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Head and neck squamous cell carcinoma recurrent or metastatic cARBOplatin and fluorouracil

 ADDIKD Carboplatin dosing:

For dosing carboplatin, ADDIKD recommends that:

  • Directly measured glomerular filtration rate (mGFR) is the preferred kidney function value in the Calvert formula​, especially where estimated kidney function may be unreliable for accurate therapeutic dosing.
  • Where mGFR is unavailable, eGFR adjusted to an individual’s body surface area (BSA-adjusted eGFR) is a suitable alternative for use in the Calvert formula.
  • Kidney function should not be capped at 125 mL/min for use in the Calvert formula.
  • Recalculation of carboplatin doses at each cycle is unnecessary, except when baseline kidney function (e.g., eGFR) alters by > 20% or when there is a change in the clinical status of the patient.

For further information refer the eviQ Factsheet around carboplatin dosing and the carboplatin drug monograph within the ADDIKD guideline. To assist with calculations, use the eviQ Estimated Glomerular Filtration Rate (eGFR) and carboplatin dose calculators.

 Fluoropyrimidine overdose or overexposure:

Fluoropyrimidine overdose or overexposure may result in severe or life-threatening toxicity. An antidote is available and is highly effective if given within 96 hours.  Read more about fluoropyrimidine overdose or overexposure.

Head and neck cancer treatment is complex and combined modality therapy is common; the involvement of a multidisciplinary team (MDT) in the initial development and ongoing evaluation of the treatment plan, and the management of the sequelae associated with treatment is recommended.

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

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

The anticancer drug(s) in this protocol may have been included in the ADDIKD guideline. Dose recommendations in kidney dysfunction have yet to be updated to align with the ADDIKD guideline. Recommendations will be updated once the individual protocol has been evaluated by the reference committee. For further information refer to the ADDIKD guideline. To assist with calculations, use the eviQ Estimated Glomerular Filtration Rate (eGFR) calculator.

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Cycle 1 and further cycles

Drug Dose Route Day
cARBOplatin 5 AUC * IV infusion 1
Fluorouracil 4,000 mg/m2 (equivalent to 1000 mg/m2/day) CIV via pump over 96 hours 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 renal function and/or dose capping is strongly recommended.

Frequency:
21 days or 28 days
Cycles:
Continuous until disease progression or unacceptable toxicity (reassess response after 2 to 3 cycles; up to 6 cycles in responding patients)
Drug status:

All drugs in this protocol are on the PBS general schedule

Cost:
~ $220 per cycle (chemotherapy only) "How this cost is calculated"

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

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

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

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

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

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

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

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

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

Cycle 1 and further cycles

Day 1
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
cARBOplatin 5 AUC (IV infusion) in 500 mL glucose 5% over 30 to 60 minutes (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 renal function and/or dose capping is strongly recommended)
Fluorouracil 4,000 mg/m2 (CIV) via ambulatory infusion pump over 96 hours (equivalent to 1000 mg/m2/day)
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 *

* Link to ID 7 Prevention of antineoplastic induced nausea and vomiting

Frequency:
21 days or 28 days
Cycles:
Continuous until disease progression or unacceptable toxicity (reassess response after 2 to 3 cycles; up to 6 cycles in responding patients)

Cycle 1 and further cycles

Drug Dose Route Day
cARBOplatin 5 AUC * IV infusion 1
Fluorouracil 4,000 mg/m2 (equivalent to 1000 mg/m2/day) CIV via pump over 96 hours 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 renal function and/or dose capping is strongly recommended.

Frequency:
21 days or 28 days
Cycles:
Continuous until disease progression or unacceptable toxicity (reassess response after 2 to 3 cycles; up to 6 cycles in responding patients)
Drug status:

All drugs in this protocol are on the PBS general schedule

Cost:
~ $220 per cycle (chemotherapy only) "How this cost is calculated"

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

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

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

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

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

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

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

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

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

Cycle 1 and further cycles

Day 1
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
cARBOplatin 5 AUC (IV infusion) in 500 mL glucose 5% over 30 to 60 minutes (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 renal function and/or dose capping is strongly recommended)
Fluorouracil 4,000 mg/m2 (CIV) via ambulatory infusion pump over 96 hours (equivalent to 1000 mg/m2/day)
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 *

