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A - Regimen Name

ECF Regimen
EPIrubicin-CISplatin-Fluorouracil


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 advanced gastric, esophageal or gastroesophageal cancer. Approximately 7% of patients in one of the clinical trials have squamous carcinoma.

 
B - Drug Regimen

EPIrubicin
50 mg /m² IV Day 1
CISplatin
60 mg /m² IV Day 1
fluorouracil
200 mg /m²/day IV over 24 hours as continuous infusion For 21 days (starting on day 1)
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C - Cycle Frequency

REPEAT EVERY 21 DAYS

Until evidence of disease progression or limited by toxicity

 
D - Premedication and Supportive Measures

Antiemetic Regimen:

High

Other Supportive Care:

Standard regimens for Cisplatin premedication and hydration should be followed. Refer to local guidelines.

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.
See appendix 6 for general recommendations.

 

 

 

Dosage with toxicity

Worst Toxicity / Counts (x 109/L) in previous cycle
 
Worst Toxicity / Counts (x 109/L) in previous cycle
EPIrubicin
(% previous dose)
CISplatin
(% previous dose)
fluorouracil
(% previous dose)
Febrile neutropenia or Grade 4 ANC ≥ 7 days
Or
Thrombocytopenic bleeding
 Or
Platelets < 25
↓ 75%* for each suspect drug
 
Cardiotoxicity**
 
 
Discontinue
No change Discontinue

Grade 2 neurotoxicity

   

No change

75%

 

No change

 

Grade 3 neurotoxicity     No change Discontinue No change
Grade 3 related organ / non-hematologic
 
 
↓ 75%* for suspect drug(s)
Grade 4 related organ / non-hematologic, including stomatitis
Hemolysis, optic neuritis, arterial thromboembolism, severe hypersensitivity
 
 
Discontinue
 
*Do not start new cycle until toxicities have recovered to ≤ grade 2, 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%.
 
 
 
 
 
 
 
 



Hepatic Impairment

Bilirubin

 

AST/ALT

EPIrubicin

(% previous dose)

CISplatin

(% previous dose)

fluorouracil

(% previous dose)

1-2 x ULN

 Or

2-4 x ULN

50%

 No change

Consider ↓ dose in moderate to severe hepatic impairment

>2-4 x ULN

 Or

>4 x ULN

25%

 No change

 Consider ↓ dose in moderate to severe hepatic impairment

>4 x ULN

 

 

OMIT

 No change

 OMIT


Renal Impairment

Creatinine Clearance (mL/min)
EPIrubicin
(% previous dose)
CISplatin
(% previous dose)
fluorouracil
(% previous dose)
46-60
 No change
 75%
 No change
30-45                        
 No change
 50%
 No change
10-30
 Consider ↓ dose
 Discontinue
 Consider ↓ dose
<10
 ↓ dose
 Discontinue
 ↓ dose

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

Prolonged 5FU regimens have more hand-foot syndrome but less myelosuppression and GI effects compared to bolus infusions.

Most Common Side Effects 

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

  • Nausea and vomiting
  • Myelosuppression ± infection, bleeding (may be severe)
  • Cardiotoxicity (may be severe)
  • Stomatitis and diarrhea
  • Alopecia
  • Vesicant
  • Nephrotoxicity (may be severe)
  • Electrolyte abnormalities
  • Neurotoxicity and ototoxicity (may be severe)
  • Hand-foot syndrome
  • Anorexia
  • Hyperuricemia
  • Secondary malignancy
  • Arterial, venous thromboembolism
  • Arrhythmia
  • Hemolytic uremic syndrome, vasculitis
  • Seizures
  • Hypersensitivity
  • Raynaud's
  • Hemolysis
  • Leukoencephalopathy
  • ↑ LFTs

 

 
G - Interactions
Refer to EPIrubicin, CISplatin, fluorouracil drug monograph(s) for additional details
 
H - Drug Administration and Special Precautions
Refer to EPIrubicin, CISplatin, fluorouracil drug monograph(s) for additional details
 
I - Recommended Clinical Monitoring

Recommended Clinical Monitoring

  • CBC; baseline and regular
  • Liver function tests; baseline and regular
  • Renal function tests; baseline and regular
  • Cardiac tests for all patients with cardiac risk factors and epirubicin cumulative doses > 650mg/m2; periodic
  • Electrolytes, including magnesium, phosphate and calcium; baseline and regular
  • Audiogram; as clinically indicated
  • Clinical toxicity assessment (infection, bleeding, stomatitis, thromboembolism nausea/vomiting, diarrhea, hand-foot syndrome, cardiotoxicity, local toxicity, neurotoxicity, ototoxicity); at each visit
  • 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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J - Administrative Information

Approximate Patient Visit
Day 1: 4-5hours; Days 8, 15: 0.5 hour
 
K - References

Bamos A, Hill M, Cunningham D, et al. Epirubicin, cisplatin, and protracted venous infusion of 5-flourouracil for esophagogastric adenocarcinoma. Cancer 1996; 77: 1978-85.

Findlay M, Cunningham D, Norman A, et al. A phase II study in advanced gastro-esophageal cancer using epirubicin and cisplatin in combination infusion 5-fluorouracil (ECF). Annals of Oncology 1994; 5: 609-616.

Product Monograph: Pharmorubicin. Pfizer Canada Inc. Sept. 15, 2009.

Ross P, Nicolson M, Cunningham D, et al. Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) with epirubicin, cisplatin and PVI 5FU in advanced esophagogastric cancer. JCO 2002; 20(8); 1996-2004.

Waters JS, Norman A, Cunningham D, et al. Long-term survival after epirubicin, cisplatin and fluorouracil for gastric cancer: results of a randomized trial. British Journal of Cancer 1999; 80(1/2): 269-72.

Webb A, Cunningham D, Scarffe T et al. Randomized trial comparing epirubicin, cisplatin and fluorouracil versus fluorouracil, doxorubicin and methotrexate in advanced oesophago-gastric cancer. J Clin Oncol 1997; 15:261-267.


PEBC Advice Documents or Guidelines

June 2019 Updated emetic risk category


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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.