1. Home
  2. Medical oncology
  3. Colorectal
  4. Anal

Anal definitive ciSplatin and fluorouracil 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.

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

On this page
Expand all Collapse all Back to top
Drug Dose Route Day
ciSplatin 60 mg/m2 IV infusion 1 and 29
Fluorouracil 4,000 mg/m2 (equivalent to 1000 mg/m2/day) CIV via pump over 96 hours 1 and 29
Cycles:
1 with concurrent radiation therapy
Notes:

Both radiation oncologists and medical oncologists need to be involved in decisions regarding treatment delays or dose alterations.

Concurrent chemoradiation with mitomycin/5-FU remains the standard of care for anal cancer, however, the use of cisplatin/5-FU is also a reasonable alternate approach in some patients in whom the toxicity of mitomycin would be considered unacceptable or where mitomycin is contraindicated such as idiosyncratic or hypersensitivity reactions, coagulation and bleeding disorders and thrombocytopenia (platelets less than 100 x 109/L).

As the majority of clinical trials have excluded patients with HIV/AIDS, information is limited on how to treat such patients. Prior to the HAART (highly active antiretroviral therapy) era, patients with HIV/AIDS were reported to have reduced survival and significant acute toxicities to standard chemoradiation therapy. Since the introduction of HAART, there has been evidence to suggest that chemoradiation therapy with mitomycin/5-FU may be safe and effective in this patient populationrr. However, other factors such as performance status, CD4 count, compliance with HAART, HIV/AIDS-related complications (e.g. opportunistic infections etc.) need to be taken into consideration when determining a treatment regimen and/or dose adjustments.

Drug status:

All drugs in this protocol are on the PBS general schedule

Cost:
~ $420 per cycle "How this cost is calculated"

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

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

Drug unit costs are taken directly from the Pharmaceutical Benefits Scheme (PBS) website (www.pbs.gov.au). These costs are reviewed and updated on eviQ at 6 monthly intervals. Anti-cancer drugs that are not included on the PBS do not have a cost included in eviQ protocols.

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

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

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

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

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

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

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

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 60 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.
Day 29
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 60 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 30 to 32
Dexamethasone 8 mg (PO) ONCE a day (or in divided doses) with or after food.
Cycles:
1 with concurrent radiation therapy
Drug Dose Route Day
ciSplatin 60 mg/m2 IV infusion 1 and 29
Fluorouracil 4,000 mg/m2 (equivalent to 1000 mg/m2/day) CIV via pump over 96 hours 1 and 29
Cycles:
1 with concurrent radiation therapy
Notes:

Both radiation oncologists and medical oncologists need to be involved in decisions regarding treatment delays or dose alterations.

Concurrent chemoradiation with mitomycin/5-FU remains the standard of care for anal cancer, however, the use of cisplatin/5-FU is also a reasonable alternate approach in some patients in whom the toxicity of mitomycin would be considered unacceptable or where mitomycin is contraindicated such as idiosyncratic or hypersensitivity reactions, coagulation and bleeding disorders and thrombocytopenia (platelets less than 100 x 109/L).

As the majority of clinical trials have excluded patients with HIV/AIDS, information is limited on how to treat such patients. Prior to the HAART (highly active antiretroviral therapy) era, patients with HIV/AIDS were reported to have reduced survival and significant acute toxicities to standard chemoradiation therapy. Since the introduction of HAART, there has been evidence to suggest that chemoradiation therapy with mitomycin/5-FU may be safe and effective in this patient populationrr. However, other factors such as performance status, CD4 count, compliance with HAART, HIV/AIDS-related complications (e.g. opportunistic infections etc.) need to be taken into consideration when determining a treatment regimen and/or dose adjustments.

Drug status:

All drugs in this protocol are on the PBS general schedule

Cost:
~ $420 per cycle "How this cost is calculated"

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

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

Drug unit costs are taken directly from the Pharmaceutical Benefits Scheme (PBS) website (www.pbs.gov.au). These costs are reviewed and updated on eviQ at 6 monthly intervals. Anti-cancer drugs that are not included on the PBS do not have a cost included in eviQ protocols.

