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Anal advanced cARBOplatin and PACLitaxel

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

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

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Cycle 1 to 6

Drug Dose Route Day
PACLitaxel 80 mg/m2 IV infusion 1, 8, 15
cARBOplatin 5 AUC * IV infusion 1

*If estimated GFR is greater than 125 mL/min (i.e. 5 AUC dose greater than 750 mg), obtaining direct measurement rather than an estimated kidney function is strongly recommended

Frequency:
28 days 
Cycles:
6 unless disease progression or unacceptable toxicity
Drug status:

All drugs in this protocol are on the PBS general schedule

Cost:
~ $240 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, 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

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
PACLitaxel 80 mg/m2 (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes

(in non-PVC containers only)
cARBOplatin 5 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. 5 AUC dose greater than 750 mg), obtaining direct measurement rather than an estimated kidney function is strongly recommended)
Day 2 and 3
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 8
Loratadine 10 mg (PO) 60 minutes before chemotherapy
Dexamethasone 4 mg (PO) 60 minutes before chemotherapy
PACLitaxel 80 mg/m2 (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes

(in non-PVC containers only)
Day 15
Loratadine 10 mg (PO) 60 minutes before chemotherapy
Metoclopramide 10 mg (PO)

one tablet when necessary (maximum of 30 mg/24 hours, up to 5 days)
PACLitaxel 80 mg/m2 (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes

(in non-PVC containers only)

Cycle 2

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
PACLitaxel 80 mg/m2 (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes

(in non-PVC containers only)
cARBOplatin 5 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. 5 AUC dose greater than 750 mg), obtaining direct measurement rather than an estimated kidney function is strongly recommended)
Day 2 and 3
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 8
Metoclopramide 10 mg (PO)

one tablet when necessary (maximum of 30 mg/24 hours, up to 5 days)
PACLitaxel 80 mg/m2 (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes

(in non-PVC containers only)
Day 15
Metoclopramide 10 mg (PO)

one tablet when necessary (maximum of 30 mg/24 hours, up to 5 days)
PACLitaxel 80 mg/m2 (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes

(in non-PVC containers only)

Cycle 3 to 6

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
PACLitaxel 80 mg/m2 (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes

(in non-PVC containers only)
cARBOplatin 5 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. 5 AUC dose greater than 750 mg), obtaining direct measurement rather than an estimated kidney function is strongly recommended)
Day 2 and 3
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 8
Metoclopramide 10 mg (PO)

one tablet when necessary (maximum of 30 mg/24 hours, up to 5 days)
PACLitaxel 80 mg/m2 (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes

(in non-PVC containers only)
Day 15
Metoclopramide 10 mg (PO)

one tablet when necessary (maximum of 30 mg/24 hours, up to 5 days)
PACLitaxel 80 mg/m2 (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes

(in non-PVC containers only)

* Link to Prevention of anti-cancer therapy induced nausea and vomiting (AINV)

Frequency:
28 days 
Cycles:
6 unless disease progression or unacceptable toxicity

Cycle 1 to 6

Drug Dose Route Day
PACLitaxel 80 mg/m2 IV infusion 1, 8, 15
cARBOplatin 5 AUC * IV infusion 1

*If estimated GFR is greater than 125 mL/min (i.e. 5 AUC dose greater than 750 mg), obtaining direct measurement rather than an estimated kidney function is strongly recommended

Frequency:
28 days 
Cycles:
6 unless disease progression or unacceptable toxicity
Drug status:

All drugs in this protocol are on the PBS general schedule

Cost:
~ $240 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, 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

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
PACLitaxel 80 mg/m2 (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes

(in non-PVC containers only)
cARBOplatin 5 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. 5 AUC dose greater than 750 mg), obtaining direct measurement rather than an estimated kidney function is strongly recommended)
Day 2 and 3
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 8
Loratadine 10 mg (PO) 60 minutes before chemotherapy
Dexamethasone 4 mg (PO) 60 minutes before chemotherapy
PACLitaxel 80 mg/m2 (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes

(in non-PVC containers only)
Day 15
Loratadine 10 mg (PO) 60 minutes before chemotherapy
Metoclopramide 10 mg (PO)

one tablet when necessary (maximum of 30 mg/24 hours, up to 5 days)
PACLitaxel 80 mg/m2 (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes

(in non-PVC containers only)

Cycle 2

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
PACLitaxel 80 mg/m2 (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes

