min. (i.e. 4 AUC dose greater than 600 mg), obtaining direct measurement rather than an estimated kidney function is strongly recommended.

Frequency:: 21 days

Cycles:: Continuous until disease progression or unacceptable toxicity (continuous as per reference committee consensus, noting that the clinical trial was limited to 10 cycles)

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 opens in a new tab or window

Carboplatin is on the PBS general schedule opens in a new tab or window

Pegfilgrastim is PBS authority opens in a new tab or window dependent on clinical criteria

Cost:: ~ $180 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). These costs are reviewed and updated on eviQ at 6 monthly intervals. Anti-cancer drugs that are not included on the PBS do not have a cost included in eviQ protocols.

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.

Where oral drugs are available on the PBS for both 30- and 60-day prescriptions, the unit cost for the 30-day supply is used.

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, growth factor support 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
Netupitant	300 mg (PO)	60 minutes before chemotherapy (fixed dose preparation with palonosetron)
Palonosetron	0.5 mg (PO)	60 minutes before chemotherapy (fixed dose preparation with netupitant)
Dexamethasone	8 mg (PO)	60 minutes before chemotherapy
Loratadine	10 mg (PO)	60 minutes before chemotherapy
Ranitidine	150 mg (PO)	60 minutes before chemotherapy**
Prednisolone	10 mg (PO)	ONCE a day with or after food #
CABAZitaxel	20 mg/m² (IV infusion)	in 250 mL sodium chloride 0.9% over 60 minutes ##
cARBOplatin	4 AUC (IV infusion)	in 500 mL glucose 5% over 30 to 60 minutes (Note: if estimated GFR is greater than 125 mL/min (i.e. 4 AUC dose greater than 600 mg), obtaining direct measurement rather than an estimated kidney function is strongly recommended)

Day 2
Prednisolone	10 mg (PO)	ONCE a day with or after food #
Dexamethasone	8 mg (PO)	ONCE a day (or in divided doses) with or after food. Note: dexamethasone doses on day 2 and 3 may not be required and may be reduced or omitted at the clinicians discretion###
Pegfilgrastim	6 mg (Subcut)	Inject subcutaneously on day 2, at least 24 hours after chemotherapy

Day 3
Prednisolone	10 mg (PO)	ONCE a day with or after food #
Dexamethasone	8 mg (PO)	ONCE a day (or in divided doses) with or after food. Note: dexamethasone doses on day 2 and 3 may not be required and may be reduced or omitted at the clinicians discretion###

Day 4 to 21
Prednisolone	10 mg (PO)	ONCE a day with or after food #

**It is the consensus of the medical oncology reference committee that H2 antagonist premedication for cabazitaxel may be omitted in clinical practice, however there is no published evidence available. Clinical judgement should include assessment and monitoring of individual patients, institutional policy and availability of alternative drugs.

## It is the consensus of the reference committee to use a starting dose of 20 mg/m² of cabazitaxel (the clinical trial used a dose of 25 mg/m² of cabazitaxel). ^r

^###Link to ID 7 Prevention of anti-cancer therapy induced nausea and vomiting (AINV)

Frequency:: 21 days

Cycles:: Continuous until disease progression or unacceptable toxicity (continuous as per reference committee consensus, noting that the clinical trial was limited to 10 cycles)

Treatment schedule - Overview

Cycle 1 and further cycles

Drug	Dose	Route	Day
Prednisolone	10 mg ONCE a day #	PO	1 to 21
CABAZitaxel	20 mg/m² ##	IV infusion	1
cARBOplatin	4 AUC *	IV infusion	1
Pegfilgrastim	6 mg	Subcut	2

## It is the consensus of the reference committee to use a starting dose of 20 mg/m² of cabazitaxel (the clinical trial used a dose of 25 mg/m²of cabazitaxel).^r

*If estimated GFR is greater than 125 mL/min. (i.e. 4 AUC dose greater than 600 mg), obtaining direct measurement rather than an estimated kidney function is strongly recommended.

Frequency:: 21 days

Cycles:: Continuous until disease progression or unacceptable toxicity (continuous as per reference committee consensus, noting that the clinical trial was limited to 10 cycles)

Notes:

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

Drug status:

Cabazitaxel is PBS authority opens in a new tab or window

Carboplatin is on the PBS general schedule opens in a new tab or window

Pegfilgrastim is PBS authority opens in a new tab or window dependent on clinical criteria

Cost:: ~ $180 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). These costs are reviewed and updated on eviQ at 6 monthly intervals. Anti-cancer drugs that are not included on the PBS do not have a cost included in eviQ protocols.

