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A - Regimen Name

CAPEGEMC Regimen
Gemcitabine-Capecitabine


Disease Site
Gastrointestinal - Hepatobiliary / Liver / Bile Duct

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

Treatment of cholangiocarcinoma in patients who are not considered candidates for surgery with curative intent, but who are willing and able to tolerate treatment with chemotherapy. Phase III trials have not been conducted.


Supplementary Public Funding

capecitabine
ODB - General Benefit (capecitabine)

 
B - Drug Regimen

gemcitabine
1000 mg /m² IV Days 1 and 8
capecitabine
650 mg /m² PO BID* Days 1 to 14

(*Total daily dose 1300mg/m2/day; Outpatient prescription in 150mg and 500mg tablets)

 

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C - Cycle Frequency

REPEAT EVERY 21 DAYS

Until evidence of disease progression or unacceptable toxicity

 
D - Premedication and Supportive Measures

Antiemetic Regimen:

Low
No routine prophylaxis for capecitabine

Other Supportive Care:

  • 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.

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.

 

 

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

Gemcitabine - Dose on Day 1 of Cycle: 

Worst Toxicity in Previous Cycle
 
Dose for next cycle*
Non-hematologic
(related organ)
 
Hematologic
 
% Full Dose
Grade 3
or

Febrile neutropenia, thrombocytopenic bleeding 

 
75%*
 
 
              Grade 4
 
 
 

Consider discontinuing,

or ↓ to 75%*
 
Worst Toxicity in Previous Cycle (Continued) Dose for next cycle*
Non-hematologic
(related organ)
  Hematologic % Full Dose

Day 8/15 holds in > 1 cycle

 
75%*
  • Pneumonitis
  • Hemolytic Uremic Syndrome (HUS)
  • Stevens-Johnson syndrome (SJS)
  • Toxic epidermal necrolysis (TEN)
  • Capillary Leak Syndrome (CLS)
 
 
Discontinue
 
* Do not start new cycle until ANC ≥ 1500x 106/L, platelets ≥ 100,000 x 106/L and non-hematologic toxicity ≤ grade 2.

 

 

 


 

Gemcitabine - Dose on Day 8 of Cycle:

Toxicity on Day 8 of cycle

 
Non-hematologic

(related organ)

 
Hematologic

Gemcitabine

(% Full Dose)

AGC
(x 106/L)
 
Platelets
(x 106/L)
≤ grade 2
and
> 1000
and
> 100,000
100%
≤ grade 2
and
500-1000
 
or
50,000-100,000
Consider Omit
or ↓ to 75%
Grade 3 or 4
or
< 500
 
or
< 50,000
Omit, ↓ to 75% at restart (if applicable) for non-hematologic toxicity

Pneumonitis
HUS
SJS
TEN
CLS

 
-
 
-
Discontinue

Capecitabine:

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%
--
 
 
 
Toxicity (Continued) Action During a Course of Therapy Capecitabine Dose Adjustment for Next Cycle (% of starting dose)
 
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, TENS, 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%
 
 


-
Dose adjustment mandatory for gastrointestinal, dermatological toxicity and hyperbilirubinemia. Practitioner may elect not to reduce dose for other toxicities unlikely to become serious or life-threatening. Doses should not be re-escalated if reduced for toxicity.



Hepatic Impairment

Gemcitabine:  Use with caution in patients with hepatic impairment (cirrhosis, hepatitis, metastases, etc.); initial dose reduction should be considered if the patient is treated, especially in hyperbilirubinemia.  

Capecitabine: Use dose modification table above for increases in bilirubin.  In patients with mild to moderate hepatic impairment due to liver metastases exposure is increased, but no dose adjustment is necessary, although caution should be exercised. The use of capecitabine in patients with severe hepatic impairment has not been studied.

 

 


Renal Impairment

Creatinine clearance (mL/min) Gemcitabine (% previous dose) Capecitabine (% previous dose)
51-80 100% 100%
30-50 100% 75%
<30 Consider
discontinuing or ↓
Discontinue

 
F - Adverse Effects

Refer to gemcitabine, 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

  • Myelosuppression ± infection, bleeding
  • Fatigue, flu-like symptoms
  • Musculoskeletal pain
  • Rash (may be severe)
  • Edema
  • Proteinuria
  • Hand-foot syndrome
  • Stomatitis
  • Diarrhea
  • Edema & Proteinuria
  • Nausea or vomiting
  • Elevated LFTs (may be severe)
  • Pneumonitis/ARDS
  • Hemolytic-uremic syndrome
  • Arrhythmia
  • Cardiotoxicity
  • Venous/arterial thromboembolism
  • Capillary leak syndrome
  • Hypersensitivity
  • Vasculitis

 

 
G - Interactions
Refer to gemcitabine, capecitabine drug monograph(s) for additional details

Gemcitabine is a known radiosensitizer.
 
H - Drug Administration and Special Precautions

Refer to gemcitabine, 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 before each cycle and on day 8. Interim counts should be done in first cycle and repeated if dose modifications necessary.
  • Baseline and regular liver and renal function tests
  • Clinical toxicity assessment (flu-like symptoms, fatigue, edema, pulmonary, rash, hand-foot syndrome, diarrhea, dehydration, infection, bleeding, stomatitis); at each visit
  • INR or PT; baseline and regular if on anticoagulants
  • Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version


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J - Administrative Information

Approximate Patient Visit
0.75 hour
Pharmacy Workload (average time per visit)
22.85 minutes
Nursing Workload (average time per visit)
36.667 minutes
 
K - References

Capecitabine and gemcitabine drug monographs, Cancer Care Ontario.

Knox JJ, Hedley D, Oza A, et al. Combining gemcitabine and capecitabine in patients with advanced biliary cancer: a phase II trial. J Clin Oncol. 2005;23:2332-8.

Riechelmann RP, Townsley CA, Chin SN, et al. Expanded phase II trial of gemcitabine and capecitabine in advanced biliary tract cancer. Cancer 2007;110:1307–12.

May 2019 Updated emetic risk category


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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.
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