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.
BEND
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.
First-line monotherapy in CLL patients with:
- Binet Stage B or C and
- WHO performance status of ≤ 2 and
- Not medically fit for fludarabine-based regimens but could be treated with other options such as chlorambucil. The phase III trial included patients up to 75 years of age.
bendamustine
New Drug Funding Program
(Bendamustine - First Line - Chronic Lymphocytic Leukemia)
(NDFP Website)
(
Funded for single agent only
)
REPEAT EVERY 28 DAYS
For a maximum of 6 cycles in the absence of unacceptable toxicity or disease progression
Moderate
Other Supportive Care:
Also refer to CCO Antiemetic Summary
• Patients at risk of tumour lysis syndrome should have appropriate prophylaxis and be monitored closely.
Hypertension should be controlled prior to starting treatment
Pre-medication (only for patients with Grade 1 or 2 reactions with prior infusion):
- Analgesic/antipyretic (e.g. acetaminophen), corticosteroid and an antihistamine (e.g. diphenhydramine) should be considered in subsequent cycles.
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.
Do not retreat until ANC ≥ 1 x 109/L and platelets ≥ 75 x 109/L and non-hematologic toxicity recovered to ≤ Grade 1.
Dosage with toxicity
Dose re-escalation in subsequent cycles may be considered at the discretion of the treating physician.
Dose levels:100 mg/m2, 50 mg/m2, 25 mg/m2
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Toxicity
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Modification
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Grade 4 Hematologic toxicities
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Delay until ANC ≥ 1 x 109/L, platelets ≥ 75 x 109/L then reduce by 1 dose level
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≥ Grade 3 Hypersensitivity reaction
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Discontinue
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≥ Grade 2 clinically significant Non-hematologic toxicities;
≥ Grade 3 Non-hematologic toxicities
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Delay until recovered to ≤ grade 1, then reduce by one dose level
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Hepatic Impairment
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Bilirubin
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AST or ALT or ALP
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Bendamustine dose
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≤ 1.5 x ULN
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≤ 2.5 x ULN
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Caution
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> 1.5 x ULN
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> 2.5 x ULN
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Do not use
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Renal Impairment
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Creatinine Clearance (mL/min)
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Bendamustine dose
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>80
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100%
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40 - 80
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Caution
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< 40
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Do not use
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Dosage in the Elderly
No dose adjustment required. No clinically significant differences in efficacy and safety were observed in those aged 65 and older and younger patients.
Refer to bendamustine drug monograph(s) for additional details of adverse effects
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Very common (≥ 50%) |
Common (25-49%) |
Less common (10-24%) |
Uncommon (< 10%), but may be severe or life-threatening |
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Refer to bendamustine drug monograph(s) for additional details
- CYP1A2 inhibitors my increase bendamustine concentration and toxicity; use with caution
- CYP1A2 inducers (including cigarette smoking) may reduce bendamustine concentration and/or efficacy
Refer to bendamustine drug monograph(s) for additional details
Administration:
- CLL - infuse over 30 minutes
- Bendamustine infusions should be administered in a setting where full resuscitation facilities are immediately available, and under the close supervision of someone experienced and capable of dealing with severe infusion-related reactions.
- DO NOT administer as an IV push or bolus.
- Dilute to a final concentration of 0.2 - 0.6 mg/mL in 500 mL infusion bag of 0.9% sodium chloride or 2.5% dextrose/0.45% sodium chloride.
- Reconstituted solution must be transferred to infusion bag within 30 minutes of reconstitution.
- Administer bendamustine through a dedicated line.
- Compatible with PVC or polyethylene bags.
- Do not admix with other drugs.
Contraindications:
- Patients who have a hypersensitivity to this drug or any of its components (including mannitol)
- Patients with CrCl < 40 mls/min or moderate/severe hepatic impairment
- Patients with serious infections
Other warnings/precautions:
- Avoid live vaccines, since they may result in serious or fatal infections in patients immunocompromised by bendamustine.
- Avoid in patients with relapsed indolent NHL who did not tolerate prior therapies (including other alkylating agents)
- Use with caution in patients with hypertension and patients with mild renal and hepatic impairment
Pregnancy and lactation:
- Bendamustine is not recommended for use in pregnancy. Adequate contraception should be used by both sexes 2 weeks before, during treatment, and for at least 4 weeks after the last dose.
- Breastfeeding is not recommended
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
- Blood pressure; Baseline and before each dose
- Electrolytes, including sodium, potassium, magnesium and uric acid; Baseline and before each cycle
- Hepatitis B surface antigen; Baseline and as clinically indicated
- Liver function tests; Baseline and before each cycle
- Renal function tests; Baseline and before each cycle
- Clinical toxicity assessment for infection (including CMV and herpes zoster), renal, cardiac, hepatic and skin toxicity , infusion reactions and secondary malignancies; at each visit
-
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
Suggested Clinical Monitoring
- Blood glucose; Baseline and periodic
- ECG; As clinically indicated; periodic in the setting of cardiac disorders and electrolyte imbalances
- HIV status; Baseline
- CMV testing in febrile patients
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Bendamustine drug monograph, Cancer Care Ontario.
Knauf WU, Lissitchkov T, Aldaoud A, et al. Bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukaemia: updated results of a randomized phase III trial. Br J Haematol 2012;159(1):67-77.
Knauf WU, Lissichkov T, Aldaoud A, et al. Phase III randomized study of bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukemia. J Clin Oncol 2009;27(26):4378-84.
October 2017 added dosage in elderly; updated dose mods and adverse effects tables
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.