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Nasopharyngeal locally advanced adjuvant ciSplatin and fluorouracil (following chemoradiation)

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.

 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.

Dihydropyrimidine dehydrogenase (DPD) enzyme deficiency:

Testing for DPD enzyme deficiency is available in Australia but not currently reimbursed. Read more about dihydropyrimidine dehydrogenase (DPD) enzyme deficiency

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.

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

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Cycle 1 to 3

Drug Dose Route Day
ciSplatin 80 mg/m2 IV infusion 1
Fluorouracil 4,000 mg/m2 (equivalent to 1000 mg/m2/day) CIV over 96 hours 1
Frequency:
28 days 
Cycles:
3 (this protocol follows chemoradiation after a 3 to 4 week break)
Notes:

While adjuvant chemotherapy has been the standard part of many concurrent chemoradiation therapy regimens, its benefit is uncertain and toxicity is substantial. It should only be considered in patients with high risk (T3 & T4) disease, good performance status and adequate recovery from the toxicity of chemoradiation therapy. See evidence section.

Drug status:

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

Cost:
~ $230 "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 to 3

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 12 mg (PO) 60 minutes before chemotherapy
ciSplatin 80 mg/m2 (IV infusion) in 1000 mL sodium chloride 0.9% over 60 minutes
Fluorouracil 4,000 mg/m2 (CIV) via ambulatory infusion pump over 96 hours (equivalent to 1000 mg/m2/day)
Day 2 to 4
Dexamethasone 8 mg (PO) ONCE a day (or in divided doses) with or after food.
Frequency:
28 days 
Cycles:
3 (this protocol follows chemoradiation after a 3 to 4 week break)

Cycle 1 to 3

Drug Dose Route Day
ciSplatin 80 mg/m2 IV infusion 1
Fluorouracil 4,000 mg/m2 (equivalent to 1000 mg/m2/day) CIV over 96 hours 1
Frequency:
28 days 
Cycles:
3 (this protocol follows chemoradiation after a 3 to 4 week break)
Notes:

While adjuvant chemotherapy has been the standard part of many concurrent chemoradiation therapy regimens, its benefit is uncertain and toxicity is substantial. It should only be considered in patients with high risk (T3 & T4) disease, good performance status and adequate recovery from the toxicity of chemoradiation therapy. See evidence section.

Drug status:

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

Cost:
~ $230 "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 to 3

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 12 mg (PO) 60 minutes before chemotherapy
ciSplatin 80 mg/m2 (IV infusion) in 1000 mL sodium chloride 0.9% over 60 minutes
Fluorouracil 4,000 mg/m2 (CIV) via ambulatory infusion pump over 96 hours (equivalent to 1000 mg/m2/day)
Day 2 to 4
Dexamethasone 8 mg (PO) ONCE a day (or in divided doses) with or after food.
Frequency:
28 days 
Cycles:
3 (this protocol follows chemoradiation after a 3 to 4 week break)

Indications:

  • Adjuvant chemotherapy 3 to 4 weeks following chemoradiation and after adequate recovery from acute radiation toxicities in patients with locally advanced stage III or IV nasopharyngeal cancer
    • this regimen should only be considered in patients with good performance status

Cautions/Exclusions:

  • pre existing neuropathies Grade 2 or greater
  • significant hearing impairment/tinnitus.
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 opens in a new tab or window 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
Emetogenicity HIGH

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

Ensure that patients also have sufficient antiemetics for breakthrough emesis:

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

Prochlorperazine 10 mg PO every 6 hours when necessary.

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

Dental assessment is recommended for all patients prior to starting treatment

Read more about health professional dental considerations for patients starting head and neck treatment
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
Cisplatin dosing

Directly measured glomerular filtration rate (mGFR) is preferred for initial dosing when eGFR < 60 mL/min/1.73 m2, especially when cisplatin dose > 50 mg/m2 or when eGFR is unreliable (e.g., extremes of body composition, amputees, paraplegia).

Read more about prevention and management of cisplatin induced nephrotoxicity.
Hydration

Hydration helps to prevent cisplatin-induced nephrotoxicity.

The default regimen is appropriate for patients with normal electrolytes, kidney function, fluid status etc. and should be adjusted according to individual requirements.

Read more about cisplatin hydration regimens
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 opens in a new tab or window 
Ototoxicity

Ototoxicity may occur with platinum-based therapy; patients should be monitored for signs and symptoms. Platinum compounds should be used with caution in patients with pre-existing conditions or risk factors.

Ototoxicity may become more severe in patients being treated with other drugs with nephrotoxic potential e.g. aminoglycosides.

An audiometry test should be performed if symptoms develop.

Read more about ototoxicity - tinnitus and hearing loss
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
Speech pathology

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

FBC, EUC, eGFR, LFTs, calcium and magnesium at baseline and prior to each cycle.
Hepatitis B screening and prophylaxis

Routine screening for HBsAg and anti-HBc is recommended prior to initiation of treatment. Prophylaxis should be determined according to individual institutional policy. 

