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Colorectal adjuvant Roswell Park (modified) fluorouracil and leucovorin weekly

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

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
Calcium folinate (Leucovorin) 50 mg * IV bolus 1, 8, 15, 22, 29, 36
Fluorouracil 500 mg/m2 IV 1, 8, 15, 22, 29, 36

* This is a "modified" Roswell Park regimen as the dose of calcium folinate (Leucovorin®) in this protocol has been modified from the original clinical trial dose of 500 mg/m2 to 50 mg based on reference committee consensus. Refer to discussion on calcium folinate (Leucovorin®) and evidence section for more information. 

Frequency:
56 days (weekly for six weeks followed by a two week break)
Cycles:
3 
Drug status:

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

Cost:
~ $520 per cycle "How this cost is calculated"

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

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

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

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

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

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

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

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

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

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

Cycle 1 to 3

Day 1, 8, 15, 22, 29, 36
Metoclopramide 10 mg (PO)

one tablet when necessary (maximum of 30 mg/24 hours, up to 5 days)
Calcium folinate (Leucovorin) 50 mg (IV bolus) over 1 to 2 minutes
Fluorouracil 500 mg/m2 (IV) over 3 to 5 minutes

This is a "modified" Roswell Park regimen as the dose of calcium folinate (Leucovorin®) in this protocol has been modified from the original clinical trial dose of 500 mg/m2 to 50 mg based on reference committee consensus. Refer to discussion on calcium folinate (Leucovorin®) and evidence section for more information. 

Frequency:
56 days (weekly for six weeks followed by a two week break)
Cycles:
3 

Cycle 1 to 3

Drug Dose Route Day
Calcium folinate (Leucovorin) 50 mg * IV bolus 1, 8, 15, 22, 29, 36
Fluorouracil 500 mg/m2 IV 1, 8, 15, 22, 29, 36

* This is a "modified" Roswell Park regimen as the dose of calcium folinate (Leucovorin®) in this protocol has been modified from the original clinical trial dose of 500 mg/m2 to 50 mg based on reference committee consensus. Refer to discussion on calcium folinate (Leucovorin®) and evidence section for more information. 

Frequency:
56 days (weekly for six weeks followed by a two week break)
Cycles:
3 
Drug status:

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

Cost:
~ $520 per cycle "How this cost is calculated"

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

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

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

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

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

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

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

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

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

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

Cycle 1 to 3

Day 1, 8, 15, 22, 29, 36
Metoclopramide 10 mg (PO)

one tablet when necessary (maximum of 30 mg/24 hours, up to 5 days)
Calcium folinate (Leucovorin) 50 mg (IV bolus) over 1 to 2 minutes
Fluorouracil 500 mg/m2 (IV) over 3 to 5 minutes

This is a "modified" Roswell Park regimen as the dose of calcium folinate (Leucovorin®) in this protocol has been modified from the original clinical trial dose of 500 mg/m2 to 50 mg based on reference committee consensus. Refer to discussion on calcium folinate (Leucovorin®) and evidence section for more information. 

Frequency:
56 days (weekly for six weeks followed by a two week break)
Cycles:
3 
  • Adjuvant colorectal cancer.
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 required

IV cannula (IVC) or central venous access device (CVAD) is required to administer this treatment.

Read more about central venous access device line selection
Emetogenicity LOW

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
Severe enteropathy associated with fluoropyrimidine

Severe enteropathy has been reported among patients with stage ll/lll colon cancer treated with fluoropyrimidine chemotherapy with or without oxaliplatin. Patients treated with fluoropyrimidine should be closely monitored for diarrhoea and aggressively managed.

Read more about severe enteropathy associated with fluorouracil in colorectal cancer
Diarrhoea

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

Read more about treatment induced diarrhoea
Growth factor support

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

Access the PBS website opens in a new tab or window
Blood tests

FBC, EUC, eGFR and LFTs 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. 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.
  • The dose of calcium folinate (Leucovorin®) remains fixed at 50 mg and is delayed or omitted if fluorouracil bolus is delayed or omitted.
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 fluorouracil by 25% for subsequent cycles
Febrile neutropenia Delay treatment until recovery and consider reducing 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 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)		 Fluorouracil
≥ 60

Full dose
45 - 59

Full dose

Increased risk of adverse events
30 - 44

Full dose

Increased risk of adverse events
15 - 29

Full dose

Increased risk of adverse events
< 15
(without kidney replacement therapy)		 Consult a multidisciplinary team consisting of oncology/haematology with nephrology and/or clinical pharmacology for the management of dosing.
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 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
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

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.

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
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, 8, 15, 22, 29 and 36

Approximate treatment time: 30 minutes

Pre treatment assessment

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

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

Prior to administration

Prime IV line(s).

Insert IV cannula or access TIVAD or CVAD.

Pre treatment medication

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

Calcium folinate (leucovorin)

Administer calcium folinate (leucovorin):
  • by IV bolus via a side port of the IV line over 1 to 2 minutes
  • flush with ~ 50mL of sodium chloride 0.9%.

Fluorouracil

  • If using oral cryotherapy commence ~ 5 minutes prior to administering fluorouracil and continue for ~ 30 minutes post.rr
Administer fluorouracil (irritant):
  • over 3 to 5 minutes
    • via a minibag OR
    • by IV bolus via a side port of a freely flowing IV infusion
  • flush with ~ 100 mL of sodium chloride 0.9%. 

Post administration

Remove IV cannula and/or deaccess TIVAD or CVAD. 