(in non-PVC containers only)
cARBOplatin 5 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. 5 AUC dose greater than 750 mg), obtaining direct measurement rather than an estimated kidney function is strongly recommended)
Day 2 and 3
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 8
Metoclopramide 10 mg (PO)

one tablet when necessary (maximum of 30 mg/24 hours, up to 5 days)
PACLitaxel 80 mg/m2 (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes

(in non-PVC containers only)
Day 15
Metoclopramide 10 mg (PO)

one tablet when necessary (maximum of 30 mg/24 hours, up to 5 days)
PACLitaxel 80 mg/m2 (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes

(in non-PVC containers only)

Cycle 3 to 6

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
PACLitaxel 80 mg/m2 (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes

(in non-PVC containers only)
cARBOplatin 5 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. 5 AUC dose greater than 750 mg), obtaining direct measurement rather than an estimated kidney function is strongly recommended)
Day 2 and 3
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 8
Metoclopramide 10 mg (PO)

one tablet when necessary (maximum of 30 mg/24 hours, up to 5 days)
PACLitaxel 80 mg/m2 (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes

(in non-PVC containers only)
Day 15
Metoclopramide 10 mg (PO)

one tablet when necessary (maximum of 30 mg/24 hours, up to 5 days)
PACLitaxel 80 mg/m2 (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes

(in non-PVC containers only)

* Link to Prevention of anti-cancer therapy induced nausea and vomiting (AINV)

Frequency:
28 days 
Cycles:
6 unless disease progression or unacceptable toxicity
  • Locally recurrent inoperable or metastatic anal squamous carcinoma
  • ECOG performance status 0 to 2
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 paclitaxel

High risk with 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 for paclitaxel recommends a higher dose of dexamethasone to be used. However, many clinicians use a reducing premedication regimen with an anecdotally acceptable rate of hypersensitivity reactions (HSRs). 

Please refer to the treatment schedule for suggested premedication regimen. This may be substituted to reflect institutional policy.

Read more about premedication for prophylaxis of taxane hypersensitivity reactions (infusion related reactions and anaphylaxis)
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. 

A steroid has been included both as an antiemetic and premedication for hypersensitivity in this protocol.

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
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 2 or greater peripheral neuropathy, a dose reduction, delay, or omission of treatment may be required; review by medical officer before commencing treatment.

Read more about peripheral neuropathy

Link to Anti-cancer drug induced peripheral neuropathy screening tool
Growth factor support

G-CSF (short or long-acting) is available on the PBS for chemotherapy induced neutropenia depending on clinical indication and/or febrile neutropenia risk.  

Access the PBS website
Blood tests

FBC, EUC, eGFR and LFTs at baseline and prior to each cycle. Repeat FBC prior to each treatment. 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.

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, pregnancy and lactation

Cancer treatment can have harmful effects on fertility and this should be discussed with all patients of reproductive potential prior to commencing treatment. There is a risk of foetal harm in pregnant women. A pregnancy test should be considered prior to initiating treatment in females of reproductive potential if sexually active. It is important that all patients of reproductive potential use effective contraception whilst on therapy and after treatment finishes. Effective contraception methods and adequate contraception timeframe should be discussed with all patients of reproductive potential. Possibility of infant risk should be discussed with breastfeeding patients.

Read more about the impact 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.
  • If treatment needs to be delayed on Day 8 or 15, treatment to be omitted and the next treatment planned for the scheduled date if recovered. 
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 paclitaxel and carboplatin by 25% for subsequent cycles
Febrile neutropenia or previous delay for myelosuppression Delay treatment until recovery and consider reducing paclitaxel and carboplatin by 25% for subsequent cycles
Prolonged recovery greater than two weeks delay or 3rd delay for myelosuppression Delay treatment until recovery and consider reducing paclitaxel and carboplatin by 50% for subsequent cycles or cease
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 recovery and consider reducing paclitaxel and carboplatin by 25% 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)		 Carboplatin Paclitaxel
≥ 60

Target AUC using Calvert formula

Full dose
45 - 59

Target AUC using Calvert formula

Increased risk of adverse events*

Full dose  
30 - 44

Target AUC using Calvert formula

Increased risk of adverse events*

Full dose 
15 - 29

Target AUC using Calvert formula

Increased risk of adverse events*

Full dose
< 15
(without kidney replacement therapy)

Consult a multidisciplinary team consisting of oncology/haematology with nephrology and/or clinical pharmacology for the management of dosing. 

