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Certaines de ces informations ou toutes, dans certains cas, n’apparaissent qu’en Anglais. Vous pouvez demander la version française

A - Regimen Name

ECX Regimen
EPIrubicin-CISplatin-XELODA ® (Capecitabine )


Disease Site
Gastrointestinal - Esophagus
Gastrointestinal - Gastric / Stomach

Intent
Adjuvant
Neoadjuvant

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

An alternative to ECF in the neoadjuvant (perioperative) / adjuvant settings for treating patients with potentially curable, surgically resectable (Stage 1B and above) gastric cancer. In Cunningham et al (2006), ECF was used in patients with adenocarcinoma of the stomach or lower third of the esophagus, stage II or higher with no evidence of distant metastases, or locally advanced inoperable disease, with WHO performance status 0 or 1 and who had no previous chemotherapy or radiotherapy.


Supplementary Public Funding

capecitabine
ODB - General Benefit (capecitabine)

 
B - Drug Regimen

EPIrubicin
50 mg /m² IV Day 1
CISplatin
60 mg /m² IV Day 1
capecitabine
625 mg /m² PO BID* days 1 to 21
(*Total daily dose 1250 mg/m2/day; outpatient prescription in 150mg and 500mg tablets)
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C - Cycle Frequency

REPEAT EVERY 21 DAYS

Perioperative: For 6 cycles (3 prior to and 3 after surgery) in the absence of disease progression or unacceptable toxicity

 
D - Premedication and Supportive Measures

Antiemetic Regimen:

High
No routine prophylaxis for capecitabine


Febrile Neutropenia Risk:

Moderate

Other Supportive Care:

  • Standard regimens for Cisplatin premedication and hydration should be followed. Refer to local guidelines.
  • Topical emollients (e.g. hand creams, udder balm) may ameliorate the manifestations of hand-foot syndrome in patients receiving capecitabine.
  • Supportive care should be provided, including loperamide for diarrhea.
 
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.

Use capecitabine with extreme caution in patients with partial DPD deficiency; reduce the initial dose substantially, monitor frequently and adjust the dose for toxicity as recommended in the dosage with toxicity section. In patients with unrecognized DPD deficiency, acute, life-threatening toxicity may occur; discontinue if acute grade 2-4 toxicity develops.

Dosage with toxicity

Worst Toxicity Grade/
Counts (x 109/L) in Prior Cycle

Epirubicin (% previous dose)

Cisplatin Dose (% previous dose)

Capecitabine
Febrile Neutropenia
Thrombocytopenic bleeding
Grade 4 ANC ≥ 7 d
Hold, then ↓ 75%*
 

Refer to table below.

Cardiotoxicity**

Discontinue

No change

Grade 3 related non-hematologic/organ

Hold, then ↓ 75%* for suspect drug

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 1009/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%.

 
 
 
Capecitabine:
 
Patients should be informed of the need to interrupt treatment immediately if moderate or severe toxicity occurs.  Doses should not be re-escalated if reduced for toxicity. Missed or omitted doses of capecitabine should not be replaced.

Dose modifications are mandatory for gastrointestinal, dermatological toxicity and hyperbilirubinemia.  Practitioner may elect not to reduce dose for other toxicities unlikely to become serious or life-threatening.

 

 

 

Toxicity
Action During a Course of Therapy
Dose Adjustment for Next Cycle  (% of starting dose)
 
 
Grade 1
 
 
Maintain dose level
 
Maintain dose level
 
Grade 2
1st appearance
2nd appearance
3rd appearance
4th appearance
 
 
 
Interrupt until resolved to grade 0-1
Interrupt until resolved to grade 0-1
Interrupt until resolved to grade 0-1 Discontinue treatment permanently
 
 
100%
75%
50%
--
 
Grade 3
1st appearance
2nd appearance
3rd appearance OR any evidence of Stevens-Johnson syndrome or Toxic Epidermal Necrolysis
 
 
Interrupt until resolved to grade 0-1
Interrupt until resolved to grade 0-1
Discontinue treatment permanently
 
 
75%
50%
--
 
Grade 4
 
1st appearance, including SJS/TEN, OR
cardiotoxicity OR
acute renal failure
 
 
 
 
2nd appearance
 
 

Discontinue permanently
                 or
If physician deems it to be in the patient’s best interest to continue and no evidence of Stevens-Johnson syndrome or toxic epidermal necrolysis, interrupt until resolved to grade 0-1.
 

Discontinue permanently
 
 
 
Discontinue
or
 
50%
 
 
 
 
--
 



Hepatic Impairment

Bilirubin
 
AST
Epirubicin
Cisplatin
Capecitabine

1-2 x ULN

Or

2-4 x ULN

↓ to 50% dose

No change

Refer to the dose modification table for Capecitabine

2-4 x ULN

Or

> 4 x ULN

↓ to 25% dose

> 4 x ULN

 
 
OMIT

Renal Impairment

Creatinine clearance (mL/min)
Epirubicin
Cisplatin
Capecitabine

> 50

 
 No change

No change

No change (monitor closely)

30-50
50%

↓ to 75% dose (use with caution)

10-<30

Consider ↓ dose

Discontinue or ↓ 50%

Omit

< 10

↓ dose

Discontinue

 
F - Adverse Effects

Refer to EPIrubicin, CISplatin, capecitabine 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
  • Cardiotoxicity, hypertension
  • Stomatitis,diarrhea, anorexia
  • Hand foot syndrome
  • Vesicant
  • Fatigue
  • ↑ LFTs
  • Myalgia, arthralgia
  • Rash (may be severe); photosensitivity
  • Reproductive risks
  • Radiation recall reaction
  • Hypersensitivity
  • Seizures
  • Acute encephalopathy, ocular toxicity/neuritis
  • Thrombotic microangiopathy
  • Acute leukemia
  • Arterial and venous thromboembolism
  • SIADH
  • Raynauds
  • Arrhythmia
  • Cardiotoxicity
 
G - Interactions

Refer to EPIrubicin, CISplatin, capecitabine drug monograph(s) for additional details

 
H - Drug Administration and Special Precautions

Refer to EPIrubicin, CISplatin, capecitabine drug monograph(s) for additional details

 
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 at each visit
  • Liver and renal function tests (including electrolytes and magnesium); baseline and regular
  • INR if on anticoagulants; baseline and regular
  • Cardiac examination especially with risk factors (including prior therapy with doxorubicin, mitoxantrone or other cardiac drug), or a cumulative epirubicin dose of > 650 mg/m2
  • Clinical toxicity assessment (including diarrhea, infection, stomatitis, hand-foot-syndrome, ototoxicity, local toxicity, neurotoxicity); at each visit

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

Suggested Clinical Monitoring

  • Audiogram; periodic
     

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J - Administrative Information

Approximate Patient Visit
Day 1: 4 hours
Pharmacy Workload (average time per visit)
41.231 minutes
Nursing Workload (average time per visit)
61.667 minutes
 
K - References

Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 2006;355(1):11-20.

Epirubicin, cisplatin, capecitabine drug monographs, Cancer Care Ontario.

August 2019 removed archived PEBC guideline link


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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.