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

Discharge information

Discharge medications

Antiemetics - as/if prescribed.

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
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.
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
Diarrhoea

Read more about treatment induced diarrhoea
Ocular changes

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

Increased sensitivity to ultraviolet (UV) light resulting in an exaggerated sunburn-like reaction accompanied by stinging sensations and urticaria.
Fatigue

Read more about fatigue
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

Late (onset weeks to months)
Anaemia

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

Read more about anaemia
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
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

Due to the lack of conclusive evidence to identify the optimum dose of calcium folinate (Leucovorin®), it is the consensus of the eviQ reference committee to adopt flat dosing of calcium folinate (Leucovorin®) as a 50 mg IV bolus when used with bolus 5FU across all colorectal and upper gastrointestinal protocols. A discussion regarding the effect of dosing on outcome can be found in the calcium folinate (Leucovorin®) dose document.

The weekly fluorouracil (5-FU) plus leucovorin regimen, also commonly referred to as the Roswell Park regimen was evaluated for its efficacy by the National Surgical Adjuvant Breast and Bowel Project (NSABP C-03 trial) in patients with Duke's B and C colorectal cancer.r

Between August 1987 and April 1989, a total of 1081 patients were enrolled into the study and randomly assigned to receive either 5-FU 325 mg/m2/day day 1-5 and 375 mg/m2/day day 36-40, lomustine 130 mg/m2 on day 1 and vincristine 1 mg/m2 (max 2mg) on days 1 and 36 or 5-FU 500 mg/m2 and leucovorin 500 mg/m2 weekly for 6 weeks followed by 2 weeks break.

The primary end points of the study were disease-free survival and overall survival.r

In a more recent phase III trial (NSABP C-07), the efficacy of 3 cycles of the weekly Roswell Park regimen, FU 500 mg/m2 plus LV 500 mg/m2 weekly for 6 weeks for three 8-week cycles (FULV) was compared to 3 cycles of the the same FULV regimen with oxaliplatin 85 mg/m2 administered on week 1, 3, and 5 of each 8 week-cycle (FLOX).r The addition of oxaliplatin showed a disease-free survival benefit (HR, 0.82; 95% CI, 0.72 to 0.93; p=0.002). However, there was no statistically significant difference in overall survival (HR, 0.88; 95% CI, 0.75 to 1.02; p=0.08).r

Efficacy

After a follow-up of 3 years, the DFS rate and OS rate for 5-FU/FA versus MOF were 73% vs 64% and 84% vs 77% respectively. This translates to a 30% and 32% risk reduction in treatment failure and mortality respectively in patients receiving 5-FU/FA compared to MOF.r

Disease-free survivalr

© Journal of Clinical Oncology 1993

Overall survivalr

© Journal of Clinical Oncology 1993

Toxicity

Toxicityr FULV FLOX p-value
Grade 3 4 3 4
Diarrhoea 32 <1 37 1 0.003
Dehydration 11 <1 16 1 < 0.001
Nausea 11 0 16 0 < 0.001
Vomiting 8 <1 12 < 1 < 0.001
Fatigue 3 <1 5 < 1 0.15
Neurosensory <1 0 8 0 < 0.001
Thrombosis or embolism 4 1 3 1  0.78

© Journal of Clinical Oncology 2007

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Version 6

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

Version 5

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.5.

Version 4

Date Summary of changes
08/10/2019 Clinical information updated with PBS expanded indications for GCSF.
20/10/2022

Protocol reviewed electronically by Medical Oncology Reference Committee. No changes. Next review 4 years.

Version 3

Date Summary of changes
25/11/2012 New protocol taken to medical oncology reference committee meeting.
27/03/2012 Approved and published on eviQ.
03/04/2012 PHC OMIS view added.
13/09/2013 Protocol reviewed at medical oncology reference committee.
Group consensus not to supersede as protocol is still being used.
No changes and next review in 2 years.
24/08/2014 PHC view removed.
18/02/2016 Discussion with medical oncology reference committee Chairs and protocol to be reviewed every 5 years. Next review due in 3 years.
16/10/2016 Patient information sheet updated to include more fluorouracil toxicity symptom warnings.
09/11/2016 The following changes made post medical oncology reference committee meeting held on 21 October 2016. Link to AGTIG and ANZCTR added. Sentence in dose modifications regarding omitting leucovorin if fluorouracil is delayed or omitted changed to specify fluorouracil bolus.
31/05/2017 Transferred to new eviQ website. Version number change to V.2.
16/02/2018 Protocol reviewed electronically by medical oncology reference committee. Fluoropyrimidine warning added. Review in 5 years.
10/05/2018 Haematological dose modifications updated as per consensus of the expert clinician group. Version number changed to V.3.
25/09/2018 Treatment schedule note and evidence section updated with Leucovorin® dosing information as per reference committee consensus.

The information contained in this protocol is based on the highest level of available evidence and consensus of the eviQ reference committee regarding their views of currently accepted approaches to treatment. Any clinician (medical oncologist, haematologist, radiation oncologist, medical physicist, radiation therapist, pharmacist or nurse) seeking to apply or consult this protocol is expected to use independent clinical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. While eviQ endeavours to link to reliable sources that provide accurate information, eviQ and the Cancer Institute NSW do not endorse or accept responsibility for the accuracy, currency, reliability or correctness of the content of linked external information sources. Use is subject to eviQ’s disclaimer available at www.eviQ.org.au

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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/1271

12 May 2025