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COVID-19: Obtenez les dernières mises à jour ou faites une autoévaluation.

Les traitements par chimiothérapie et autres traitements systémiques pourraient être modifiés en raison de la COVID-19. Vous trouverez de plus amples renseignements à la page Traitements systémiques pendant la pandémie de la COVID-19.

Certaines de ces informations ou toutes, dans certains cas, n’apparaissent qu’en Anglais. Vous pouvez demander la version française

A - Regimen Name

FULCVR Regimen
Fluorouracil-Leucovorin


Disease Site
Gastrointestinal - Colorectal

Intent
Adjuvant

Regimen Category
Evidence-Informed :

Regimen is considered appropriate as part of the standard care of patients; meaningfully improves outcomes (survival, quality of life), tolerability or costs compared to alternatives (recommended by the Disease Site Team and national consensus body e.g. pan-Canadian Oncology Drug Review, pCODR).  Recommendation is based on an appropriately conducted phase III clinical trial relevant to the Canadian context OR (where phase III trials are not feasible) an appropriately sized phase II trial. Regimens where one or more drugs are not approved by Health Canada for any indication will be identified under Rationale and Use.


Rationale and Uses

Adjuvant therapy of stage III colon cancer.

 
B - Drug Regimen

leucovorin
20 mg /m² IV (give before fluorouracil) Days 1 to 5
fluorouracil
400-425 mg /m² IV Days 1 to 5
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C - Cycle Frequency

REPEAT EVERY 28 DAYS

For a Usual Total of 6 Cycles

 
D - Premedication and Supportive Measures

Antiemetic Regimen:

Low


Febrile Neutropenia Risk:

Low

Other Supportive Care:

May advise patients to suck on ice chips during bolus injection, to reduce stomatitis

Also refer to CCO Antiemetic Recommendations.

 
E - Dose Modifications

Doses should be modified according to the protocol by which the patient is being treated.

Consider testing for DPD deficiency before starting treatment, based on local availability and guidelines.

Dosage with toxicity

Fluorouracil:

Toxicity or Counts (x 109/L)

During Cycle

For Next cycle

 

Platelets < 80 or ANC < 1.5

Hold*

May consider ↓ 

Bleeding, febrile neutropenia

Hold*

↓ by 25% 

≥ grade 3 GI

Hold*

↓ by 25% 

≥ grade 3 Hand-Foot Syndrome Hold* ↓ by 25% 

CNS

Hold*

↓ by 25% 

Cardiac

Hold*

Consider discontinuing 

* Do not retreat until ANC ≥ 1.5 x 109/L , platelets ≥ 100 x 109/L and organ toxicity ≤ grade 2.  With severe toxicity, consider testing for DPD deficiency prior to rechallenge.

Leucovorin:   No adjustment required. Omit if fluorouracil is discontinued. 



Hepatic Impairment

No dose adjustment required for leucovorin. Consider fluorouracil dose reduction with moderate to severe hepatic impairment.

Suggested:

Bilirubin
 
AST/ALT
Fluorouracil (% previous dose)

< 2 x ULN

and

3-5 x ULN

75 %

2-4 x ULN

or

5-10 x ULN

50-75%

> 4 x ULN

or

> 10 x ULN

Discontinue

Renal Impairment

No adjustment required for fluorouracil or leucovorin, although fluorouracil dose reduction may be considered with severe renal insufficiency.


Dosage in the Elderly

Elderly patients are at a higher risk of developing toxicities, likely due to lower bone marrow reserve.


 
F - Adverse Effects

Refer to leucovorin, fluorouracil drug monograph(s) for additional details of adverse effects.

Bolus 5FU regimens have more myelosuppression and GI effects but less Hand-Foot Syndrome, compared to prolonged infusions.


Very common (≥ 50%)

Common (25-49%)

Less common (10-24%)

Uncommon (< 10%),

but may be severe or life-threatening

  • Myelosuppression ± infection, bleeding (may be severe)
  • ECG changes (mostly asymptomatic)
  • Nausea, vomiting
  • Diarrhea (may be severe)
  • ↑ Bilirubin (may be severe)
  • Mucositis (may be severe)
  • Conjunctivitis / tearing
  • Rash / dry skin
  • Photosensitivity
  • Anorexia
  • Alopecia
  • Hand-foot syndrome
  • Arrhythmia
  • Cardiotoxicity
  • Arterial / venous thromboembolism
  • Radiation recall reaction
  • Hemolysis
  • Hypersensitivity
  • Leukoencephalopathy
  • Acute cerebellar syndrome
  • Extrapyramidal / cortical dysfunction
  • Oculomotor disturbances, optic neuritis
  • Tear duct fibrosis
  • GI ulceration
  • Hepatic necrosis
 
G - Interactions

Refer to fluorouracil, leucovorin drug monograph(s) for additional details


  • Use of fluorouracil within 4 weeks of treatment with brivudine, sorivudine (and chemically related analogues) is contraindicated.
  • Thiazide diuretics may decrease renal excretion of fluorouracil; consider an alternative antihypertensive.
  • Monitor INR closely while on concomitant warfarin; adjust warfarin dose accordingly.
  • Monitor phenytoin levels if used concurrently with fluorouracil.
  • Avoid concomitant use of metronidazole if possible.
  • Caution with the concurrent use of cimetidine due to interference with fluorouracil metabolism; fatal cases have been reported.
 