* Link to ID 7 Prevention of antineoplastic induced nausea and vomiting

Frequency:
21 days or 28 days
Cycles:
Continuous until disease progression or unacceptable toxicity (reassess response after 2 to 3 cycles; up to 6 cycles in responding patients)
  • Recurrent or metastatic head and neck squamous cell carcinoma (SCC) not amenable to salvage surgery or radiation therapy
  • This protocol is favoured in patients with performance status 0 to 2 who have already had cisplatin as previous treatment
Safety alert fluoropyrimidines

Fluoropyrimidines can be administered by different routes and schedules with each method having associated increased risk of certain side effects. Fluoropyrimidine overdose or overexposure is a rare but potentially life threatening side effect of this drug class and can occur by any route of administration. An antidote is available and highly effective if given within 96 hours.

Read more about the medication safety alert for infusional fluorouracil and fluoropyrimidine overdose or overexposure
Venous access

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 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
Emetogenicity MODERATE

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

Carboplatin AUC > 4 is classified by MASCC/ESMO Antiemetic Guidelines 2016 and ASCO Antiemetic Guidelines 2017 as having moderate emetogenicity. 

However, a NK1 receptor antagonist and a 5HT3 receptor antagonist in combination with dexamethasone are available on the PBS for primary prophylaxis of carboplatin induced nausea and vomiting.

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
Cardiac toxicity

Cardiac toxicity is a serious complication that can occur during treatment with fluorouracil. Patients treated with fluorouracil, especially those with a prior history of cardiac disease or other risk factors, should be carefully monitored during therapy.

Read more about cardiac toxicity associated with anti-cancer drugs
Diarrhoea

Antidiarrhoeals (e.g. loperamide) are usually prescribed with this treatment.

Read more about treatment induced diarrhoea
Dihydropyrimidine dehydrogenase (DPD) enzyme deficiency

Rare, life-threatening toxicities such as mucositis, neutropenia, neurotoxicity and diarrhoea have been reported following administration of fluoropyrimidines (e.g. fluorouracil and capecitabine). Severe unexplained toxicities require investigation prior to continuing with treatment. Testing for DPD enzyme deficiency is available in Australia but not currently reimbursed.

Read more about dihydropyrimidine dehydrogenase (DPD) enzyme deficiency
Nutrition risk HIGH

All patients should be assessed by a dietitian prior to commencement of treatment.

Read more about COSA's evidence-based practice guidelines for the nutritional management of adult patients with head and neck cancer 
Speech pathology

All head and neck patients presenting with either a swallowing and /or communication problem should be referred
Blood tests

FBC, EUC, eGFR, and LFTs at baseline and prior to each cycle. 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 effect of cancer treatment on fertility
Evidence for dose modifications is limited, and the recommendations made on eviQ are intended as a guide only. They are generally conservative with an emphasis on safety. Any dose modification should be based on clinical judgement, and the individual patient’s situation including but not limited to treatment intent (curative vs palliative), the anti-cancer regimen (single versus combination therapy versus chemotherapy versus immunotherapy), biology of the cancer (site, size, mutations, metastases), other treatment related side effects, additional co-morbidities, performance status and patient preferences.Suggested dose modifications are based on clinical trial findings, product information, published guidelines and reference committee consensus . The dose reduction applies to each individual dose and not to the total number of days or duration of treatment cycle unless stated otherwise. Non-haematological gradings are based on Common Terminology Criteria for Adverse Events (CTCAE) unless otherwise specified. Renal and hepatic dose modifications have been standardised where possible. For more information see dosing considerations & disclaimer.
The dose recommendations in kidney dysfunction (i.e.renal impairment) displayed may not reflect those in the ADDIKD guideline and have been included for historical reference only. Recommendations will be updated once the individual protocol has been evaluated by the reference committee, with this version of the protocol then being archived. Clinicians are expected to refer to the ADDIKD guideline prior to prescribing in kidney dysfunction.
International Consensus Guideline for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD).