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.

Where oral drugs are available on the PBS for both 30- and 60-day prescriptions, the unit cost for the 30-day supply is used.

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.

Treatment schedule - Detail

Cycle 1 and further cycles

Day 1
Netupitant	300 mg (PO)	60 minutes before chemotherapy (fixed dose preparation with palonosetron)
Palonosetron	0.5 mg (PO)	60 minutes before chemotherapy (fixed dose preparation with netupitant)
Dexamethasone	8 mg (PO)	60 minutes before chemotherapy
Loratadine	10 mg (PO)	60 minutes before chemotherapy
Ranitidine	150 mg (PO)	60 minutes before chemotherapy**
Prednisolone	10 mg (PO)	ONCE a day with or after food #
CABAZitaxel	20 mg/m² (IV infusion)	in 250 mL sodium chloride 0.9% over 60 minutes ##
cARBOplatin	4 AUC (IV infusion)	in 500 mL glucose 5% over 30 to 60 minutes (Note: if estimated GFR is greater than 125 mL/min (i.e. 4 AUC dose greater than 600 mg), obtaining direct measurement rather than an estimated kidney function is strongly recommended)

Day 2
Prednisolone	10 mg (PO)	ONCE a day with or after food #
Dexamethasone	8 mg (PO)	ONCE a day (or in divided doses) with or after food. Note: dexamethasone doses on day 2 and 3 may not be required and may be reduced or omitted at the clinicians discretion###
Pegfilgrastim	6 mg (Subcut)	Inject subcutaneously on day 2, at least 24 hours after chemotherapy

Day 3
Prednisolone	10 mg (PO)	ONCE a day with or after food #
Dexamethasone	8 mg (PO)	ONCE a day (or in divided doses) with or after food. Note: dexamethasone doses on day 2 and 3 may not be required and may be reduced or omitted at the clinicians discretion###

Day 4 to 21
Prednisolone	10 mg (PO)	ONCE a day with or after food #

## It is the consensus of the reference committee to use a starting dose of 20 mg/m² of cabazitaxel (the clinical trial used a dose of 25 mg/m² of cabazitaxel). ^r

^###Link to ID 7 Prevention of anti-cancer therapy induced nausea and vomiting (AINV)

Frequency:: 21 days

Cycles:: Continuous until disease progression or unacceptable toxicity (continuous as per reference committee consensus, noting that the clinical trial was limited to 10 cycles)

Indications and patient population

Advanced or metastatic castration-resistant prostate cancer
- ECOG performance status 0 to 2
- Consider for patients with features of aggressive variant prostate cancer clinicopathological criteria (AVPC-C) or aggressive variant prostate cancer molecular signature (AVPC-MS)

Clinical information

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 and carboplatin. Hypersensitivity risk increases with number of cycles of carboplatin. Rechallenge with carboplatin after hypersensitivity carries a high risk of anaphylaxis, and where clinically indicated, should be undertaken with a desensitisation protocol with appropriate supports in place. Refer to local institutional policy. 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 MODERATE	Suggested default antiemetics have been added to the treatment schedule, and may be substituted to reflect institutional policy. A combination of an NK1 receptor antagonist, 5HT3, and a steroid is available on the PBS for the prevention of nausea and vomiting associated with all moderate to highly emetogenic anti-cancer therapies. 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
Carboplatin dosing	Directly measured glomerular filtration rate (mGFR) is the preferred kidney function value in the Calvert formula, especially in patients with either: curative treatment intent clinical situations where estimated kidney function may be unreliable for accurate therapeutic dosing such as eGFR > 125mL/min/1.73 m² eGFR ≤ 45 mL/min/1.73 m² extremes of body size or muscle mass amputees paraplegics. In all other clinical situations, eGFR adjusted to an individual’s body surface area (BSA-adjusted eGFR) is a suitable alternative to directly mGFR for use in the Calvert formula.
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
Growth factor support	G-CSF (short or long-acting) may be available on the PBS for chemotherapy induced neutropenia depending on clinical indication and/or febrile neutropenia risk. Please refer to the PBS website opens in a new tab or window for further information.
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 at baseline and prior to each cycle. Consider monitoring nadir and reducing cabazitaxel dose if neutropenia or diarrhoea is present. Calcium and magnesium at baseline and as clinically indicated. Recalculation of carboplatin doses at each cycle is unnecessary, except when baseline kidney function (e.g., eGFR) alters by greater than 20% or when there is a change in the clinical status of the patient.
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. Possible suboptimal response to inactivated vaccines. For more information about vaccinations in people with cancer refer to the Australian Immunisation Handbook opens in a new tab or window.
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 impact of cancer treatment on fertility opens in a new tab or window

