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.
CISPFU+TRAS
Gastric / Stomach
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.
For the palliative treatment of HER2-overexpressing (IHC3+ or IHC2+ confirmed by ISH) inoperable advanced (non-resectable; either locally advanced, recurrent or metastatic) adenocarcinoma of the stomach or the gastroesophageal junction, in patients who are ECOG 0-2, have a normal ejection fraction and have not received previous systemic treatment for metastatic disease.
trastuzumab
New Drug Funding Program
(Trastuzumab (Biosimilar) - Advanced Gastric, Gastroesophageal, or Esophageal Cancer)
Note: Different trastuzumab products are NOT INTERCHANGEABLE
Trastuzumab Loading Dose:
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trastuzumab 1 | 8 mg /kg | IV | Day 1, cycle 1 only |
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THEN, Trastuzumab Maintenance Dose: |
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trastuzumab 1
| 6 mg /kg | IV | Day 1, cycle 2 onwards |
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1In general, the dose of trastuzumab should be delayed if the chemotherapy cycle is delayed for scheduling convenience; if the delay is > 1 week, trastuzumab loading dose should be repeated. AND |
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| CISplatin | 80 mg /m² | IV | Day 1 |
| fluorouracil | 800 mg /m²/day | IV over 24 hours as continuous infusion | Days 1 to 5 |
An alternative schedule for fluorouracil is 1000 mg/m2/day IV over 24 hours as continuous infusion, on days 1 to 4.
REPEAT EVERY 21 DAYS
Cisplatin-Fluorouracil: Up to 6 cycles unless evidence of disease progression or unacceptable toxicity occurs
Trastuzumab: Until evidence of disease progression or unacceptable toxicity
High
Other Supportive Care:
- To prevent recurrence of infusion-associated reactions, acetaminophen and diphenhydramine may be given as pre-medication. Refer to trastuzumab drug monograph for full details.
- Standard regimens for cisplatin premedication and hydration should be followed. Refer to local guidelines
- Fluorouracil: Topical emollients (e.g. hand creams, udder balm) or oral pyridoxine therapy may ameliorate the manifestations of hand-foot syndrome in patients; Supportive care should be provided, including loperamide for diarrhea.
Also refer to CCO Antiemetic Recommendations.
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 grade 2-4 acute toxicity develops, treatment should be stopped immediately and permanent discontinuation considered based on clinical assessment of the toxicities.
Dosage with toxicity
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Worst Toxicity Grade/
Counts (x 109/L) in Prior Cycle |
Cisplatin Dose (% previous dose)
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Fluorouracil (5FU) (% previous dose) |
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Grade 4 platelets, grade 4 ANC ≥ 5 days, Febrile Neutropenia, Thrombocytopenic bleeding
Grade 4 ANC ≥ 7 d
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75%* for suspect drug
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Grade 2 neurotoxicity / ototoxicity |
75%
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No change |
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Grade 3 or 4 neurotoxicity / ototoxicity |
Discontinue
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No change |
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Cardiotoxicity**
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No change
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Discontinue
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Grade 3 related non-hematologic/organ |
75%* for suspect drug. Consider discontinuing cisplatin. |
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Grade 4 related non-hematologic/organ |
Discontinue
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**including any signs and symptoms of heart failure, greater than 10% decline in LVEF to below the lower limit of normal, a greater than 20% decline in LVEF from any level, or LVEF ≤ 45%.
Trastuzumab:
Dosage with myelosuppression: No adjustment required.
(Continued on next page)
Dosage with cardiotoxicity - Product Monograph recommendations
- Trastuzumab should be held with a fall in LVEF (product monograph suggests if LVEF falls ≥10 points from baseline and/or if LVEF falls to < 50%). Repeat LVEF in 3 weeks and consider discontinuing. Discontinue if clinically significant cardiac dysfunction or cardiac failure develops.
Dosage with cardiotoxicity - Canadian Consensus Guidelines
- Discontinue if symptomatic.