For dosing carboplatin, ADDIKD recommends that:

  • Directly measured glomerular filtration rate (mGFR) is the preferred kidney function value in the Calvert formula​, especially where estimated kidney function may be unreliable for accurate therapeutic dosing.
  • Where mGFR is unavailable, eGFR adjusted to an individual’s body surface area (BSA-adjusted eGFR) is a suitable alternative for use in the Calvert formula.
  • Kidney function should not be capped at 125 mL/min for use in the Calvert formula.
  • Recalculation of carboplatin doses at each cycle is unnecessary, except when baseline kidney function (e.g., eGFR) alters by > 20% or when there is a change in the clinical status of the patient.

For further information refer the eviQ Factsheet around carboplatin dosing and the carboplatin drug monograph within the ADDIKD guideline. To assist with calculations, use the eviQ Estimated Glomerular Filtration Rate (eGFR) and carboplatin dose calculators.

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 and fluorouracil by 25% for subsequent cycles
Febrile neutropenia Delay treatment until recovery and consider reducing carboplatin and fluorouracil by 25% for subsequent cycles
Platelets x 109/L (pre-treatment blood test) 
75 to less than 100 The general recommendation is to delay, however if the patient is clinically well it may be appropriate to continue treatment; refer to treating team and/or local institutional guidelines.
50 to less than 75 Delay treatment until recovery
less than 50 Delay treatment until recovery and consider reducing carboplatin and fluorouracil by 25% for subsequent cycles
Renal impairment
Creatinine clearance (mL/min)
30 to 50 Reduce fluorouracil by 25% and recalculate carboplatin dose using Calvert formula
less than 30 Reduce fluorouracil by 50% and recalculate carboplatin dose using Calvert formula based on measured glomerular filtration rate (GFR) or consider omitting
Hepatic impairment
Hepatic dysfunction
Mild No dose modifications necessary
Moderate Reduce fluorouracil by 25%
Severe Reduce fluorouracil by 50%
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:
1st occurrence: No dose reduction
2nd occurrence: Reduce fluorouracil by 25%
3rd occurrence: Reduce fluorouracil by 50%
4th occurrence: Omit fluorouracil
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:
1st occurrence: Reduce fluorouracil by 50%
2nd occurrence: Omit fluorouracil
Diarrhoea
Grade 2 Delay treatment until toxicity has resolved to Grade 1 or less and reduce the dose for subsequent cycles as follows:
1st occurrence: No dose reduction
2nd occurrence: Reduce fluorouracil 25%
3rd occurrence: Reduce fluorouracil by 50%
4th occurrence: Omit fluorouracil
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:
1st occurrence: Reduce fluorouracil by 50%
2nd occurrence: Omit fluorouracil
Hand foot syndrome (link to Hand foot syndrome (Palmar-plantar erythrodysaesthesia))
Grade 2 Delay treatment until toxicity has resolved to Grade 1 or less and reduce the dose for subsequent cycles as follows:
1st occurrence: No dose reduction
2nd occurrence: Reduce fluorouracil 25%
3rd occurrence: Reduce fluorouracil by 50%
4th occurrence: Omit fluorouracil
Grade 3 Delay treatment until toxicity has resolved to Grade 1 or less and reduce the dose for subsequent cycles as follows:
1st occurrence: Reduce fluorouracil by 50%
2nd occurrence: Omit fluorouracil

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

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

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
Fluorouracil
  Interaction Clinical management
Folic acid Increased toxicity of fluorouracil due to stabilisation of its bond to thymidylate synthetase (folic acid is a precursor of folinic acid/leucovorin) Advise patients not to take folic acid supplements (inc. multivitamins) around the time of receiving treatment with fluorouracil
Metronidazole, tinidazole Increased toxicity of fluorouracil due to reduced clearance Avoid combination or monitor for fluorouracil toxicity
Warfarin and other drugs metabolised by CYP2C9 (e.g. warfarin, phenytoin etc.) Increased effect/toxicity of these drugs due to inhibition of CYP2C9 by fluorouracil resulting in reduced clearance Avoid combination or monitor for increased effect/toxicity of these drugs (e.g. for bleeding/elevated INR with warfarin, elevated phenytoin serum levels or signs of toxicity such as ataxia, tremor etc.)
Allopurinol Reduced efficacy of fluorouracil possible due to reduced conversion to the active metabolites Avoid combination or monitor for reduced fluorouracil efficacy
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 website for further information.