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

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

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

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

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

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

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

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 60 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.
Day 29
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 60 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 30 to 32
Dexamethasone 8 mg (PO) ONCE a day (or in divided doses) with or after food.
Cycles:
1 with concurrent radiation therapy

Indications:

  • primary treatment of anal cancer in patients in whom the toxicity of mitomycin would be considered unacceptable or in rare situations where mitomycin is contraindicated.

Cautions / exclusions:

  • pre existing neuropathies greater than or equal to Grade 2 
  • 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 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
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
Diarrhoea

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

Read more about treatment induced diarrhoea
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
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
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
Blood tests

FBC, EUC, eGFR, LFTs, calcium and magnesium at baseline and prior to each treatment.
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.

Refer to the recommended schedule of vaccination for immunocompromised patients, as outlined in the Australian Immunisation Handbook.

Read more about COVID-19 vaccines and cancer.
Fertility, pregnancy and lactation

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

Read more about the impact of cancer treatment on fertility
Evidence for dose modifications is limited, and the recommendations made on eviQ are intended as a guide only. They are generally conservative with an emphasis on safety. Any dose modification should be based on clinical judgement, and the individual patient’s situation including but not limited to treatment intent (curative vs palliative), the anti-cancer regimen (single versus combination therapy versus chemotherapy versus immunotherapy), biology of the cancer (site, size, mutations, metastases), other treatment related side effects, additional co-morbidities, performance status and patient preferences.Suggested dose modifications are based on clinical trial findings, product information, published guidelines and reference committee consensus . The dose reduction applies to each individual dose and not to the total number of days or duration of treatment cycle unless stated otherwise. Non-haematological gradings are based on Common Terminology Criteria for Adverse Events (CTCAE) unless otherwise specified. Renal and hepatic dose modifications have been standardised where possible. For more information see dosing considerations & disclaimer.

Note: All dose reductions are calculated as a percentage of the starting dose.

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

Consider a 25% reduction

Potential for increased risk of adverse events

Full dose

Increased risk of adverse events
30 - 44

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 - 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
Hepatic impairment
Hepatic dysfunction
Mild No dose modifications necessary
Moderate Reduce fluorouracil by 25%
Severe Reduce fluorouracil by 50%
Peripheral neuropathy
Grade 2 which is present at the start of the next cycle Reduce cisplatin by 25% or consider alternative therapy
Grade 3 or Grade 4 Omit cisplatin and consider alternative therapy
Mucositis and stomatitis
Grade 2 Delay treatment until toxicity has resolved to Grade 1 or less
Grade 3 or Grade 4 Delay treatment until toxicity has resolved to Grade 1 or less and reduce fluorouracil by 50% for subsequent cycles
Diarrhoea
Grade 2 Delay treatment until toxicity has resolved to Grade 1 or less
Grade 3 or Grade 4 Delay treatment until toxicity has resolved to Grade 1 or less and reduce fluorouracil by 50% for subsequent cycles
Hand foot syndrome (link to Hand foot syndrome (Palmar-plantar erythrodysaesthesia)
Grade 2 Delay treatment until toxicity has resolved to Grade 1 or less
Grade 3 Delay treatment until toxicity has resolved to Grade 1 or less and reduce fluorouracil by 50% for subsequent cycles

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 and P‑gp inhibitors. If treating VTE, avoid use with strong CYP3A4 and P‑gp inducers. 

Rivaroxaban: avoid concurrent use with strong CYP3A4 and P‑gp  inhibitors.

Dabigatran: avoid combination with strong P‑gp inducers and inhibitors.

