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Non small cell lung cancer locally advanced or metastatic cARBOplatin and weekly PACLitaxel

This protocol was published over 10 years ago and has been assessed by the reference committee as suitable to be reviewed as required. The review due date has been removed. If something in this protocol requires reference committee consideration, please click on the feedback button at the bottom of the page.

Read more about the as required review process in this factsheet.

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Cycle 1 to 4

Drug Dose Route Day
PACLitaxel 90 mg/m2 IV infusion 1, 8, 15
cARBOplatin 6 AUC * IV infusion 1

Patients unable to tolerate full dose (for example ECOG 2/comorbidities) should receive a starting dose of carboplatin 5 AUC and paclitaxel 80 mg/m2.

*If estimated GFR is >125 mL/min (i.e. AUC 6 dose >900 mg), obtaining direct measurement rather than an estimated kidney function is strongly recommended

Frequency:
28 days 
Cycles:
4 unless otherwise indicated
Notes:

Consider combination immunotherapy chemotherapy regimens in patients with ECOG 0-1 and no contraindications.

Drug status:

All drugs in this protocol are on the PBS general schedule opens in a new tab or window

Cost:
~ $270 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

Day 1
Loratadine 10 mg (PO) 60 minutes before chemotherapy
Dexamethasone 8 mg (PO) 60 minutes before chemotherapy
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)
PACLitaxel 90 mg/m2 (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes

(in non-PVC containers only)
cARBOplatin 6 AUC (IV infusion) in 500 mL glucose 5% over 30 to 60 minutes (if estimated GFR is > 125 mL/min (i.e. 6 AUC dose > 900 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, with or after food
PACLitaxel 90 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 90 mg/m2 (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes

(in non-PVC containers only)

Cycle 2

Day 1
Loratadine 10 mg (PO) 60 minutes before chemotherapy
Dexamethasone 8 mg (PO) 60 minutes before chemotherapy
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)
PACLitaxel 90 mg/m2 (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes

(in non-PVC containers only)
cARBOplatin 6 AUC (IV infusion) in 500 mL glucose 5% over 30 to 60 minutes (if estimated GFR is > 125 mL/min (i.e. 6 AUC dose > 900 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 and 15
Metoclopramide 10 mg (PO)

one tablet when necessary (maximum of 30 mg/24 hours, up to 5 days)
PACLitaxel 90 mg/m2 (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes

(in non-PVC containers only)

Cycle 3 and 4

Day 1
Dexamethasone 8 mg (PO) 60 minutes before chemotherapy
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)
PACLitaxel 90 mg/m2 (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes

(in non-PVC containers only)
cARBOplatin 6 AUC (IV infusion) in 500 mL glucose 5% over 30 to 60 minutes (if estimated GFR is > 125 mL/min (i.e. 6 AUC dose > 900 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 and 15
Metoclopramide 10 mg (PO)

one tablet when necessary (maximum of 30 mg/24 hours, up to 5 days)
PACLitaxel 90 mg/m2 (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes

(in non-PVC containers only)

* Link to ID 7 Prevention of anti-cancer therapy induced nausea and vomiting

Frequency:
28 days 
Cycles:
4 unless otherwise indicated

Cycle 1 to 4

Drug Dose Route Day
PACLitaxel 90 mg/m2 IV infusion 1, 8, 15
cARBOplatin 6 AUC * IV infusion 1

Patients unable to tolerate full dose (for example ECOG 2/comorbidities) should receive a starting dose of carboplatin 5 AUC and paclitaxel 80 mg/m2.

*If estimated GFR is >125 mL/min (i.e. AUC 6 dose >900 mg), obtaining direct measurement rather than an estimated kidney function is strongly recommended

Frequency:
28 days 
Cycles:
4 unless otherwise indicated
Notes:

Consider combination immunotherapy chemotherapy regimens in patients with ECOG 0-1 and no contraindications.