Full dose

Potential for increased risk of adverse events

* 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
Hepatic dysfunction
Mild Reduce paclitaxel by 25%
Moderate Reduce paclitaxel by 50%
Severe Omit paclitaxel
Peripheral neuropathy
Grade 2 which is present at the start of the next cycle Reduce paclitaxel by 25%;
If persistent, reduce paclitaxel by 50%
Grade 3 or Grade 4 Omit paclitaxel
Mucositis and stomatitis
Grade 2 Delay treatment until toxicity has resolved to Grade 1 or less and reduce doses for subsequent cycles as follows:
1st occurrence: No dose reduction
2nd occurrence: Reduce paclitaxel and carboplatin by 25%
3rd occurrence: Reduce paclitaxel and carboplatin by 50%
4th occurrence: Omit paclitaxel and carboplatin
Grade 3 or Grade 4 Delay treatment until toxicity has resolved to Grade 1 or less and reduce doses for subsequent cycles as follows:
1st occurrence: Reduce paclitaxel and carboplatin by 50%
2nd occurrence: Omit paclitaxel and carboplatin

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: 

For more information see References & Disclaimer.

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
Paclitaxel
  Interaction Clinical management
CYP3A4 inhibitors (e.g. aprepitant, azole antifungals, clarithromycin, erythromycin, grapefruit juice, ritonavir etc.) Increased toxicity of paclitaxel possible due to reduced clearance Monitor for paclitaxel toxicity
CYP3A4 inducers (e.g. carbamazepine, phenytoin, phenobarbitone, rifampicin, St John’s wort etc.) Reduced efficacy of paclitaxel possible due to increased clearance Monitor for decreased clinical response to paclitaxel
CYP2C8 inhibitors (e.g. pazopanib, lapatinib, gemfibrozil, montelukast etc.) Increased toxicity of paclitaxel possible due to reduced clearance Monitor for paclitaxel toxicity
Metronidazole, disulfiram Intolerance reaction to alcohol content of diluent of intravenous paclitaxel Avoid combination
Doxorubicin Administration schedule can influence systemic exposure to doxorubicin Minimise by administering doxorubicin first in regimens using the combination
Cisplatin Administration schedule may influence the development of myelosuppression Minimise toxicity by administering paclitaxel first in regimens using the combination
Infliximab Reduced paclitaxel concentrations possible due to increased clearance Monitor for reduced efficacy of paclitaxel
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 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 and Australian Injectable Drugs Handbook websites for further information.

Day 1

Approximate treatment time: 2.5 hours

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 neuropathy screening tool prior to each treatment.

Prime required IV lines with sodium chloride 0.9%:

  • paclitaxel requires a 0.2 or 0.22 micrometre inline filter AND a non-polyvinyl chloride (PVC) or low-sorbing polyethylene (PE) lined giving set
  • 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 infusion-related reaction (IRR) or a hypersensitivity reaction.

Insert IV cannula or access TIVAD or CVAD.

Pre treatment medication

Verify taxane premedication taken or administer as prescribed.

Verify antiemetics taken or administer as prescribed.

Paclitaxel

Administer paclitaxel (irritant with vesicant properties):
  • via controlled IV infusion over 60 minutes
  • flush with ~ 100 mL of sodium chloride 0.9%
  • observe for hypersensitivity reactions.
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
  • hypersensitivity reactions are more common during the first 2 cycles in the first 30 minutes.

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.

Remove IV cannula and/or deaccess TIVAD or CVAD. 

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

Day 8 and 15

Approximate treatment time: 90 minutes

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 neuropathy screening tool prior to each treatment.

Prime required IV lines with sodium chloride 0.9%:

  • paclitaxel requires a 0.2 or 0.22 micrometre inline filter AND a non-polyvinyl chloride (PVC) or low-sorbing polyethylene (PE) lined giving set
  • 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 infusion-related reaction (IRR) or a hypersensitivity reaction.

Insert IV cannula or access TIVAD or CVAD.

Pre treatment medication

Verify taxane premedication taken or administer as prescribed.

Verify antiemetics taken or administer as prescribed.

Paclitaxel

Administer paclitaxel (irritant with vesicant properties):
  • via controlled IV infusion over 60 minutes
  • flush with ~ 100 mL of sodium chloride 0.9%
  • observe for hypersensitivity reactions.
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
  • hypersensitivity reactions are more common during the first 2 cycles in the first 30 minutes.