Dose modifications

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) opens in a new tab or window 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*	Refer to local institutional guidelines; it is the view of the expert clinicians that treatment should continue if patient is clinically well.
0.5 to less than 1.0	Delay treatment until recovery
less than 0.5	Delay treatment until recovery and consider reducing carboplatin by 25% and cabazitaxel by 20% for subsequent cycles
Febrile neutropenia	Delay treatment until recovery and consider reducing carboplatin by 25% and cabazitaxel by 20% for subsequent cycles
Platelets x 10⁹/L (pre-treatment blood test)
75 to less than 100	Refer to local institutional guidelines; it is the view of the expert clinicians that treatment should continue if patient is clinically well.
50 to less than 75	Delay treatment until recovery
less than 50	Delay treatment until recovery and consider reducing carboplatin by 25% and cabazitaxel by 20% for subsequent cycles

* For heavily pre-treated patients or patients treated with palliative intent, consider delaying treatment if ANC is less than 1.5 x 10⁹/L

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	Carboplatin	Prednisolone*
≥ 60	Full dose	Target AUC using Calvert formula	No dose reduction required in kidney dysfunction.
45 - 59	Full dose	Target AUC using Calvert formula Increased risk of adverse events**
30 - 44	Full dose	Target AUC using Calvert formula Increased risk of adverse events**
15 - 29	Full dose	Target AUC using Calvert formula Increased risk of adverse events**
< 15 (without kidney replacement therapy)	Full dose Potential for increased risk of adverse events	Consult a multidisciplinary team consisting of oncology/haematology with nephrology and/or clinical pharmacology for the management of dosing.
* This drug was not included in the ADDIKD guideline. ** Increased risk of haematological adverse events especially in patients with either poor performance status, extensive prior anticancer treatment, or concomitant nephrotoxic drug exposure.

Hepatic impairment
Cabazitaxel is extensively metabolised in the liver
Hepatic dysfunction
Minimal - mild	Delay treatment until ALT and/or AST returned to less than 1.5 x ULN and bilirubin to less than ULN. Consider reducing cabazitaxel by 20%
Moderate - severe	Not recommended

Note: In the trial, patients with liver metastases or acute tumour-associated illness with bilirubin and AST and/or ALT less than or equal to 4 x ULN, treatment was delayed for 2 weeks. When ALT and/or AST and/or bilirubin have returned to less than or equal to baseline values, the patient was recommenced on treatment with a lower dose.

Peripheral neuropathy
Grade 2 persistent at the start of the next cycle	Delay until recovery and consider reducing cabazitaxel by 20% for subsequent cycles
Grade 3 or Grade 4	Cease cabazitaxel

Diarrhoea
Grade 2	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

Mucositis and stomatitis
Grade 2	Delay treatment until toxicity has resolved to Grade 1 or less and reduce the dose for subsequent cycles as follows: 1^st occurrence: No dose reduction 2^ndoccurrence: Reduce carboplatin by 25% 3^rdoccurrence: Reduce carboplatin by 50% 4^thoccurrence: Omit carboplatin
Grade 3 or Grade 4	Delay treatment until toxicity has resolved to Grade 1 or less and reduce the dose for subsequent cycles as follows: 1^st occurrence: Reduce carboplatin by 50% 2^ndoccurrence: Omit carboplatin

Interactions

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:

MIMS - interactions tab opens in a new tab or window (includes link to a CYP-450 table) (login required)
Australian Medicines Handbook (AMH) – interactions tab opens in a new tab or window, tables on drugs that may prolong the QT interval opens in a new tab or window, CYP enzymes opens in a new tab or window, P-glycoprotein interactions, opens in a new tab or window and seizure risk opens in a new tab or window (login required)
Micromedex Drug Interactions opens in a new tab or window (login required)
Cancer Drug Interactions opens in a new tab or window
Cytochrome P450 Drug Interactions opens in a new tab or window

For more information see References & Disclaimer.

