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A - Regimen Name

EPIRIFOS Regimen
EPIrubicin-Ifosfamide


Disease Site
Sarcoma - Soft Tissue

Intent
Adjuvant

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

Intensified adjuvant chemotherapy treatment for Soft Tissue Sarcoma.

 
B - Drug Regimen

ifosfamide

(Round to nearest 25 mg)
1800 mg /m² IV Day 1 to 5
mesna

(Round to nearest 1 mg)
360 mg /m² IV immediately before Ifosfamide infusion, then 4 and 8 hours post-infusion Days 1 to 5
EPIrubicin

(Round to nearest 1 mg)
60 mg /m² IV Days 1 and 2
filgrastim
300 mcg SC per day Daily on days 8 to 15
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C - Cycle Frequency

REPEAT EVERY 21 DAYS

For a usual total of 5 cycles, or until evidence of disease progression or limited by drug toxicity

 
D - Premedication and Supportive Measures

Antiemetic Regimen:

Moderate


Febrile Neutropenia Risk:

High

Other Supportive Care:

  • Ifosfamide:
  • Oral hydration is strongly encouraged; poorly hydrated patients may need more IV hydration.
  • Inadequate total hydration may result in dose-related hemorrhagic cystitis
 
E - Dose Modifications

Doses should be modified according to the protocol by which the patient is being treated. The following recommendations are in use at some centres.

Dosage with toxicity

Hematologic Toxicities:  See Appendix 6 for general recommendations.



Hepatic Impairment

 

Bilirubin        
  AST / ALT
Actions
1 - 2 x ULN
and/or 2 - 4 x ULN
REDUCE Epirubicin to 50% dose
2 – 4 x ULN
and/or > 4 x ULN
REDUCE Epirubicin to 25%-50% dose
> 4 x ULN
and/or OMIT
Omit dose
The dose of ifosfamide should be adjusted in the presence of hepatic impairment.

Renal Impairment

Clearance or Creatinine Levels
Actions
If CrCl <0.5mL/sec or
     Serum Creatinine > 185µmol/L
REDUCE Ifosfamide to 75 % dose
If CrCl <0.2mL/sec or
     Serum Creatinine >300µmol/L
REDUCE Ifosfamide to 67 % dose

 
F - Adverse Effects

Refer to ifosfamide, mesna, EPIrubicin, filgrastim drug monograph(s) for additional details of adverse effects


Most Common Side Effects 

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

  • Alopecia
  • Dysgeusia
  • Mucositis
  • Nausea, vomiting
  • Fatigue
  • Diarrhea
  • Abdominal pain
  • Hemorrhagic cystitis
  • Neurotoxicity (may be severe)
  • Flu-like symptoms
  • Myelosuppression +/- infection, bleeding (may be severe)
  • Bone pain
  • Hypersensitivity
  • Arrhythmia
  • Cardiotoxicity
  • Arterial thromboembolism
  • Venous thromboembolism
  • Pneumonitis
  • Pancreatitis
  • Rhabdomyolysis
  • Vision changes
  • SIADH
 
G - Interactions

Refer to ifosfamide, mesna, EPIrubicin, filgrastim drug monograph(s) for additional details

 
H - Drug Administration and Special Precautions

Refer to ifosfamide, mesna, EPIrubicin, filgrastim drug monograph(s) for additional details

 
I - Recommended Clinical Monitoring

Recommended Clinical Monitoring

  • CBC; baseline and before each cycle.
  • Baseline and regular liver function tests.
  • Baseline and regular renal function tests (including electrolytes and magnesium) and urinalysis.
  • Cardiac examination especially with risk factors (including prior therapy with doxorubicin, mitoxantrone, or other cardiotoxic drug), or a cumulative epirubicin dose of > 900 mg/m2.
  • Clinical toxicity (including stomatitis, neurotoxicity, cystitis, local toxicity, cardiotoxicity) assessment; at each visit
  • Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version


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J - Administrative Information

Approximate Patient Visit
4.5 hours
Pharmacy Workload (average time per visit)
31.2 minutes
Nursing Workload (average time per visit)
54.667 minutes
 
K - References

Epirubicin, ifosfamide, mesna drug monographs, Cancer Care Ontario.

Frustaci S, Gherlinzoni F, De Paoli A, et al. Adjuvant chemotherapy for adult soft tissue sarcomas of the extremities and girdles: results of the Italian ramomized cooperative trial.
J of Clin Oncol 2001;19(5): 1238-47.

October 2017 Replaced regimen category with evidence-informed


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L - Other Notes

Sarcomas are rare tumours and as such benefit from referral to specialized centres where there will be access to multidisciplinary expertise including good radiology, orthopedic and thoracic surgery, medical oncology, radiation oncology, pathology, and other supportive care disciplines.

 
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.