Les renseignements du Formulaire de médicaments s’adressent aux professionnels de la santé. Il ne s’agit pas d’un avis médical. Certains des renseignements, y compris ceux sur le financement des médicaments anticancéreux, ne s’appliquent pas à tous les patients. Les plans de traitement du cancer sont propres à chaque patient. Si vous êtes un patient, veuillez parler avec votre équipe soignante pour comprendre comment ces renseignements s’appliquent à vous.
FULCVR
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.
| leucovorin | 20 mg /m² | IV (give before fluorouracil) | Days 1 to 5 |
| fluorouracil | 400 to 425 mg /m² | IV | Days 1 to 5 |
Low
Other Supportive Care:
May advise patients to suck on ice chips during bolus injection, to reduce stomatitisAlso refer to CCO Antiemetic Recommendations.
Doses should be modified according to the protocol by which the patient is being treated.
Patients should be tested for DPD deficiency before starting treatment with fluorouracil. Refer to the DPD Deficiency Guidance for Clinicians for more information.
In patients with unrecognized DPD deficiency, acute, life-threatening toxicity may occur; if acute grade 2-4 toxicity develops, treatment should be stopped immediately and permanent discontinuation considered based on clinical assessment of the toxicities.
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.
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 |
|
|
|
|
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.
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. Refer to the DPD Deficiency Guidance for Clinicians for more information.
- 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. Refer to the DPD Deficiency Guidance for Clinicians for more information
- 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
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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Buroker TR, O’Connell MJ, Weiand HE et al. Randomized comparison of two schedules of flourouracil and leucovorin in the treatment of advanced colorectal cancer. J Clin Oncol 1994;12:14-20.
Choi CW, Choi IK, Seo JH, et al. Effects of 5-fluorouracil and leucovorin in the treatment of pancreatic-biliary tract adenocarcinomas. Am J Clin Oncol 2000;23(4):425-8.
Porta C, Moroni M, Nastasi G, et al. 5-Fluorouracil and d,l-leucovorin calcium are active to treat unresectable hepatocellular carcinoma patients: preliminary results of a phase II study. Oncology 1995;52(6):487-91.
Tetef M, Doroshow J, Akman S, et al. 5-Fluorouracil and high-dose calcium leucovorin for hepatocellular carcinoma: a phase II trial. Cancer Invest 1995;13(5):460-3.
April 2023 Updated DPD deficiency information in the Dose Modifications and Special Precautions sections
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.