Day 1

Approximate treatment time: 90 minutes

General patient assessment prior to each treatment.

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

Prime IV line(s).

Access TIVAD or CVAD.

Pre treatment medication

Verify antiemetics taken or administer as prescribed.

Verify dexamethasone taken or administer as prescribed.

Carboplatin 

Administer carboplatin (irritant):
  • via IV infusion over 30 to 60 minutes
  • observe for hypersensitivity reactions
  • flush with ~100 mL of sodium chloride 0.9%
  • hypersensitivity risk increases with number of cycles administered.
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.

Fluorouracil continuous infusion (irritant)

Connect pump containing fluorouracil and administer over the correct time for the amount of drug in the pump:

  • safety alert issued for administration of infusional fluorouracil
  • verify the correct rate of infusion via the ambulatory infusion pump
  • read more information about the different ambulatory infusion pumps.

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

Day 5

Approximate treatment time: 30 minutes

Safe handling and waste management

Disconnection of ambulatory infusion pump/infusor

Verify the ambulatory infusion pump/infusor is complete.

Disconnect the ambulatory infusion pump/infusor as per recommended procedure for type of pump/infusor.

Read more about ambulatory infusion pumps/infusors.

Deaccess TIVAD or CVAD.

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

Discharge Information

Antiemetics
  • Antiemetics as prescribed.
Antidiarrhoeals
  • Antidiarrhoeals as prescribed.
Patient information
  • Ensure patient receives patient information sheet.
Infusion pumps

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 
Cardiotoxicity

Coronary artery spasm is a temporary, sudden narrowing of one of the coronary arteries that may present at any time during treatment with fluoropyrimidines. It most commonly manifests as angina.
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
Oral mucositis

Erythematous and ulcerative lesions of the gastrointestinal tract (GIT). It commonly develops following chemotherapy, 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
Diarrhoea

Read more about treatment induced diarrhoea
Fatigue

Read more about fatigue
Anorexia

Loss of appetite accompanied by decreased food intake.

Read more about anorexia
Ocular changes

Symptoms may include eye pain, blurred vision, blepharitis, uveitis, optic neuritis, tear duct stenosis, conjunctivitis, hyperlacrimation, watery or dry eyes and photophobia. 
Actinic keratoses flare

Pre-existing actinic keratoses (AKs) can become more inflamed and scaly as a result of immunosuppression. 

Read more about actinic keratoses flare
Photosensitivity

Increased sensitivity to ultraviolet (UV) light resulting in an exaggerated sunburn-like reaction accompanied by stinging sensations and urticaria.
Palmar-plantar erythrodysaesthesia (PPE) - hand-foot syndrome (HFS)

Bilateral erythema, tenderness, pain, swelling, tingling, numbness, pruritus, dry rash, or moist desquamation and ulceration of the palms and soles. It is also known as hand-foot syndrome (HFS). Symptoms appear to be dose dependent and palms are affected more than soles.

Read more about hand-foot syndrome associated with chemotherapy

Late (onset weeks to months)
Anaemia

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

Read more about anaemia
Hyperpigmentation

Darkening of an area of skin caused by the overproduction of melanin.
Nail changes

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

Read more about nail toxicities
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

A search of the literature only finds one study to support the use of carboplatin 5FU in metastatic H&N SCC. This study randomised 277 patients to one of 3 treatment arms. 1. Cisplatin 100 mg/m² IV day 1 + fluorouracil 1000 mg/m² per day as a continuous IV infusion for 96 hours every 3 weeks, 2. Carboplatin 300 mg/m² IV day 1 + fluorouracil 1000 mg/m² per day as a continuous IV infusion for 96 hours every 3 weeks, 3. Methotrexate 40 mg/m² IV weekly.r A search of the literature did not find strong evidence to support the use of carboplatin and fluorouracil in the treatment of recurrent or metastatic squamous cell head and neck 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 study by Forastiere.r

