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.
MTRX
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.
Treatment for recurrent and/or metastatic head and neck cancer
| methotrexate | 40 mg /m² | IV | Day 1 |
|
(If no toxicity at 40mg/m2, may increase by 10mg/m2 q2weeks (maximum 60 mg/m² IV on Day 1) |
|||
REPEAT EVERY 7 DAYS
Until evidence of disease progression or limited by toxicity to chemotherapy
Dosage with toxicity
| Toxicity |
Action
|
|
Grade 4 neutropenia or thrombocytopenia, febrile neutropenia or thrombocytopenic bleeding |
Hold until recovery* and then reduce by 25% |
|
Grade 3 non-hematologic/organ |
Hold until recovery* and then reduce by 25% |
|
Grade 4 non-hematologic/organ |
Discontinue
|
|
Suspected pneumonitis
|
Hold, investigate appropriately and discontinue of confirmed |
|
Leukoencephalopathy, hepatic fibrosis, viral reactivation |
Discontinue
|
|
* until ANC ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L and other toxicity ≤ grade 2 |
|
Hepatic Impairment
|
Bilirubin (µmol/L) |
Transaminases |
% usual dose |
|
|
2.5 - 4 x ULN |
or | > 3 x ULN |
75% |
|
> 4 x ULN |
DISCONTINUE |
Renal Impairment
Methotrexate is contraindicated in patients with severe renal impairment. The following are recommended starting doses in patients with renal impairment. May require further dose adjustment due to wide inter-subject variability in pharmacokinetics.
|
Creatinine clearance (mL/min) |
Starting dose (% usual dose) |
|
>80 |
100% |
|
80 |
75% |
|
60* |
60% |
|
50 |
55% |
|
<50 |
Use alternative therapy |
Dosage in the Elderly
Methotrexate has not been well studied in the elderly. It should be used with extreme caution because of likely renal and hepatic impairment and reduced folate stores in the elderly. Monitor closely.
Refer to methotrexate drug monograph(s) for additional details on adverse effects.
|
More Common Side Effects (≥ 10%) |
Less Common Side Effects, but may be |
|
|
Refer to methotrexate drug monograph(s) for additional details
- Contraindicated with concomitant use of nitrous oxide anesthesia or acitretin.
- Avoid concurrent use with hepatotoxic drugs (e.g. leflunomide, retinoids, azathioprine, sulfasalazine).
- Consider adjusting methotrexate dose if used together with cyclosporine or theophylline; monitor for toxicity.
- Caution with concomitant use or proton pump inhibitors and low-dose methotrexate, due to reduced renal elimination of methotrexate or its metabolite; consider use of H2 antagonists.
- Thiazide diuretics, including triamterene, may increase the risk of myelosuppression; consider alternative antihypertensive therapy.
Refer to methotrexate drug monograph(s) for additional details
Administration
- Do not admix with 5FU, prednisolone, KCl or other drugs unless compatibility data are available.
- Avoid contact with acidic solutions since methotrexate precipitation may occur.
- May be given by IV push.
- Store unopened vials between 15 to 25⁰C. Protect from light
Contraindications
- Patients who are hypersensitive to methotrexate or any components of the formulation or container
- Patients with severe renal impairment including end stage renal disease with and without dialysis
- Women of childbearing potential until pregnancy is excluded
- Breastfeeding women
- Concomitant use with nitrous oxide anesthesia
- Formulations containing benzyl alcohol are contraindicated for use in intrathecal, intracerebroventricular, high-dose therapy, or neonates (less than one month of age)
Refer to the product monograph for contraindications related to the treatment of psoriasis or rheumatoid arthritis.
Warning / Precautions
- Use with extreme caution in patients with a history of peptic ulceration or ulcerative colitis and in patients with poor performance status, with active infection, impaired bone marrow function, prior or current wide field radiation, chronic liver disease, cirrhosis or with mild or moderate renal impairment.
- Avoid the use of live vaccines.
- Immunization may be ineffective when given during methotrexate treatment.
- Rare hypogammaglobulinemia has been reported.
- Not recommended in patients with active or chronic hepatitis B or C infection.
- Folate deficiency states may increase methotrexate toxicity.
- Patients with relevant third space fluid collections have prolonged excretion of methotrexate levels and a resulting increase in toxicity. Evacuation of fluid collections and close monitoring of serum levels are recommended in such patients.
- There may be an increased risk of tissue necrosis or osteonecrosis when methotrexate is given concurrently with radiotherapy
Pregnancy/ lactation
- Methotrexate is contraindicated in pregnancy and breastfeeding. It has been reported to cause fetal death and/or congenital anomalies. Abortion is likely when administered to a pregnant woman.
- Adequate contraception should be used in both sexes, during treatment and for at least for 6 months after the last dose.
- Effects on fertility: Yes
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 dose
- Liver function tests; baseline and as clinically indicated
- Renal function tests; baseline and as clinically indicated
- Chest x-ray; baseline and as clinically indicated
- Clinical assessment of infection, bleeding, GI (stomatitis, diarrhea), skin, pulmonary or CNS toxicity; at each visit
-
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
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Forastiere AA, Metch B, Schuller DE, et al, Randomized comparison of cisplatin plus fluorouracil and carboplatin plus fluorouracil versus methotrexate in advanced squamous-cell carcinoma of the head and neck: A Southwest Oncology Study. J Clin Oncol, 1992; 10: 1245-51.
Hong WK, Schaefer S, Issell B, et al. A prospective randomized trial of methotrexate versus cisplatin in the treatment of recurrent squamous cell carcinoma of the head and neck. Cancer 1983;52(2):206-10.
Methotrexate drug monograph, Ontario Health (Cancer Care Ontario).
Stewart JS, Cohen EE, Licitra L, et al. Phase III study of gefitinib compared with intravenous methotrexate for recurrent squamous cell carcinoma of the head and neck. J Clin Oncol 2009;27(11):1864-71.
November 2022 Updated Antiemetic category, Dosage in renal impairment, Adverse effects, Interactions, Drug administration and special precautions, Clinical monitoring sections
Methotrexate regimen is associated with low toxicity risks and response rates of about 10-15% but no difference in survival when compared against 5FU and Cisplatin.
In patients with adequate performance status where standard chemotherapy would unlikely yield a good therapeutic index, consideration should be made for enrollment into a clinical trial of novel agent(s).
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.