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

Carboplatin
	Interaction	Clinical management
Nephrotoxic drugs (e.g. aminoglycosides, amphotericin, contrast dye, frusemide, NSAIDs)	Additive nephrotoxicity	Avoid combination or monitor kidney function closely
Ototoxic drugs (e.g. aminoglycosides, frusemide, NSAIDs)	Additive ototoxicity	Avoid combination or perform regular audiometric testing
Paclitaxel	Administration schedule may influence the development of myelosuppression	Minimise toxicity by administering paclitaxel first in regimens using the combination

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

NK-1 antagonist e.g. aprepitant, fosaprepitant, netupitant
	Interaction	Clinical management
Dexamethasone	Increased effects/toxicity of dexamethasone due to inhibition of its metabolism via CYP3A4	Reduce dose of antiemetic dexamethasone by approximately 50% when adding a NK-1 antagonist. For protocols that already recommend a NK-1 antagonist, the dose reduction of antiemetic dexamethasone has already been taken into account. If dexamethasone is part of the chemotherapy protocol, dose reduction as per the product information is not routinely recommended in clinical practice and no additional dexamethasone is required for antiemetic cover.
Warfarin	Reduced anticoagulant efficacy of warfarin due to increased clearance (aprepitant induces CYP2C9). *Note interaction only applicable to aprepitant/ fosaprepitant	INR should be monitored in the 2 week period, particularly at 7 to 10 days following the administration of aprepitant/ fosaprepitant
Combined oral contraceptive	Reduced contraceptive efficacy due to increased clearance. *Note interaction only applicable to aprepitant/ fosaprepitant	Alternative non-hormonal methods should be used during and for 1 month after stopping aprepitant/ fosaprepitant
CYP3A4 inducers (e.g. carbamazepine, phenytoin, phenobarbitone, rifampicin, St John’s wort etc.)	Reduced efficacy of NK-1 antagonist possible due to increased clearance	Avoid combination or monitor for decreased antiemetic effect. Consider using an alternative antiemetic regimen
CYP3A4 inhibitors (e.g. azole antifungals, clarithromycin, erythromycin, grapefruit juice, ritonavir etc.)	Increased toxicity of NK-1 antagonist possible due to reduced clearance	Avoid combination or monitor for increased adverse effects of NK-1 antagonist (e.g. headache, hiccups, constipation)
Drugs metabolised by CYP3A4 (e.g. etoposide, imatinib, irinotecan, midazolam, paclitaxel, vinblastine, vincristine etc.)	Increased effects/toxicity of these drugs possible due to inhibition of CYP3A4 by NK-1 antagonist	Avoid combination or monitor for increased toxicity especially with orally administered drugs

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 opens in a new tab or window and P‑gp opens in a new tab or window inhibitors. If treating VTE, avoid use with strong CYP3A4 opens in a new tab or window and P‑gp opens in a new tab or window inducers. Rivaroxaban: avoid concurrent use with strong CYP3A4 opens in a new tab or window and P‑gp opens in a new tab or window inhibitors. Dabigatran: avoid combination with strong P‑gp opens in a new tab or window 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 opens in a new tab or window

Administration

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 or address chemical compatibilities related to IV drug preparation and administration. 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 opens in a new tab or window and Australian Injectable Drugs Handbook opens in a new tab or window websites for further information.

eviQ is currently updating the way information is presented in the administration section, if you notice any discrepancies please let us know, via feedback@eviq.org.au.

Day 1

Approximate treatment time: 3 hours

Safe handling and waste management

Safe administration

Pre treatment assessment

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

Anti-cancer drug patient assessment tool prior to each day of treatment.

Anti-cancer drug induced peripheral neuropathy screening tool prior to each treatment.

Prior to administration

Prime required IV lines with sodium chloride 0.9%:.

cabazitaxel requires a 0.2 or 0.22 micrometre inline filter. Do not use polyurethane (PUR) infusion sets (tubing, filter, pumps) for the administration.
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 or an infusion-related reaction (IRR).