Management of trastuzumab therapy in adjuvant breast cancer patients with asymptomatic decreases in LVEF (Mackey et al 2008):
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Relationship of LVEF to Lower Limit of Normal (LLN) |
Trastuzumab dose modification based on asymptomatic LVEF decrease from baseline |
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≤ 10 percentage points |
10-15 percentage points |
≥ 15 percentage points |
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Within facility’s normal limits |
Continue |
Continue |
Hold and repeat MUGA/ECHO after 4 weeks |
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1-5% below LLN |
Continue 1 |
Hold and repeat MUGA/ECHO after 4 weeks 1, 2 |
Hold and repeat MUGA/ECHO after 4 weeks 2, 3 |
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≥ 6% below LLN |
Continue and repeat MUGA/ECHO after 4 weeks 3 |
Hold and repeat MUGA/ECHO after 4 weeks 2, 3 |
Hold and repeat MUGA/ECHO after 4 weeks 2, 3 |
1 Consider cardiac assessment and starting ACEI therapy
2 After 2 holds, consider permanent trastuzumab discontinuation
3 Start ACEI therapy and refer to cardiologist
Dosage with other toxicity - Trastuzumab:
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Toxicity |
Action |
Comment |
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Mild hypersensitivity |
Decrease infusion rate |
May consider re-challenge with premedication |
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Hypersensitivity (dyspnea, clinically significant hypotension) |
Hold |
May consider rechallenge with premedication |
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Pulmonary toxicity, severe or life-threatening hypersensitivity |
Discontinue permanently |
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Hepatic Impairment
No adjustment required for trastuzumab and cisplatin.
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Bilirubin
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AST
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5FU (% previous)
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1-2 x ULN |
Or
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2-4 x ULN |
Consider ↓ dose in moderate-severe hepatic impairment |
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2-4 x ULN |
Or
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> 4 x ULN |
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> 4 x ULN |
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OMIT
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Renal Impairment
| Creatinine clearance (mL/min) | Cisplatin (% previous dose) | 5FU (% previous dose) |
| > 60 | No change | No change |
| > 50-60 | 75%* | No change |
| 30-50 | 50%* | No change |
| 10-<30 | Discontinue* | Consider ↓ dose |
| < 10 | Discontinue* | ↓ dose |
Refer to trastuzumab, CISplatin, fluorouracil drug monograph(s) for additional details of adverse effects
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Most Common Side Effects
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Less Common Side Effects, but may be |
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Refer to trastuzumab, CISplatin, fluorouracil drug monograph(s) for additional details
Refer to trastuzumab, CISplatin, fluorouracil drug monograph(s) for additional details
NOTE: Different trastuzumab products are NOT INTERCHANAGEABLE.
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
- Clinical toxicity assessment (including mucositis, nausea/vomiting, neurotoxicity, ototoxicity, cardiotoxicity, infection, bleeding, skin and pulmonary toxicity, diarrhea, infusion reactions).
- CBC before each cycle.
- Electrolytes, including magnesium, sodium, potassium, phosphate and calcium; baseline and regular
- Baseline and regular liver and renal function tests (including electrolytes and magnesium).
- Baseline and regular cardiac assessment, including evaluation of left ventricular function (Echocardiogram or MUGA scan); more frequent with asymptomatic reductions in LVEF, q3 months during treatment and then q6 months after trastuzumab discontinuation x 2 years
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Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
Suggested Clinical Monitoring
- Audiogram; baseline and periodic
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Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 2010; 376(9742): 687-97.
April 2023 Updated DPD deficiency information in the Dose Modifications section and antidote information in Other Notes section.
Schedule pump teaching session BEFORE first day of infusion.
Antidote for Fluorouracil Overdose:
Uridine triacetate is a prodrug of uridine and is a specific antidote for treating fluorouracil overdose or severe early onset toxicities. If available, consider administering as soon as possible (i.e. within 96 hours) for suspected overdose. If not available, treatment is symptomatic and supportive.
For usage approval and supply, contact Health Canada’s Special Access Program (SAP) (Phone: 613-941-2108. On-call service is available for emergencies). Uridine triacetate (Vistogard®) is supplied by its manufacturer in the United States (Wellstat Therapeutics).
The recommended dosing and administration for uridine triacetate in patients ≥18 years is:
- 10 grams (1 packet of coated granules) orally every 6 hours for 20 doses in total, without regards to meals.
- Granules should not be chewed. They should be mixed with 3 to 4 ounces of soft foods such as applesauce, pudding or yogurt.
- The dose should be ingested within 30 minutes of preparation, followed by at least 4 ounces of water.
- Refer to the prescribing information on dose preparation for NG-tube or G-tube use.
Additional resources on the management of fluorouracil infusion overdose:
- Management of Fluorouracil Infusion Overdose Guideline (Alberta Health Services)
- Management of Fluorouracil Infusion Overdose at the BCCA - Interim Guidance (BC Cancer Agency)
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.