If concurrent use is unavoidable, monitor closely for efficacy/toxicity of both drugs.
Digoxin Anti-cancer drugs can damage the lining of the intestine; affecting the absorption of digoxin. Monitor digoxin serum levels; adjust digoxin dosage as appropriate.
Antiepileptics Both altered antiepileptic and anti-cancer drug levels may occur, possibly leading to loss of efficacy or toxicity. Where concurrent use of an enzyme-inducing antiepileptic cannot be avoided, monitor antiepileptic serum levels for toxicity, as well as seizure frequency for efficacy; adjust dosage as appropriate.
Also monitor closely for efficacy of the anti-cancer therapy.
Antiplatelet agents and NSAIDs Increased risk of bleeding due to treatment related thrombocytopenia. Avoid or minimise combination.
If combination deemed essential, (e.g. low dose aspirin for ischaemic heart disease) monitor for signs of bleeding.
Serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs e.g. paroxetine) and serotonin noradrenaline reuptake inhibitors (SNRIs e.g. venlafaxine) Increased risk of serotonin syndrome with concurrent use of 5-HT3 receptor antagonists (e.g. palonosetron, ondansetron, granisetron, tropisetron, dolasetron, etc.) Avoid combination.
If combination is clinically warranted, monitor for signs and symptoms of serotonin syndrome (e.g. confusion, agitation, tachycardia, hyperreflexia).
For more information link to TGA Medicines Safety Update
Vaccines Diminished response to vaccines and increased risk of infection with live vaccines. Live vaccines (e.g. BCG, MMR, zoster and varicella) are contraindicated in patients on immunosuppressive therapy. Use with caution in patients on non-immunosuppressive therapy.
For more information; refer to the recommended schedule of vaccination for cancer patients, as outlined in the Australian Immunisation Handbook

eviQ provides safe and effective instructions on how to administer cancer treatments. However, eviQ does not provide every treatment delivery option, and is unable to provide a comprehensive list of cancer treatment agents and their required IV line giving set/filter. There may be alternative methods of treatment administration, and alternative supportive treatments that are also appropriate. Please refer to the individual product information monographs via the TGA and Australian Injectable Drugs Handbook websites for further information.

Day 1 and 29

Approximate treatment time: 4 hours

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

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

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

Prime IV line(s).

Access TIVAD or CVAD.

Pre treatment medication

Verify antiemetics taken or administer as prescribed.

Verify dexamethasone taken or administer as prescribed.

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)

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 and 33

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 - 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)
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
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
Ocular changes

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

Read more about fatigue
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
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
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.
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

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

Mitomycin/5-FU with concurrent radiation therapy remains the standard of care for anal cancer, however, the use of cisplatin/5-FU is also a reasonable approach in some patients for instance those with HIV or in whom the toxicity of mitomycin would be considered unacceptable.

A large prospective randomised trial, RTOG 98-11,r compared mitomycin/5-FU in combination with radiation therapy, directly to cisplatin/5-FU in combination with radiation therapy. 682 patients with anal canal carcinoma were randomised to either mitomycin 10 mg/m2 day 1 and day 29 combined with infusional 5-FU 1000 mg/m2/day day 1 to 4 or cisplatin 75 mg/m2 day 1, day 29, day 57 and day 85 combined with infusional 5-FU 1000 mg/m2/day day 1 to 4, day 29 to 32, day 57 to 60 and day 85 to 88. Both regimens were given radiation therapy at a minimum dose of 45 Gy in 25 fractions. Patients with established AIDS were excluded.r

The primary endpoint was 5-year disease-free survival (DFS). Secondary end points were overall survival (OS) and time to relapse.

ACT II,r a large randomised multicentre trial investigated the role of replacing mitomycin with cisplatin in improving responses with acceptable toxicity and whether maintenance treatment after chemoradiation improves survival. Between June 2001, and December 2008, 940 patients with histologically proven anal squamous, basaloid or cloacogenic carcinoma were equally randomised in a 2x2 factorial design to receive 5-FU 1000 mg/m2/day days 1 to 4 and days 29 to 32 and either mitomycin 12 mg/m2 day 1 or cisplatin 60 mg/m2 day 1 and day 29. Radiation therapy of 50.4 Gy was delivered in 28 daily fractions over 5.5 weeks with a two-phase technique. 4 weeks after chemoradiation, patients were also randomised to receive maintenance therapy (2 cycles of cisplatin and 5-FU weeks 11 and 14) or no maintenance.

The primary endpoints for comparing mitomycin with cisplatin were complete response (26 weeks from start of chemoradiation) and grade 3 or 4 toxicities (4 weeks after chemoradiation); and for comparing maintenance with no maintenance was progression-free survival (PFS). Secondary endpoints were colostomy-free survival (CFS), recurrence rate, cause-specific survival and OS.

