Les renseignements du Formulaire de médicaments s’adressent aux professionnels de la santé. Il ne s’agit pas d’un avis médical. Certains des renseignements, y compris ceux sur le financement des médicaments anticancéreux, ne s’appliquent pas à tous les patients. Les plans de traitement du cancer sont propres à chaque patient. Si vous êtes un patient, veuillez parler avec votre équipe soignante pour comprendre comment ces renseignements s’appliquent à vous.
CAPEDOCE
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.
Treatment of anthracycline resistant metastatic breast cancer. (Due to the toxicity level of the regimen, it should be used in younger patients with good performance status.)
capecitabine
ODB - General Benefit
(capecitabine)
| DOCEtaxel | 75 mg /m² | IV | Day 1 |
| capecitabine | 1000 mg /m² | PO | BID, Days 1 to 14 |
|
(Total capecitabine dose 2000 mg/m2/day) |
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REPEAT EVERY 21 DAYS
Until evidence of disease progression or unacceptable toxicity
Low
No routine prophylaxis for capecitabine
Other Supportive Care:
- Dexamethasone 8 mg bid po for 3 days starting 1 day prior to docetaxel (prevent anaphylaxis / fluid retention.)
- 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.
Doses should be modified according to the protocol by which the patient is being treated. Practitioner may elect not to reduce dose for toxicities unlikely to become serious or life-threatening.
Patients should be tested for DPD deficiency before starting treatment with capecitabine. Refer to the DPD Deficiency Guidance for Clinicians for more information.
In patients with unrecognized DPD deficiency, acute, life-threatening toxicity may occur; if acute grade 2-4 toxicity develops, treatment should be stopped immediately and permanent discontinuation considered based on clinical assessment of the toxicities.
The beginning of a cycle should be delayed until neutrophil count is ≥ 1.5 x 109/L, platelets ≥100 x 109/L and patient has recovered from severe toxicity in the previous cycle. In general, doses reduced for toxicity should not be re-escalated. However, if docetaxel is permanently discontinued, and toxicity with capecitabine as a single agent is ≤ grade 1, consider escalation of the capecitabine dose to standard dosing by increments of 25%.
Dosage with toxicity
Table A: Hematologic Toxicity
|
Toxicity and Grade
|
Within a Cycle |
Day 1 of subsequent cycle |
|
|
|
Capecitabine
|
Capecitabine
|
Docetaxel Dose |
|
Grade 3 or 4 neutropenia only
|
Monitor
|
No change1
|
No change1
|
|
Grade 3 or 4 neutropenia with ≥ grade 2 non-hematological toxicity |
Hold until ≤ grade 1
|
No change1. Refer to table below for non-hematological toxicity.
|
No change1. Refer to table below for non-hematological toxicity.
|
|
Grade 4 neutropenia ≥ 7 days/ febrile neutropenia
|
Hold until neutrophils ≥1.5 x 109/L |
No change1, or consider dose modification
|
55mg/m2 (1). If recurs, discontinue
|
For first appearance of cystoid macular edema, hold docetaxel and investigate; refer patient promptly to an ophthalmic examination. Discontinue docetaxel if confirmed.
|
|
Grade 2 |
Grade 3 |
Grade 4 |
||
|
Docetaxel |
Capecitabine |
Docetaxel |
Capecitabine |
|
|
|
1st appearance |
Hold until ≤ grade 1. |
Hold until ≤ grade 1. |
Hold until ≤ grade 1 then ↓ to 55mg/m2. Discontinue if > 2wk delay or grade 3 toxicities recur. |
Hold until ≤ grade 1 then give 75% of original dose. |
Discontinue docetaxel and capecitabine. If deemed appropriate by the physician and no evidence of SJS/TEN^, may continue with single agent capecitabine at 50% of original dose. |
|
Discontinue if any evidence of SJS ^. |
|||||
|
2nd appearance |
Hold until ≤ grade 1, then ↓ to 55mg/m2 |
Hold until ≤ grade 1, then give 75% of original dose |
Discontinue |
Hold until ≤ grade 1, then give 50% of original dose |
Discontinue |
|
3rd appearance |
Discontinue |
Hold until ≤ grade 1, then give 50% of original dose |
Discontinue |
Not applicable |
|
|
4th appearance |
Discontinue |
Not applicable |
Not applicable |
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Hepatic Impairment
|
Bilirubin
|
AST or ALT
|
|
ALP
|
Capecitabine
|
Docetaxel
% Starting Dose
|
|
≤ ULN
|
≤ 1.5 x ULN
|
AND
|
≤ 2.5 x ULN
|
Use with caution; no adjustment required
|
100%
|
|
≤ ULN
|
>1.5 – 3.5 X ULN
|
AND
|
>2.5 to 6 X ULN
|
Do not treat
|
|
|
≤ ULN
|
> 3.5 ULN
|
OR
|
> 6 X ULN (unless bone ONLY)
|
No information found; consider dose reduction or discontinue
|
Do not treat. Discontinue if treatment already started. |
|
> ULN
|
|
|
|
Follow Table B
|
Do not treat. Discontinue if treatment already started.
|
Renal Impairment
Mild-moderate renal impairment results in increased exposure to capecitabine metabolites and an increase in severe toxicity.
| CrCl (mL/min) | Capecitabine (% Starting Dose) | Docetaxel (% Starting Dose) |
| 51-80 | 100% | 100% |
| 30-50 | 75% (use with caution) | 100% |
| <30 | Discontinue | 100% |
Dosage in the Elderly
For capecitabine, dose adjustment for the starting dose is not required, but patients should be closely monitored and dose modification should be performed as described above. Older patients are more susceptible to the effects of fluoropyrimidine-based therapies with increased grade 3 / 4 adverse effects, especially when used in combination.
For docetaxel, no adjustment required, but caution should be exercised in elderly patients with poor performance status who are receiving docetaxel. Patients over the age of 60 years appear to have increased toxicity when docetaxel is used in combination with capecitabine.
Refer to capecitabine, DOCEtaxel drug monograph(s) for additional details of adverse effects
| Most Common Side Effects |
Less Common Side Effects, but may be |
|
|
Refer to capecitabine, DOCEtaxel drug monograph(s) for additional details
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
- INR and/or PT; Baseline and regular if on anticoagulants
- Liver function tests; Baseline and routine
- Renal function tests; Baseline and regular
- Regular toxicity assessment of infection, bleeding, fatigue, neurotoxicity, GI (e.g. diarrhea, stomatitis), dehyration, fluid retention, hypersensitivity, cutaneous reactions, hand-foot syndrome, thromboembolism, cardiovascular, musculoskeletal pain, ophthalmic, respiratory effects; at each visit
-
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
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Capecitabine and docetaxel drug monographs, Cancer Care Ontario.
Chan S, Romieu G, Huober J.. Phase III study of gemcitabine plus docetaxel compared with capecitabine plus docetaxel for anthracycline-pretreated patients with metastatic breast cancer. J Clin Oncol 2009;27(11):1753-60.
Leonard R, O’Shaughnessy J, Vukelja S, et al. Detailed analysis of a randomized phase III trial: can the tolerability of capecitabine plus docetaxel be improved without compromising its survival advantage? Annals of Oncology 2006: 17; 1379–85.
O'Shaughnessy J, Miles D, Vukelja S, et al. Superior Survival With Capecitabine Plus Docetaxel Combination Therapy in Anthracycline-Pretreated Patients With Advanced Breast Cancer: Phase III Trial Results JCO, June 15, 2002 :2812-1823.
April 2023 Updated DPD deficiency information in the Dose Modifications section
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.