Insert IV cannula or access TIVAD or CVAD.

Pre treatment medication

Verify taxane premedication taken or administer as prescribed.

Verify premedication/antiemetics have been taken as prescribed, see treatment schedule detail for suggested medications.

Chemotherapy - Time out

Cabazitaxel

Administer cabazitaxel (irritant):

via IV infusion over 60 minutes
flush with ~ 100 mL of sodium chloride 0.9%
observe for hypersensitivity reactions, these are more common during the first 2 cycles and can occur within the first few minutes.

Infusion-related reaction (IRR)

Stop infusion at first sign of anaphylaxis or severe IRR and manage as per emergency:

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.

Carboplatin

Administer carboplatin (irritant):

via IV infusion over 30 to 60 minutes
flush with ~100 mL of sodium chloride 0.9%.
observe for hypersensitivity reactions which can increase with the number of cycles administered and may occur within minutes of administration.

Infusion-related reaction (IRR)

Stop infusion at first sign of anaphylaxis or severe IRR and manage as per emergency.

Grade 1 or 2:

slow or hold rate of infusion, alert medical officer and monitor closely
- if symptoms are mild and resolve when infusion is stopped, consider recommencing infusion after review by medical officer at a slower rate
- administer symptomatic medications as prescribed
further doses require close monitoring, premedications should be considered and prescribed by the medical officer as per local policy.

Grade 3 or 4:

stop infusion immediately
seek urgent medical officer review, do not restart the infusion.

Prednisolone

Administer prednisolone:

orally, as per treatment schedule
to be taken 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.

Potential adverse events:

prednisolone can cause sleep disturbance, if this occurs a daily morning dose is recommended.

Post administration

Remove IV cannula and/or deaccess TIVAD or CVAD.

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

Discharge information

Discharge medications

Premedication - for next cycle of chemotherapy.

Prednisolone tablets - with written instructions on how to take them.

Antiemetics - as/if prescribed.

Antidiarrhoeals - as/if prescribed.

Growth factor support - as/if prescribed, and arrangements for administration.

Patient information

Ensure patient receives protocol patient information sheet.

Side effects

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
Bone pain	Bone pain, usually in the lower back or pelvis, associated with G-CSF.

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
Oral mucositis and stomatitis	Erythematous and ulcerative lesions of the gastrointestinal tract (GIT). It commonly develops following anti-cancer treatment, radiation therapy to the head, neck or oesophagus, and high-dose chemotherapy followed by a blood and marrow transplant (BMT). Read more about oral mucositis and stomatitis
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
Cognitive changes (chemo fog)	Changes in cognition characterised by memory loss, forgetfulness and feeling vague. This is also referred to as 'chemo brain' or 'chemo fog'. Read more about cognitive changes (chemo fog)

Evidence

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A search of the literature did not find strong evidence to support the use of cabazitaxel and carboplatin treatment in prostate cancer. The expert reference panel supported publication of the protocol on the basis of the information summarised below indicated for a subset of patients with metastatic aggressive variant type prostate cancer (AVPC).

The phase I - II, open label, randomised controlled trial by Corn et al aimed to compare the efficacy and safety of cabazitaxel alone compared to cabazitaxel with carboplatin in patients with progressive metastatic castration-resistant prostate cancer (mCRPC). Furthermore, they aimed to investigate the hypothesis that patients with clinical or molecular features of the aggressive variant prostate cancer molecular signature (AVPC-MS) would benefit more from the addition of carboplatin.^r

AVPC-MS was defined as a molecular signature of combined tumour suppressor defects (>1 alteration in TP53, RB1 and/or PTEN). Aggressive variant prostate cancer clinicopathological criteria (AVPC-C) was defined as patients with at least one of the following 7 clinical features:

histological evidence of small-cell prostate carcinoma
exclusively visceral metastases
predominantly lytic bone metastases
bulky (>5 cm) lymphadenopathy or primary tumour with Gleason score of 8 or more at diagnosis
low PSA (<10 ng/mL) plus high volume (≥20) bone metastases at initial presentation, before start of androgen deprivation therapy, or at symptomatic progression in the castrate setting
elevated (two times or more the institutional ULN) lactate dehydrogenase or carcinoembryonic antigen,
short interval response (<6 months) to androgen deprivation therapy.