Efficacy

RTOG 98-11rr

At the time of initial analysis, the median follow-up for all patients was 2.51 years. Although the 5 year DFS and OS rates were similar between both arms, the cumulative colostomy rate was significantly higher in the cisplatin/5-FU arm (10% versus 19%; p=0.02).r

Long-term analysis performed on 649 eligible patients out of the 682 accrued patients demonstrated significantly enhanced 5 year DFS and OS rates in the mitomycin/5-FU group compared to the cisplatin/5-FU group. There was a trend towards statistical significance for 5 year locoregional failure (LRF), CFS, colostomy failure (CF) and distant metastasis (DM) rates for patients treated with mitomycin/5-FU versus cisplatin/5-FU.r

Gundersonr Mitomycin/5-FU  Cisplatin/5-FU p-value
5 year DFS (%, 95% CI)

 67.8 (62.3-72.6)

57.8 (52.1-63.0)

 0.006
5 year OS (%, 95% CI)

78.3 (73.2-82.5)

70.7 (65.2-75.4) 

 0.026
5 year LRF (%, 95% CI)

20 (15.6-24.4)

26.4 (21.5-31.3)

 0.087
5 year CFS (%, 95% CI)

71.9 (66.5-76.5)

65 (59.4-70.0)

 0.05
5 year CF (%, 95% CI)

11.9 (8.3-15.4)

17.3 (13.1-21.5)

 0.074
5 year DM (%, 95% CI)

13.1 (9.3-16.8)

18.1 (13.8-22.4)

 0.12

Disease-free survival (A) and overall survival (B)r

© J Clin Oncol 2012

ACT IIr

The median follow-up was 5.1 years. 77% mitomycin group (365/472) and 72% cisplatin group (338/468) completed chemoradiation without delays or dose reductions. 46% mitomycin group (105/226) and 41% cisplatin group (91/222) completed both courses of maintenance treatment without delays or dose reductions. There were no significant differences in the complete responses (absolute difference -0.9%, 95% CI -4.9 to 3.1; p=0.64) between the mitomycin and the cisplatin arms. PFS did not differ significantly between patients who took mitomycin and cisplatin during chemoradiation (HR 0.95, 95% CI 0.75–1.19; p=0.63). The addition of maintenance treatment did not improve the 3 year PFS. The 3 year PFS was better in patients with T1-T2 and node negative patients in comparison with T3-T4 and node positive patients. There was no significant difference in the 3 year OS between mitomycin and cisplatin arms and the maintenance and no maintenance arms.

Primary tumour response at 26 weeksr Mitomycin group
(n=432)		 Cisplatin group
(n=431)
Complete response 391 (90.5%) 386 (89.6%)
Partial response 14 (3.2%) 24 (5.6%)
Stable disease 5 (1.2%) 6 (1.4%)
Progressive disease 22 (5.1%) 15 (3.5%)
Efficacyr Mitomycin
maintenance		 Cisplatin
maintenance		 Mitomycin,
no maintenance		 Cisplatin,
no maintenance
3 year PFS (%, 95% CI) 73 (66-78)  74 (68-80)  73 (67-78) 72 (66-78) 
3 year CFS (%, 95% CI) 73 (67-79) 75 (68-80) 75 (68-80) 72 (66-77)
3 year OS (%) 82 83  86 84

Progression free survival (A) maintenance versus non maintenance (B) all four groupsr

© Lancet Oncol 2013

Anal cancer mortality (A) cisplatin versus mitomycin (B) all four groupsr

© Lancet Oncol 2013

© Lancet Oncol 2013

Toxicity

RTOG 98-11r

The rate of grade 3 or 4 overall late treatment-related toxicities was not statistically different between the mitomycin- and cisplatin-based groups (13.1% versus 10.7%; p=0.35). Haematologic grade 3 or 4 toxicities showed a significantly greater incidence in the mitomycin-based group (61.8%) compared to the cisplatin-based group (42.0%) (p < 0.001).r

Treatment-related adverse eventsr

© J Clin Oncol 2012

ACT IIr

Patients in the mitomycin arm had more acute grade 3/4 haematological toxicities (26% versus 16%; p< 0.001) but no higher rates of febrile neutropenia (3.1% versus 3.2%; p=0.93). Non-haematologic grade 3/4 toxicities were similar between arms (61% versus 65%; p=0.22).