Source Study and year published Supports use Is the dose and regimen consistent with the protocol Comments
Phase III trials Forastiere et al 1992 r Yes No Carboplatin 300mg/m2 d1 Fluorouracil 1000mg/m2 d1 CI over 96 hours q28d
Guidelines Date published/revised Supports use Is the dose and regimen consistent with the protocol Comments
NCCN 2016 Yes No doses stated -
BCCA 2016 Yes No Carboplatin 70mg/m2 d1-4 Fluorouracil 2400mg/m2/day CI d1-4
CCO 2013 Yes Yes -

Efficacy

Forastiere et al concluded from their randomised study that combination chemotherapy resulted in improved response rates but was associated with increased toxicity and no improvement in overall survival. Therefore new treatments that may alter the course of disease in recurrent head and neck cancer patients still need to be identified.r

Forastierer​  Cisplatin/5FU
(%)		 Carboplatin/5FU
(%)		 Methotrexate
(%)
Complete response 6 2 2
Partial response 26 19 8
Stable/no response 37 42 50
Increasing disease 16 25 32
Assumed no response* 15 12 8

* early death or not assessable

Toxicity 

Toxicityr Cisplatin/5FU  Carboplatin/5FU  Methotrexate 
Grade 1 to 2
(%)		 Grade 3 to 4
(%)		 Grade 1 to 2
(%)		 Grade 3 to 4
(%)		 Grade 1 to 2
(%)		 Grade 3 to 4
(%) 
Anaemia 55 5 42 14 25 3
Leukopenia 42 31 50 12 29 16
Thrombocytopenia 13 6 19 13 9 6
Diarrhoea 12 2 6 2 3 0
Stomatitis 19 14 28 15 34 10 
Nausea/vomiting 68 8 48 6 38 8
Peripheral neuropathy 5 1 2 0 0 0
Ototoxicity 8 4 2 0 2 0
Renal 18 9 1 1 3 3
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Version 5

Date Summary of changes
27/07/2007 New clinical instructions for health professionals and patients.
16/10/2007 Safety alert added.
26/03/2010 Review, new dose modifications and transferred to eviQ.
02/07/2010 Haematological dose modifications updated (20% changed to 25% dose reduction).
07/06/2011 PHC view created.
29/07/2011 Protocol reviewed at reference committee meeting 29/07/11.
Title updated to include use in the recurrent setting.
17/08/2011 New format to allow for export of protocol information.
Protocol version number changed to V.2.
Antiemetics and premedications added to the treatment schedule.
Additional Clinical Information, Key Prescribing table and Key Administration table combined into new section titled Clinical Information.
Drug specific information placed behind the drug name link.
Infusion fluid for carboplatin changed from sodium chloride 0.9% to glucose 5% because of longer stability.
FAQ: Question on alcohol removed.
10/11/2011 Drug cost recalculated to $410 (was previously $752).
Link to the new protocol ID 1204 carboplatin fluorouracil with cetuximab added.
Dental assessment information removed as more relevant to protocols with radiotherapy.
Patient information - added information on pump change.
10/04/2012 PHC OMIS view updated.
01/05/2012 Palonosetron added as the preferred 5HT3 antagonist for moderate emetogenicity.
03/05/2013 Protocol Reviewed at Medical Oncology Reference Committee meeting.
Next review in 2 years.
20/08/2014 PHC view removed.
09/03/2015 Carboplatin dosing - for estimated GFR > 125 mL/min, note about measuring GFR and/or dose capping added.
19/06/2015 Reviewed electronically by Medical Oncology Reference Committee. No changes. Review 2 years.
16/10/2016 Patient information sheet updated to include more fluorouracil toxicity symptom warnings.
28/10/2016 Protocol reviewed by Medical Oncology Reference Committee. Evidence transferred to limited evidence template.
31/05/2017

Transferred to new eviQ website. Version number changed to V.3.

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.
16/03/2018 Hepatic dose modifications updated to be consistent with other head and neck recurrent protocols.
10/05/2018

Haematological dose modifications updated as per consensus of the expert clinician group. Fluoropyrimidine overdose warning added. DPD enzyme deficiency wording in clinical information updated. Fluoropyrimidine safety alert wording in clinical information updated. Version changed to number V.4.
13/02/2019 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
15/03/2019 Protocol reviewed by Medical Oncology Reference Committee. No changes. Review 5 years.

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https://www.eviq.org.au/p/280

30 Sep 2023