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.
GDP
Hematologic - Lymphoma - Non-Hodgkin's Intermediate Grade
Palliative
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.
For treatment of relapsed or refractory aggressive non-Hodgkin's lymphoma.
The clinical trial by Crump et al included patients with ECOG status 0 to 3; patients with diffuse large B-cell lymphoma who had received one previous anthracycline-containing chemotherapy regimen; and patients with DLBCL transformed from follicular or other indolent-histology lymphoma had received ≤ 3 previous treatments, with at least one anthracycline-containing regimen. Patients were cisplatin and gemcitabine naïve prior to treatment.
dexamethasone
ODB - General Benefit
(dexamethasone)
(ODB Formulary)
| gemcitabine | 1000 mg /m² | IV | Days 1 and 8 |
| CISplatin | 75 mg /m² | IV | Day 1 |
| dexamethasone | 40 mg | PO | Days 1 to 4 |
|
(Outpatient prescription in 4mg tablets) |
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REPEAT EVERY 21 DAYS
- If complete or partial response occurs after 2 cycles, may proceed to autologous stem cell transplant (ASCT). May receive a third cycle if patient has not achieved a complete or partial response after 2 cycles.
- Patients with stable disease who were not candidates for stem cell transplant or patients who had any response after 2-3 cycles of GDP may receive up to 6 cycles of treatment.
High (D1)
Low (D8)
Moderate
Other Supportive Care:
-
The day 1 dexamethasone dose can be given IV before chemotherapy to prevent emesis, with the oral treatment dose reduced accordingly.
-
Consider use of filgrastim to maintain dose intensity for patients with febrile neutropenia or prolonged neutropenia.
-
Standard regimens for Cisplatin premedication and hydration should be followed. Refer to local guidelines.
Also refer to CCO Antiemetic Recommendations.
Doses should be modified according to the protocol by which the patient is being treated. The following recommendations have been adapted from the LY.12 study (Crump et al, 2014).
Dosage with toxicity
Dose adjustments are to be made based on the system showing the greatest degree of toxicity. Doses held during a cycle of therapy do not need to be made up. All doses should go back to 100% of the planned dose for the next cycle, unless otherwise indicated below.
Table 1: Dosage with Hematologic Toxicities
|
Day(s) of Cycle |
Absolute Neutrophil Count (ANC) (x109/L) |
|
Platelets (x109/L) |
Action This Cycle |
|
Day 1 |
≥ 1.0 |
AND |
≥ 75 |
Give 100% dose of all drugs |
|
≥ 1.0 |
AND |
< 75 |
Delay 1 week* If platelets then ≥ 75, give 100% dose of all drugs. If platelets still < 75 but ≥ 50, give 100% dose rather than delay further; support with platelet transfusions as necessary. |
|
|
< 1.0 |
AND |
≥ 75 |
Delay 1 week* If ANC then ≥ 1.0, give 100% of all drugs. If ANC still < 1.0 but ≥ 0.5, give 100% dose rather than delay further; initiate GCSF. **
|
|
|
< 1.0 |
AND |
< 75 |
Delay 1 week*
OR
|
|
|
Day 8 |
≥ 1.0 |
AND |
≥ 75 |
Give 100% dose of gemcitabine |
|
≥ 0.5 and < 1.0 |
AND |
≥ 75 |
Give 100% dose gemcitabine and initiate GCSF* OR 75% of day 1 dose |
|
|
---- |
|
< 75 and |
75% of day 1 dose |
|
|
< 0.5 |
OR |
< 50 |
Omit gemcitabine dose this cycle and initiate GCSF ** |
|
|
* If counts presumed to be low due to marrow involvement, treat after 1-‐week delay (i.e. at 4 weeks or Day 28) despite counts. |
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Table 2: Dosage with Non-Hematologic Toxicities
Serum creatinine must be ≤ 1.5 X ULN and bilirubin ≤ 1.5 X ULN prior to treatment at full dose. Refer to table below for dosing with elevated creatinine or bilirubin
If the toxicity is believed to be due to dexamethasone, then discontinue dexamethasone for that cycle and re-‐assess for future cycles.
|
Day(s) of Cycle |
Worst grade in previous period |
Gemcitabine |
Cisplatin |
|
|
Day 1 |
Hypersensitivity/ acute reactions grade 1-2 |
Hold causal agent for 1 hour then resume at 50% rate; monitor carefully |
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|
Hypersensitivity/acute reactions grade 3 |
Hold causal agent for 1 hour then resume at 50% rate. Monitor carefully If recurs discontinue causal agent |
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|
Hypersensitivity/acute reactions grade 4 |
Discontinue causal agent |
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|
> Grade 2 pneumonitis |
Hold, if confirmed, discontinue |
100% |
||
|
Grade 3 other toxicity *
|
75% |
75% |
||
|
Creatinine |
1.5 – 3.0 x ULN |
100% |
75% (for this and all future cycles) |
|
|
> 3.0 x ULN |
Hold for one week; if recovers to ≤ 3 x ULN modify dose as above. If not discontinue |
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|
Bilirubin > |
1.5 – 3.0 x ULN |
75% (for this and all future cycles) |
100% |
|
|
|
> 3.0 x ULN |
Hold for one week; if recovers to ≤ 3 x ULN modify dose as above. If not, discontinue |
||
|
Grade 4 |
Hold one week. If toxicity does not resolve to level acceptable for dose reduction (see above), discontinue treatment. |
|||
|
Day 8 |
< Grade 2 |
100% |
n/a |
|
|
> Grade 2 pneumonitis |
Hold, if confirmed, discontinue |
n/a |
||
|
Grade 3 other toxicity ** |
75% of day 1 dose |
n/a |
||
|
Grade 4 |
Hold |
n/a |
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|
* Except nausea, vomiting, and alopecia; In the event of grade 3 tinnitus, reduce cisplatin dose only. ** Patient may receive a dose reduction or discontinue treatment. This decision will depend upon the type of non-‐hematologic toxicity seen and is at the discretion of the treating physician. |
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Hepatic Impairment
See Table 2 above.