Treatment-related adverse eventsr

© Lancet Oncol 2013

[%id%]
[%title%]
[%abstract%]

Flinders Filters has partnered with eviQ to build reliable, robust search filters to retrieve core high level evidence on topics of significance to eviQ. The project goal is the provision of a sustainable model for evidence retrieval to ensure ongoing currency of content.

These search filters have been developed to retrieve the most up to date evidence from PubMed, in real time, using specifically designed search filters built to meet our needs.

Searches can be used when a protocol is scheduled for review or at any time you choose. Please click on the Specific, Balanced and Sensitive tabs below to access the Pubmed searches.

Specific Balanced Sensitive
restricted to retrieving randomised control trials and systematic reviews.

is the middle ground between sensitive and specific searches.

retrieves all clinically relevant evidence - generally a broader search on a given topic.

Access Flinders Filters, a division of the Flinders Digital Health Research Centre at Flinders University to read more about research solutions to searching problems.

Troubleshooting

Occasionally the searches may not display correctly or take too long to load (and will eventually timeout). This may be caused by Internet Explorer being unable to handle long URL's. You can rectify this by using Firefox, Safari or Google chrome. It is always a good idea to clear the cache regularly to ensure you are getting the most up to date search.

Feedback

If you identify any new articles that you believe should be included in the content, please use the feedback button below to inform us of the name of the article(s). 

Version 7

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.7. Read more about as required review protocol status in this factsheet.

Version 6

Date Summary of changes
14/09/2023

Protocol updated with ADDIKD guideline recommendations. New kidney dosing recommendation table added to dose modification section.

PDF of previous protocol.

Version number changed to V.6.

Version 5

Date Summary of changes
20/01/2022 Protocol reviewed electronically by Medical Oncology Reference Committee. Evidence updated with RTOG 98-11 long-term results. Version changed to V.5. Next review 5 years.

Version 4

Date Summary of changes
04/05/2007 Patient information updated
03/12/2007 Safety alert added
03/03/2010 New drug schedule as per ACT II trial. Previous treatment regimen CISCat ID 01-1199.1. Statement on treating patients with HIV included. Evidence updated, new dose modifications and transferred to eviQ.
28/06/2010 Haematological dose modifications updated ( 20% changed to 25% dose reduction)
26/03/2012

New format to allow for export of protocol information
Protocol version number changed to V.2
Title updated to include "definitive". "with radiotherapy changed to "chemoradiation"
Antiemetics and premedications added to the treatment schedule
Additional Clinical Information, Key Prescribing table and Key Administration table combined into new section titled Clinical Considerations
Drug specific information placed behind the drug name link
Treatment schedule changed from two cycles every 28 days to one cycle day 1 and 29
3/04/2012 PHC OMIS view updated
10/7/2013 Dose modifications for cisplatin updated
13/09/2013 Protocol reviewed at Medical Oncology Reference Committee
Evidence updated with James Lan Onc 2013
Next review in 2 years
08/09/2014 PHC view removed
18/09/2015 Link to radiation oncology protocol added
15/07/2016 Protocol reviewed by Medical Oncology Reference Committee via email
No changes
Next review in 5 years
16/10/2016 Patient information sheet updated to include more fluorouracil toxicity symptom warnings.
09/11/2016

The following change made post Medical Oncology Reference Committee meeting held on 21 October 2016: link to AGTIG and ANZCTR added.
04/05/2017 Discussion with Medical Oncology Reference Committee regarding fluorouracil dose, and 'maximum dose of 2000 mg/day' for fluorouracil removed from treatment schedule as no longer appropriate.
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.
16/02/2018 Fluoropyrimidine warning added. 
10/05/2018 Haematological dose modifications updated as per consensus of the expert clinician group. Fluorouracil toxicity profile in clinical information removed. Version number changed to V.4.

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

Send feedback for this page

First approved:
Last reviewed:
Review due:
As required

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/81

06 Oct 2024