You are using an outdated browser. We suggest you update your browser for a better experience. Click here for update.
Close this notification.
Skip to main content Skip to search

COVID-19: Get the latest updates or take a self-assessment.

Screen for hepatitis B virus in all cancer patients starting systemic treatment. Find out more about hepatitis B virus screening and management.

Drug Formulary information is intended for use by healthcare professionals. It is not intended to be medical advice. Some of the information, including information about funding for cancer drugs, does not apply to all patients. Cancer treatment plans are unique to each patient. If you are a patient, please speak with your healthcare team to understand how this information applies to you.

A - Regimen Name

MTRX Regimen

Disease Site
Head and Neck


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

Treatment for recurrent and/or metastatic head and neck cancer

B - Drug Regimen

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)

back to top
C - Cycle Frequency

Until evidence of disease progression or limited by toxicity to chemotherapy

D - Premedication and Supportive Measures

Antiemetic Regimen:


E - Dose Modifications

Doses should be modified according to the protocol by which the patient is being treated. 
Evaluate any pre-existing hepatitis B and C before starting treatment.

Dosage with toxicity


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

Suspected pneumonitis

Hold, investigate appropriately and discontinue of confirmed

Leukoencephalopathy, hepatic fibrosis, viral reactivation


* until ANC ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L and other toxicity ≤ grade 2



Hepatic Impairment

Bilirubin (µmol/L)


% usual dose

2.5 - 4 x ULN

or > 3 x ULN


> 4 x ULN



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)










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.




F - Adverse Effects

Refer to methotrexate drug monograph(s) for additional details on adverse effects.

 More Common Side Effects (≥ 10%)

Less Common Side Effects, but may be
Severe or Life-Threatening

  • Nausea and vomiting
  • Mucositis
  • Anorexia
  • Dyspepsia
  • ↑ LFTs (may be severe)
  • Myelosuppression ± bleeding, infection (including opportunistic infection, viral reactivation)
  • Nephrotoxicity/proteinuria
  • Encephalopathy
  • Pneumonitis
  • Arterial thromboembolism
  • Venous thromboembolism
  • Stevens-Johnson syndrome
  • Toxic epidermal necrolysis
  • Erythema multiforme
  • Radiation skin reaction
  • Hypersensitivity
  • GI perforation
  • Pancreatitis
  • Tumour lysis syndrome
  • Vasculitis
  • Secondary malignancies


G - Interactions

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.
H - Drug Administration and Special Precautions

Refer to methotrexate drug monograph(s) for additional details


  • 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


  • 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
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 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

back to top
J - Administrative Information

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

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

back to top
L - Other Notes

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).

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.