H - Drug Administration and Special Precautions

Refer to fluorouracil, leucovorin drug monograph(s) for additional details


Administration

Fluorouracil:

  • Slow push through sidearm of free-flowing IV (5% Dextrose, Normal Saline)
  • May be mixed in 50mL minibag (NS or D5W); infuse over 15 min.
  • Store at room temperature (15-25ºC).  Protect from light.


Leucovorin:

  • Doses ≤100mg may be given by IV push through sidearm of free flowing IV (5% Dextrose, Normal Saline).  The injection must not exceed 160mg/min of leucovorin (due to calcium content).
  • May be mixed in 50mL Normal Saline or 5% Dextrose minibag (doses up to 500mg). Give over 15 minutes.
  • Leucovorin should not be mixed in the same infusion as 5-fluorouracil as a precipitate may form.
  • Keep refrigerated; do not freeze.  Protect from light.


Contraindications

  • patients with poor nutritional state
  • patients with depressed bone marrow function (prior pelvic irradiation / marrow infiltration)
  • patients with potentially serious infections
  • patients with known hypersensitivity to the drug or any of its excipients
  • patients with known complete absence of dihydropyrimidine dehydrogenase (DPD) activity. 
  • fluorouracil should not be taken within 4 weeks of treatment with brivudine, sorivudine or their chemically related analogues.


Other Warnings/ Precautions

  • Use with extreme caution in patients who:
    • have undergone recent major surgery,
    • have renal or hepatic impairment,
    • have widespread bone marrow involvement,
    • have previous use of other myelosuppressive chemotherapeutic agents,
    • have a history of high dose irradiation to bone marrow-bearing areas, 
    • have a history of heart disease,
    • or are suspected to have DPD deficiency.
       
  • Avoid the use of live vaccines.
     
  • Uridine triacetate is a specific antidote for treating fluorouracil overdose or severe early-onset toxicities. It should be given within 96 hours after the end of the fluorouracil infusion.


Pregnancy and Lactation

  • FULCVR is contraindicated in pregnancy and breastfeeding. Appropriate contraception should be used by both sexes during treatment, and for at least 6 months after the last dose (generic recommendation).
  • Fertility effects:  Probable
 
I - Recommended Clinical Monitoring

Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.

Recommended Clinical Monitoring

  • CBC; Baseline and before each cycle
  • Liver function tests; Baseline and before each cycle
  • Renal function tests; Baseline and before each cycle
  • Clinical assessment and grading of stomatitis, diarrhea, bleeding, infection, local site toxicity, skin effects (rash or hand-foot-syndrome), cardiovascular or ophthalmic effects, and neurotoxicity; At each visit
  • Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version

Suggested Clinical Monitoring

  • INR in patients taking warfarin; baseline and as clinically indicated

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J - Administrative Information

Approximate Patient Visit
0.5 hour
Pharmacy Workload (average time per visit)
10.742 minutes
Nursing Workload (average time per visit)
40 minutes
 
K - References

Fluorouracil, leucovorin drug monographs, Cancer Care Ontario.

International Multicentre Pooled Analysis of Colon Cancer Trials Investigators. Efficacy of adjuvant fluorouracil and folinic acid in colon cancer. Lancet 1995. 345:939-44.


June 2020 updated Dose Modifications, Adverse Effects, Drug Administration and Special Precautions, Interactions and Monitoring sections


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M - Disclaimer

Regimen Abstracts
A Regimen Abstract is an abbreviated version of a Regimen Monograph and contains only top level information on usage, dosing, schedule, cycle length and special notes (if available). It is intended for healthcare providers and is to be used for informational purposes only. It is not intended to constitute or be a substitute for medical advice, and all uses of the Regimen Abstract are subject to clinical judgment. Such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability, and Cancer Care Ontario disclaims all liability for the use of this information, and for any claims, actions, demands or suits that arise from such use.
Information in regimen abstracts is accurate to the extent of the ST-QBP regimen master listings, and has not undergone the full review process of a regimen monograph.  Full regimen monographs will be published for each ST-QBP regimen as they are developed.
Regimen Monographs
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.