Drug status:

All drugs in this protocol are on the PBS general schedule opens in a new tab or window

Cost:
~ $270 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

Day 1
Loratadine 10 mg (PO) 60 minutes before chemotherapy
Dexamethasone 8 mg (PO) 60 minutes before chemotherapy
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)
PACLitaxel 90 mg/m2 (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes

(in non-PVC containers only)
cARBOplatin 6 AUC (IV infusion) in 500 mL glucose 5% over 30 to 60 minutes (if estimated GFR is > 125 mL/min (i.e. 6 AUC dose > 900 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, with or after food
PACLitaxel 90 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 90 mg/m2 (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes

(in non-PVC containers only)

Cycle 2

Day 1
Loratadine 10 mg (PO) 60 minutes before chemotherapy
Dexamethasone 8 mg (PO) 60 minutes before chemotherapy
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)
PACLitaxel 90 mg/m2 (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes

(in non-PVC containers only)
cARBOplatin 6 AUC (IV infusion) in 500 mL glucose 5% over 30 to 60 minutes (if estimated GFR is > 125 mL/min (i.e. 6 AUC dose > 900 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 and 15
Metoclopramide 10 mg (PO)

one tablet when necessary (maximum of 30 mg/24 hours, up to 5 days)
PACLitaxel 90 mg/m2 (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes

(in non-PVC containers only)

Cycle 3 and 4

Day 1
Dexamethasone 8 mg (PO) 60 minutes before chemotherapy
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)
PACLitaxel 90 mg/m2 (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes

(in non-PVC containers only)
cARBOplatin 6 AUC (IV infusion) in 500 mL glucose 5% over 30 to 60 minutes (if estimated GFR is > 125 mL/min (i.e. 6 AUC dose > 900 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 and 15
Metoclopramide 10 mg (PO)

one tablet when necessary (maximum of 30 mg/24 hours, up to 5 days)
PACLitaxel 90 mg/m2 (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes

(in non-PVC containers only)

* Link to ID 7 Prevention of anti-cancer therapy induced nausea and vomiting

Frequency:
28 days 
Cycles:
4 unless otherwise indicated
  • locally advanced, recurrent or metastatic non small cell lung cancer
    • fit patients aged 70 to 89 years with ECOG performance status of 0 to 2 (consider comorbidities in ECOG 2 patients)
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
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
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.
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.
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 fetal 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 opens in a new tab or window
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.
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 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

Note: If treatment needs to be delayed on Day 8 or 15, treatment should be omitted rather than delayed and the next treatment planned for the scheduled date if recovered
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%
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 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

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: 2.5 hours

Pre treatment assessment

Check for adverse events during previous treatment.

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.

Prior to administration

Prime required IV lines with sodium chloride 0.9%:

  • paclitaxel requires a 0.2 or 0.22 micrometre inline filter AND either a non-polyvinyl chloride (non-PVC) OR a 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 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 and antiemetics taken or administer as prescribed, if required.

Paclitaxel

Administer paclitaxel (irritant with vesicant properties):

  • via IV infusion over 60 minutes
  • flush with ~ 100 mL of sodium chloride 0.9%
  • continuous observation for the first 30 mins and frequently thereafter to monitor for hypersensitivity reactions, these are more common during the first 2 cycles within the first 30 minutes.
 Infusion-related reaction (IRR)

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

Grade 1 or 2:
  • 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
  • give any further doses with close monitoring 
  • 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.

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.

Post administration

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

Pre treatment assessment

Check for adverse events during previous treatment.

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.

Prior to administration

Prime required IV lines with sodium chloride 0.9%:

  • paclitaxel requires a 0.2 or 0.22 micrometre inline filter AND either a non-polyvinyl chloride (non-PVC) OR a 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 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 and antiemetics taken or administer as prescribed, if required.

Paclitaxel

Administer paclitaxel (irritant with vesicant properties):

  • via IV infusion over 60 minutes
  • flush with ~ 100 mL of sodium chloride 0.9%
  • continuous observation for the first 30 mins and frequently thereafter to monitor for hypersensitivity reactions, these are more common during the first 2 cycles within the first 30 minutes.
 Infusion-related reaction (IRR)

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

Grade 1 or 2:
  • 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
  • give any further doses with close monitoring 
  • 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.

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

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

The evidence supporting this protocol is provided by a phase III, multicentre, randomised control trial. The trial involved 451 patients comparing doublet therapy (carboplatin and paclitaxel) with monotherapy (vinorelbine or gemcitabine) in elderly patients (over 70 years) with unresectable stage IV NSCLC or stage III disease unsuitable for radical radiation therapy and ECOG performance status 0-2.

Between April 2006 and December 2009, 451 patients from 61 centres in France were randomised to receive first line chemotherapy with either 4 cycles of doublet chemotherapy with carboplatin AUC 6 day 1 and 90mg/m2 paclitaxel on days 1, 8 and 15 every 4 weeks; or single agent chemotherapy with either 5 cycles of vinorelbine 25mg/m2 or gemcitabine 1150mg/m2 on days 1 and 8 every 3 weeks. The institution made the decision at the commencement of the study as to which single agent patients received. 