Renal Impairment
Dosage in the elderly:
Geriatric patients may be at higher risk of developing nephrotoxicity, ototoxicity/neurotoxicity or hematologic adverse effects with cisplatin. Gemcitabine clearance is lower in the elderly but no dose adjustment necessary.
Dosage based on gender:
Gemcitabine clearance is lower in women but no dose adjustment is necessary.
Refer to gemcitabine, CISplatin, dexamethasone drug monograph(s) for additional details of adverse effects
| Most Common Side Effects |
Less Common Side Effects, but may be |
|
|
Refer to gemcitabine, CISplatin, dexamethasone drug monograph(s) for additional details
- Avoid nephrotoxic and ototoxic drugs (i.e. aminoglycosides) due to additive effects.
- Concomitant use of renally excreted drugs (i.e. methotrexate) may decrease renal clearance and enhance toxicities of these drugs. Avoid use, if possible. If not possible, modify doses as necessary.
- Cisplatin may decrease phenytoin levels; monitor levels and patient.
- Gemcitabine may increase INR and bleeding risk in patients taking warfarin; monitor closely and adjust INR as needed
Refer to gemcitabine, CISplatin, dexamethasone drug monograph(s) for additional details
Administration
Gemcitabine:
- Dilute reconstituted drug in normal saline for IV infusion; to a minimum final concentration of 0.1 mg/mL.
- Infuse over 30 minutes through free-flowing IV.
Cisplatin:
- Ensure good urinary output during chemotherapy visit. Patient should void at least once during chemotherapy visit. Use locally approved hydration regimens.
- Blood pressure should be taken before and after chemotherapy.
- Additional hydration may be ordered for hypovolemic patients.
- Hydration and diuresis for patients with pre-existing renal, cardiac, or diabetic history at discretion of physician.
- Oral hydration with 8 glasses of fluid per day is strongly encouraged on treatment day and for 1-2 days after cisplatin; if nausea and vomiting prevent oral hydration, the patient may need to return for more IV hydration.
- Cisplatin is physically incompatible with any IV set, needle or syringe containing aluminum.
- Store unopened vials between 15°C to 25°C and protect from light. Do not refrigerate or freeze since precipitation will occur
Contraindications
- Patients with known hypersensitivity to gemcitabine or platinum containing compounds
Other Warnings/Precautions
- All patients should receive appropriate hydration and antiemetic protocols according to local guidelines.
- Gemcitabine use in patients with impaired hepatic function, including concurrent liver metastases or a previous history of hepatitis, alcoholism or liver cirrhosis may lead to exacerbation of the hepatic insufficiency
- Cisplatin and gemcitabine are not recommended for use in pregnancy or breastfeeding. Appropriate contraception should be used by both sexes during treatment, and for at least 6 months after the last dose
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
- Audiogram; Baseline and as clinically indicated
- Electrolytes, including magnesium, sodium, potassium, phosphate and calcium; Baseline and before each dose
- CBC; Baseline and before each dose
- LFTs; baseline and before each cycle
- Renal function tests; Baseline and before each dose
- Clinical assessment of hypersensitivity reactions, tumour lysis syndrome, flu-like symptoms, infection, bleeding, GI (including nausea/vomiting), neurotoxicity, ototoxicity, thromboembolism, pulmonary, skin, CNS, cardiovascular side effects; At each visit
-
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
Suggested Clinical Monitoring
Audiogram; Periodic
Liver function tests; Baseline and regular
INR for patient receiving warfarin; Baseline and regular
Urinalysis; Baseline and regular
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Cisplatin and gemcitabine drug monographs, Cancer Care Ontario.
Crump M, Baetz T, Couban S, et al. Gemcitabine, dexamethasone, and cisplatin in patients with recurrent or refractory aggressive histology b-cell non-hodgkin lymphoma. Cancer 2004;101(8):1835-42.
Crump M, Sherpherd K, Lin B. A randomized phase III study of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin as salvage chemotherapy followed by posttransplantation rituximab maintenance therapy versus observation for treatment of aggressive B-Cell and T-Cell non-Hodgkin's lymphoma. Clin Lymphoma 2005; 6(1): 56-60.
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.