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

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

For more information about vaccinations in people with cancer refer to the Australian Immunisation Handbook opens in a new tab or window.
Fertility, 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
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)
0.5 to less than 1.0 Delay treatment until recovery
less than 0.5 Delay treatment until recovery and consider reducing cisplatin and fluorouracil by 25% for subsequent cycles
Febrile neutropenia Delay treatment until recovery and consider reducing cisplatin and fluorouracil by 25% for subsequent cycles
Platelets x 109/L (pre-treatment blood test)
75 to less than 100 Refer to local institutional guidelines; it is the view of the expert clinicians that treatment should continue if patient is clinically well
50 to less than 75 Delay treatment until recovery
less than 50 Delay treatment until recovery and consider reducing cisplatin and fluorouracil by 25% for subsequent cycles
Kidney dosing recommendations 
  • Suggested dose modifications are based on the International Consensus Guideline on Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD).
  • Where one or more drugs in a protocol is recommended to be avoided, consider using a clinically appropriate alternative treatment protocol instead.
  • Before dose adjusting or omitting a drug, consider treatment intent.
  • In kidney replacement therapy consult a multidisciplinary team consisting of oncology/haematology with nephrology and/or clinical pharmacology for the management of dosing. 
  • For complete information on individual drug recommendations please review the individual drug monograph in the ADDIKD guideline.
eGFR
(mL/min/1.73m2)		 Cisplatin Fluorouracil
≥ 60

Full dose

Full dose
45 - 59

Alternative protocol

OR

Reduce by 25 to 50%*

Potential for increased risk of adverse events

Full dose

Increased risk of adverse events
30 - 44

AVOID

Cisplatin not recommended.

Consider substituting carboplatin for cisplatin**

Full dose

Increased risk of adverse events
15 - 29

AVOID

Not recommended - use alternative protocol

Alternative protocol

This drug may be given at this eGFR level (see ADDIKD guideline) however not recommended in this protocol
< 15
(without kidney replacement therapy)

AVOID

Not recommended - use alternative protocol

AVOID

Not recommended - use alternative protocol

* Extent of dose reduction should take into account intent of treatment, performance status, potential total cumulative cisplatin exposure.

** This differs from the ADDIKD Guideline and is based on RCM consensus 2024.
Hepatic impairment
Hepatic dysfunction
Mild No dose modifications necessary
Moderate Reduce fluorouracil by 25%
Severe Reduce fluorouracil by 50%
Peripheral neuropathy
Grade 2, Grade 3 or Grade 4 Omit cisplatin and consider substituting carboplatin for cisplatin
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%
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%
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%
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

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.

Cisplatin
  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
Neurotoxic drugs (e.g. vincristine, paclitaxel) Additive neurotoxicity Monitor closely for neuropathy if combination used
Paclitaxel Administration schedule may influence the development of myelosuppression Minimise toxicity by administering paclitaxel first in regimens using the combination
Carbamazepine, phenytoin, valproate Decreased antiepileptic plasma levels Monitor antiepileptic serum levels and seizure frequency for efficacy; adjust dosage as appropriate or select alternative antiepileptic (e.g. clonazepam, diazepam, lorazepam)
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 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: 4.5 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.

Mucositis is common with this protocol. Discussion with treating clinicians, including radiation oncologists, before modification is recommended. 

Oral mucositis/stomatitis assessment tool prior to each treatment.

Prior to administration

Prime IV line(s).

Access TIVAD or CVAD.

Pre treatment medication

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

Cisplatin

Commence prehydration for cisplatin:
  • administer 10 mmol magnesium sulphate (MgSO4) in 1000 mL sodium chloride 0.9% over 60 minutes
  • ensure patient has passed urine prior to cisplatin administration as per institutional policy.
Administer cisplatin (irritant):
  • via IV infusion over 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 when given with concomitant radiation therapy. 
Infusion-related reaction (IRR):

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

Post hydration:
  • 1000 mL sodium chloride 0.9% over 60 minutes.

Fluorouracil continuous infusion (irritant)

Safety alert fluoropyrimidines

Administer fluorouracil:

Post administration

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.

Post administration

Deaccess TIVAD or CVAD.

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

Discharge Information

Discharge medications

Antiemetics - as/if prescribed.

Antidiarrhoeals - as/if prescribed.

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)
Nausea and vomiting

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

Read more about taste and smell changes
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.

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 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
Anorexia

Loss of appetite accompanied by decreased food intake.

Read more about anorexia
Fatigue

Read more about fatigue
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.
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
Nephrotoxicity

Kidney dysfunction resulting from damage to the glomeruli, tubules or renal vasculature.
Hypomagnesaemia, hypokalaemia, hypocalcaemia

Abnormally low levels of magnesium, potassium and calcium in the blood.
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
Ototoxicity

Tinnitus and hearing loss may occur due to damage in the inner ear. Tinnitus is usually reversible, while hearing loss is generally irreversible. Hearing loss is dose-related, cumulative and may be worse in those with pre-existing hearing problems.