Between August 2012 and May 2015, 160 patients were randomised to either cabazitaxel 25 mg/m² OR cabazitaxel 25 mg/m² plus carboplatin AUC 4 every 21 days continuously until disease progression, unacceptable toxicity or patient withdrawal; up to a maximum of 10 cycles. All patients received prednisone 10 mg daily and growth factor support.

The primary outcome was investigator assessed progression-free survival (PFS). Secondary endpoints were the evaluation of PSA response (defined as a ≥50% decline from baseline); association of change in bone-specific alkaline phosphatase and urine n-telopeptides with response, overall survival; safety and toxicity and the effect of the aggressive variant prostate cancer on response to treatment.^r

Source	Study and Year Published	Supports Use	Is the dose and regimen consistent with the protocol?	Comments
Phase II trials	Corn et al, 2019^r	Yes	No	Phase I trial - to determine maximum dose Phase II trial - carboplatin + cabazitaxel 25 mg/m² improved PFS in overall study population versus cabazitaxel monotherapy
Guidelines	Date Published	Supports Use	Is the dose and regimen consistent with the protocol?	Comments
NCCN	2024	Yes	Yes	cabazitaxel dose 20 mg/m² every 21 days, carboplatin 4 AUC
BCCA	N/A	N/A	N/A	-
CCO	2022	No	N/A	-
ESMO	2020	No	N/A	-

Efficacy

Summary of evidence

Outcome	Corn et al, 2019^r
	Cabazitaxel and Carboplatin (n=81)	Cabazitaxel (n=79)
Median follow up (months)	31	31
Median PFS (months)	7.3 (95% CI 3.5 -5.7) [HR 0.69, 95% CI 0.50-0.95, p=0.018]	4.5 (95% CI 5.5-8.2) [HR 0.69, 95% CI 0.50-0.95, p=0.018]
Median OS (months)	18.5 * (95% CI 16.7-21.9) [HR 0.89, 95% CI 0.63-1.25, p=0.5]	17.3 * (95% CI 13.8-21.9) [HR 0.89, 95% CI 0.63-1.25, p=0.5]
PSA concentrations decline of greater than fifty percent (%)	61.7 [OR 2.53, 95% CI 1.25-5.10, p=0.016]	40.9 [OR 2.53, 95% CI 1.25-5.10, p=0.016]

*Not statistically significant

Kaplan-Meier A) PFS B) OS in intent-to-treat (ITT) population ^r

Prespecified subgroup analysis showed that the combination favoured those meeting AVPC-C criteria (HR 0·58, 0·37–0·89, p=0·013), but tests for interaction were not significant in the intention-to-treat population.

In pre-planned subgroup analysis, men with AVPC-MS-positive tumours had a median PFS of 1·7 months (95% CI 1·3 to NA) when treated with cabazitaxel versus 7·5 months (95% CI 4·4–9·6) when treated with the combination (p=0·017) and an estimated median OS of 8·5 months (4·8 to NA) versus 20·2 months (13·3–37·2, p=0·0002).

Conversely, men with AVPC-MS-negative tumours treated with cabazitaxel had an estimated median PFS of 6·3 months (5·9–10·9) versus 6·5 months (3·9–8·4; p=0·38) for the combination and an estimated median OS of 21·7 months (95% CI 17·4 to NA) versus 21·5 months (9·1 to NA; p=0·702).

Toxicity

Treatment was generally well tolerated. There was a higher incidence of grade 3-4 fatigue (16% vs 9%), anaemia, (23% vs 4%), neutropenia (16% vs 4%) and thrombocytopenia (14% vs 1%) in the combination group. There were no treatment-related deaths. Adverse events leading to treatment discontinuation occurred in eight (10%) patients treated with cabazitaxel and ten (12%) in the combination group.

Adverse Events^r

References References

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Literature Search

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History

Version 1

Date	Summary of changes
03/09/2024	New protocol discussed at urogenital reference committee meeting 24/05/2024. Protocol approved on 21/08/2024, published on 03/09/2024. Review in 1 year.
10/04/2025	Cabazitaxel IV line information updated in the administration section to align with the product information, refer to manufacturer’s instructions for specific line requirements.
07/07/2025	Bone pain added to side effects.

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

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First approved:: 21 August 2024
Review due:: 31 December 2025

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/4420

13 Jul 2025