Remove IV cannula and/or deaccess TIVAD or CVAD. 

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

Discharge information

Antiemetics - as/if prescribed.

Premedication - for next cycle of chemotherapy.

Patient information

Ensure patient receives protocol 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 

Read more about premedication for prophylaxis of taxane hypersensitivity reactions
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
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
Oral mucositis

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
Diarrhoea

Read more about treatment induced diarrhoea
Fatigue

Read more about fatigue
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
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

Late (onset weeks to months)
Anaemia

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

Read more about anaemia
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) 
Nail changes

Hyperpigmentation, paronychia, onycholysis, splinter haemorrhage, pyogenic granuloma formation, subungual haematoma and subungual hyperkeratosis are some of the nail changes associated with anti-cancer drugs.   

Read more about nail toxicities
Alopecia

Hair loss may occur from all parts of the body. 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

A search of the literature did not find strong evidence to support the use of carboplatin and paclitaxel in the treatment of advanced anal cancer. The expert reference panel supported publication of the protocol on the basis of the information summarised below.

The committee was most strongly influenced by the Rao et al phase II multicentre international randomised trial InterAACT with a ‘pick the winner’ design which studied 91 patients with locally recurrent inoperable or metastatic anal squamous cell carcinoma. Between December 2013 and November 2017, 46 patients were randomised to receive cisplatin 60 mg/m² (day 1) plus fluorouracil 1000 mg/m² (days 1-4) every 21 days and 45 patients were randomised to receive carboplatin 5 AUC (day 1) plus paclitaxel 80 mg/m² (days 1, 8 and 15) every 28 days. In both arms, treatment was for 24 weeks, until disease progression, intolerable toxicity or withdrawal of consent.r​ 

There was no difference in objective response rate (ORR) between the two treatment arms, however tolerability was better in the carboplatin plus paclitaxel group with a lower rate of serious adverse effects (cisplatin plus fluorouracil 62% vs carboplatin plus paclitaxel 36%, p =0.016) and there was a trend towards better survival.r​

Source Study & year published Supports use Is the dose and regimen consistent with the protocol? Comments
Phase II trials Rao et al 2020r Yes Yes -
Case series Abbas et al 2011r Yes No Single agent paclitaxel after failure of cisplatin and 5-fluorouracil
Observational studies Kim et al 2014r Yes N/A 21-day cycle. Doses not stated
Eng et al 2012r Yes N/A Doses and regimen not stated
Guidelines Date published/revised Supports use Is the dose and regimen consistent with the protocol? Comments
NCCN May 2020 Yes Yes Listed as preferred regimen in metastatic disease
BCCA September 2012 No N/A   InterAAct trial not completed at the time of publication
CCO February 2014 No N/A
ESMO September 2014 No N/A

N/A= not available

Efficacy

Rao et al 2020 outcomesr

Cisplatin/5-FU 

n=46

Carboplatin/Paclitaxel 

n=45

 Comment 
Median overall survival (months)

12.3 

[95% CI; 9.2 - 17.7]

20 

[95% CI; 12.7 - not reached]

Was not statistically significant
Progression free survival (months)

5.7 

8.1 

Was not statistically significant
Objective response rate (partial or complete response) (%)

57

[95% CI; 39.4-73.7%]

59

[95% CI; 42.1-74.4%]

  
Stable disease (%)

20

25.6

  

QOL data was collected via questionnaire at various time points but assessment was limited due to low response rate, with a non-significant trend towards worsening in global health status score for the cisplatin plus fluorouracil group and no change from baseline in the carboplatin plus paclitaxel group at 24 weeks.r

Toxicity

Grade 3 & 4 toxicitiesr

©  J Clin Oncol 2020

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Version 3

Date Summary of changes
14/09/2023

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.3. 
8/11/2023

Protocol reviewed electronically by the Medical Oncology Reference committee. No changes. Next review in 4 years.

Version 2

Date Summary of changes
08/02/2023

As per reference committee consensus, removed:

  • Ranitidine recall flag
  • Ranitidine from treatment schedule detail.

Version number increased to V.2. 

Version 1

Date Summary of changes
23/10/2020 New protocol taken to Medical Oncology Reference Committee meeting.
06/11/2020 Approved and published on eviQ. Review 1 year.
20/01/2022 Protocol reviewed electronically by Medical Oncology Reference Committee. No changes. Next review 2 years.

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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10 Sep 2024