Read more about ototoxicity - tinnitus and hearing loss

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, subungual haematoma and subungual 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

Meta-analyses have confirmed an improvement in overall survival with the addition of concomitant chemotherapy to radiation therapy. The value of adjuvant chemotherapy in addition to concomitant chemoradiation therapy is uncertain.rr

A study was undertaken by Lee at el.r to verify the long-term therapeutic index of the Intergroup-0099 Study. Between March 1999 and January 2004, a total of 348 patients were randomised. The primary endpoints included failure-free rate (FFR) and progression-free survival. Secondary endpoints included overall survival, locoregional FFR, distant FFR, and acute and late toxicity rates. Adding concurrent-adjuvant chemotherapy statistically significantly reduced failure and cancer-specific deaths when compared with radiation therapy alone and although there was no statistically significant increase in major late toxicity, increase in noncancer deaths narrowed the resultant gain in overall survival.r

The meta-analyses conducted by Baujat et al. and Langendijk suggested no significant benefit.rr More recently Ouyang et al suggest a benefit of locoregional control but not in OS.r

Efficacy

Al-Sarraf et al.r registered 193 patients, 147 (69 radiation therapy and 78 chemoradiation therapy) were eligible for primary analysis for survival and toxicity. The median PFS time was 15 months for eligible patients on the radiation therapy arm and was not reached for the chemoradiation therapy group. The 3-year PFS rate was 24% versus 69%, respectively (p<0.001). The median survival time was 34 months for the radiation therapy group and not reached for the chemoradiation therapy group, and the 3-year survival rate was 47% versus 78%, respectively (p=0.005). 185 patients were included in a secondary analysis for survival. The 3-year survival rate for patients randomised to radiation therapy was 46%, and for the chemoradiation therapy group was 76% (p<0.001).r

Wee et alr randomised 110 patients to RT and 111 to CRT with 2 and 3 year overall survival rates of 78% and 85% and 65% and 80% for RT alone and CRT, respectively with a hazard ratio of 0.51 (CI 0.31 to 0.81, p=0.0061). Distant metastases were seen in 38 patients receiving RT alone versus 18 who received CRT.r

Overall survival by treatmentr

© Journal of Clinical Oncology 2005

Toxicity

Toxicityr
(Grades 3 and 4)

Radiation therapy only
(initial phase)
n=107
(%)

 Chemoradiation therapy
(initial phase)
n=106
(%)

Chemoradiation therapy
(adjuvant phase)
n=73
(%)
Mucositis/pharyngitis 32 48 5
Anorexia 4 22 4
Emesis 0 5 1
Skin 5 5 0
Other* 0 4 3
Neutrophils 0 13 33
Platelets 0 2 0
Other** 0 0 4

*Initial phase: renal toxicity, infection and metabolic toxicity. Adjuvant phase: GI toxicity and infection
** Included 1 haemoglobin and 2 WBC toxicities

© Journal of Clinical Oncology 2005

[%id%]
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Version 6

Date Summary of changes
04/04/2024 ​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.6.

Version 5

Date Summary of changes
31/01/2024 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.5. Read more about as required review protocol status in this factsheet.

 

Version 4

Date Summary of changes
27/07/2007 New clinical instructions and patient sheet updated.
16/10/2007 Safety alert added.
26/03/2010 Review, new dose modifications and transferred to eviQ.
13/05/2010 Cisplatin hydration changed to outpatient regimen.
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
Protocol split into 2 protocols:
  • ID 277 Nasopharyngeal locally advanced chemoradiation cisplatin (three weekly) and
  • ID 1154 Nasopharyngeal locally advanced adjuvant cisplatin and fluorouracil (following chemoradiation)
SCC removed from the title as this protocol can be used in both squamous cell carcinoma (SCC) and undifferentiated carcinoma.
Treatment schedule (ID 1154) - Frequency updated to every 28 days only (was 21 or 28 days), adjuvant chemotherapy to be commenced 3 to 4 weeks following chemoradiation and after adequate recovery of acute radiation toxicities.
Dose modifications for renal impairment - cisplatin omitted in patients with creatinine clearance less than 50 mL/min.
Dose modifications for peripheral neuropathy - cisplatin omitted in patients grade 2 or above peripheral neuropathy.
Dose modifications for mucositis removed as it is more likely to be related to radiotherapy component of the treatment.
Dose modifications for 3rd and 4th occurrences removed as only 3 cycles.
22/08/2011 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.
FAQ: Question on alcohol removed.
10/04/2012 PHC OMIS view updated.
03/05/2013 Reviewed at Medical Oncology Reference Committee meeting. Evidence updated. Review in 2 years.
01/06/2012 PHC CVAD Pre Clin added. PHC OMIS view published.
10/07/2013 Dose modifications for cisplatin updated.
12/08/2014 PHC view removed.
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.
31/05/2017

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

Antiemetic change: Netupitant/palonosetron combination has replaced aprepitant and a 5HT3 receptor antagonist in combination with dexamethasone for all highly emetogenic regimens.
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.
15/03/2019 Protocol reviewed by Medical Oncology Reference Committee. No changes. Review 5 years.
31/03/2023 Protocol reviewed by Medical Oncology Reference Committee. No changes. Next review in 2 years.

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04 May 2025