Most patients were fit, with only 27% recorded with an ECOG status of 2. 80% of participants had an activities of daily living score of 6 and 75%, had Charlson comorbidity index scores of 2 or lower, thus the results cannot be extrapolated to non-fit elderly patients with poor geriatric indices.r

The primary endpoint was overall survival (OS) with secondary endpoints being progression free survival (PFS), response to first-line therapy at 6 weeks and grade 3-4 toxicities. 

Patients who progressed or who were intolerant of treatment were withdrawn from the study and prescribed Erlotinib as second-line treatment if appropriate. 

Efficacy

Platinum-based doublet chemotherapy showed a significant improvement in 1 year survival and a reduction in risk of death in comparison to single agent chemotherapy with vinorelbine or gemcitabine in elderly patients with NSCLC.r

The results of carboplatin/ paclitaxel versus monotherapy among 451 patients evaluable for response are summarised below. Subgroup analysis showed that all histological subtypes benefitted from doublet chemotherapy over monotherapy.

 

© The Lancet 2011

Toxicity

Myelosuppression is the dose limiting toxicity of carboplatin. There were significantly more grade 3-4 haematological toxicities among the patients in the doublet chemotherapy than those in the monotherapy group.r

There were 10 treatment related deaths in the doublet chemotherapy group and 3 in the monotherapy group. Primary prophylaxis with GCSF was not recommended on the study, but was authorised as secondary prophylaxis for patients who had developed grade 3-4 neutropenia. Dose reductions of carboplatin and paclitaxel should be considered if there is clinical concern about the patients' ability to tolerate the full dose.

© The Lancet 2011

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Version 9

Date  Summary of changes
08/02/2024
  • Protocol updated with ADDIKD guideline recommendations. New kidney dosing recommendation table added to dose modification section. PDF of previous protocol.
  • Protocol assessed by eviQ medical oncology reference committee and deemed suitable to be reviewed as required. Flag added, review date removed and version number increased to V.9. Read more about as required review protocol status in this factsheet.
20/11/2024 Carboplatin dose capping note removed from detailed treatment schedule.

Version 8

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.8.

Version 7

Date Summary of changes
10/09/2020

Patient information title updated- 'weekly' added. Version number changed to V.7.

Version 6

Date  Summary of changes
08/05/2020

Title updated to include locally advanced. Treatment schedule notes updated: "Consideration needs to be given to the role of radiotherapy relative to chemotherapy for specific symptoms." and "This protocol is NOT for use with concurrent radiotherapy."- removed. "Consider combination immunotherapy chemotherapy regimens in patients with ECOG 0-1 and no contraindications."- added. Version number changed to V.6.

Version 5

Date Summary of changes
30/11/2012 Decision taken to develop protocol at Medical Oncology Reference Committee Meeting.
12/12/2013 Approved and published on eviQ.
26/08/2014 PHC view removed.
12/09/2014 Reviewed by the Medical Oncology Reference Committee. No change. Next review 2 years.
09/03/2015 Carboplatin dosing - for estimated GFR > 125 mL/min, note about measuring GFR and/or dose capping added.
08/04/2016 Reviewed by the Medical Oncology Reference Committee. No change. Next review 2 years.
31/05/2017

Transferred to new eviQ website. Version number change to V.2.

Hepatitis B screening changed to NOT recommended.

Antiemetic change: A NK1 receptor antagonist and a 5HT3 receptor antagonist in combination with dexamethasone has been added as available on the PBS for primary prophylaxis of  carboplatin induced nausea and vomiting.
10/05/2018 Haematological dose modifications updated as per consensus of the expert clinician group. Version number changed to V.3. 
23/11/2018

Protocol reviewed by Medical Oncology Reference Committee. No changes. Next review 5 years.
06/12/2018 Paclitaxel diluent changed from glucose 5% to sodium chloride 0.9%. Version change to V.4.
17/01/2019 Carboplatin AUC ≥ 4 changed from highly to moderately emetogenic as per MASCC/ESMO and ASCO guidelines and medical oncology reference committee consensus. Dexamethasone day 4 dose removed. NK1 receptor antagonist unchanged. Treatment detail and clinical information updated to reflect the change. Version number changed to V.5
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

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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/1470

08 Apr 2025