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

CISPFU+TRAS

Cancer Type: Gastrointestinal, Esophagus, Gastric / Stomach  Intent: Palliative
Regimen Category: Evidence-Informed
Funding:
New Drug Funding Program
    Trastuzumab (Biosimilar) - Advanced Gastric, Gastroesophageal, or Esophageal Cancer
A - Regimen Name

CISPFU+TRAS Regimen
CISplatin-Fluorouracil-Trastuzumab


Disease Site
Gastrointestinal - Esophagus
Gastrointestinal - Gastric / Stomach

Intent
Palliative

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

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.


Supplementary Public Funding

trastuzumab
New Drug Funding Program (Trastuzumab (Biosimilar) - Advanced Gastric, Gastroesophageal, or Esophageal Cancer)

 
B - Drug Regimen

Note: Different trastuzumab products are NOT INTERCHANGEABLE
 

Trastuzumab Loading Dose:

trastuzumab

1

8 mg /kg IV Day 1, cycle 1 only
 
 

THEN, Trastuzumab Maintenance Dose:

trastuzumab
1
6 mg /kg IV Day 1, cycle 2 onwards

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

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.

back to top
 
C - Cycle Frequency

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

 
D - Premedication and Supportive Measures

Antiemetic Regimen:

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.

 
E - Dose Modifications

Doses should be modified according to the protocol by which the patient is being treated. The following recommendations have been adapted from clinical trials or product monographs and could be considered.

Dosage with toxicity

Worst Toxicity Grade/

Counts (x 109/L) in Prior Cycle

Cisplatin Dose (% previous dose)

Fluorouracil (5FU) (% previous dose)

Grade 4 platelets, grade 4 ANC ≥ 5 days, Febrile Neutropenia,

Thrombocytopenic bleeding
Grade 4 ANC ≥ 7 d
 75%* for suspect drug

Grade 2 neurotoxicity / ototoxicity

75%

No change

Grade 3 or 4 neurotoxicity / ototoxicity

Discontinue

No change

Cardiotoxicity**
No change
Discontinue

Grade 3 related non-hematologic/organ

75%* for suspect drug. Consider discontinuing cisplatin.

Grade 4 related non-hematologic/organ

Discontinue
* Do not retreat until toxicity has recovered to ≤ grade 2, and platelets ≥ 100 x 109/L, and ANC ≥ 1.5 x 109/L.
**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):

Relationship of LVEF to Lower Limit of Normal (LLN)

Trastuzumab dose modification
based on asymptomatic LVEF decrease from baseline

≤ 10 percentage points

10-15 percentage points

≥ 15 percentage points

Within facility’s normal limits

Continue

Continue

Hold and repeat MUGA/ECHO after 4 weeks

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

≥ 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:

Toxicity

Action

Comment

Mild hypersensitivity

Decrease infusion rate

May consider re-challenge with premedication

Hypersensitivity (dyspnea, clinically significant hypotension)

Hold

May consider rechallenge with premedication

Pulmonary toxicity, severe or life-threatening hypersensitivity

Discontinue permanently

 



Hepatic Impairment

No adjustment required for trastuzumab and cisplatin. 

Bilirubin
 
AST
5FU (% previous)

1-2 x ULN

Or

2-4 x ULN

Consider ↓ dose in moderate-severe hepatic impairment

2-4 x ULN

Or

> 4 x ULN

> 4 x ULN

 
 
OMIT

Renal Impairment

No adjustment required for trastuzumab. 
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
*Upon the discretion of the prescriber, less dose reduction may be suggested.  

 
F - Adverse Effects
Refer to trastuzumab, CISplatin, fluorouracil drug monograph(s) for additional details of adverse effects

Most Common Side Effects 

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

  • Nausea and vomiting
  • Nephrotoxicity (may be severe)
  • Neurotoxicity (ototoxicity), electrolyte changes
  • Myelosuppression ± infection, bleeding (may be severe)
  • Cardiotoxicity (may be severe)
  • Mucositis, diarrhea, anorexia
  • Hand-foot syndrome
  • Fatigue
  • Headache, musculoskeletal pain
  • Rash (including photosensitivity)
  • Infusion related reaction (may be severe); fever, chills
  • Leukoencephalopathy, optic neuritis
  • Arterial thromboembolism
  • Venous thromboembolism
  • Raynaud’s
  • Arrhythmia
  • Pancreatitis
  • Pneumonitis
  • Hemolytic-uremic syndrome, hemolysis, vasculitis
  • Secondary malignancies
  • Injection site reaction
  • ↑ LFTs
  • Renal failure
 
G - Interactions
Refer to trastuzumab, CISplatin, fluorouracil drug monograph(s) for additional details
 
H - Drug Administration and Special Precautions

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


NOTE: Different trastuzumab products are NOT INTERCHANAGEABLE.

 
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

  • 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
  • Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version

Suggested Clinical Monitoring

  • Audiogram; baseline and periodic

back to top
 
J - Administrative Information

Approximate Patient Visit
First Cycle: 5 hours; Subsequent cycles: 4 hours
Pharmacy Workload (average time per visit)
32.713 minutes
Nursing Workload (average time per visit)
72.083 minutes
 
K - References

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.


PEBC Advice Documents or Guidelines

November 2019 Updated NDFP forms and interchangeability information in Drug Regimen and Drug Administration and Special Precautions section sections.


back to top
 
L - Other Notes

Schedule pump teaching session BEFORE first day of infusion.

 
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.