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.
CISPRALT
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.
raltitrexed
New Drug Funding Program
(Raltitrexed - Advanced Malignant Pleural Mesothelioma (MPM))
(NDFP Website)
High
- Also refer to CCO Antiemetic Recommendations.
Screen for hepatitis B virus in all cancer patients starting systemic treatment. Refer to the hepatitis B virus screening and management guideline.
Other Supportive Care:
- All patients should receive adequate hydration and premedication for emesis, according to local guidelines.
Doses should be modified according to the protocol by which the patient is being treated.
Dosage with toxicity
Suggested Dose Levels:
| Dose Level | Raltitrexed Dose (mg/m2) | Cisplatin Dose (mg/m2) |
| 0 | 3 | 80 |
| -1 | 2.25 | 60 |
| -2 | 1.5 | 40 |
|
Toxicity Grade
|
Action1
|
Raltitrexed
|
Cisplatin
|
|||
|
Grade 3 neutropenia / thrombocytopenia
|
OR
|
grade 2 GI toxicity
|
Hold1
|
↓ 1 dose level
|
↓1 dose level
|
|
|
Grade 3 neutropenia / thrombocytopenia
|
AND
|
grade 3 GI toxicity
|
Hold1
|
Discontinue
|
↓ 1 dose level
|
|
|
Grade 4 neutropenia / thrombocytopenia
|
OR
|
grade 3 GI toxicity
|
Hold1
|
↓ 2 dose levels
|
↓ 2 dose levels
(If grade 3 GI only, ↓ 1 dose level if related to cisplatin)
|
|
|
|
|
grade 4 GI toxicity
|
Hold1
|
Discontinue
|
↓ 2 dose levels
|
|
|
Grade 2 Neurotoxicity
|
|
No change
|
↓ 50%
|
|||
|
Other ≥ grade 3 non-hematological
|
AND
|
1st occurrence
|
Hold1
|
↓ 1 dose level
|
↓ 1 dose level; discontinue if neurotoxicity
|
|
|
Grade 3 or 4 toxicity
|
AND
|
Recurrence after prior reduction
|
Discontinue
|
Discontinue
|
Discontinue
|
|
|
1 Retreat only when GI toxicity resolved, platelets are ≥ 100 x 109/L, ANC ≥ 2 x 109/L, and WBC ≥ 4 x 109/L.; consider discontinuing if major organ toxicity.
|
||||||
Management of Cisplatin Infusion-related Reactions:
Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.
There is insufficient evidence that routine prophylaxis with extended infusion reduces IR rates.
| Grade | Management | Re-challenge |
| 1 or 2 |
Restart:
|
|
| 3 or 4 |
|
|
* Up to 50% of patients can experience recurrent reactions during re-challenge despite using pre-medications (e.g. corticosteroid and H1/H2-receptor antagonist.
Hepatic Impairment
No dose adjustment required for cisplatin.
Raltitrexed:
|
Hepatic Impairment |
Starting Dose |
|
Mild to moderate |
No dose adjustment recommended. Use with caution. |
|
Severe |
Contraindicated |
Renal Impairment
Raltitrexed is contraindicated in severe renal impairment.
Mild to moderate renal impairment results in a significant reduction in raltitrexed clearance and doses must be modified for renal impairment. Patients with renal impairment should be monitored carefully.
|
Creatinine Clearance (mL/min)
|
Raltitrexed Dose as % of 3mg/m2
|
Raltitrexed Dosing Interval
|
Cisplatin
(% of previous dose)
|
|
> 65
|
100%
|
q3w
|
100%
|
|
55-65
|
75%
|
q4w
|
100%
|
|
25-54
|
% equivalent to mL/min*
|
q4w
|
75% or 50%
|
|
10 - <25
|
Contraindicated
|
Not Applicable
|
OMIT^
|
|
< 10
|
Dosage in the Elderly
Geriatric patients may be at higher risk of developing nephrotoxicity, ototoxicity/neurotoxicity, GI, or hematologic adverse effects. Use with caution.
Refer to raltitrexed, CISplatin drug monograph(s) for additional details of adverse effects.
|
Very common (≥ 50%) |
Common (25-49%) |
Less common (10-24%) |
Uncommon (< 10%), but may be severe or life-threatening |
|
|
|
|
Refer to raltitrexed, CISplatin drug monograph(s) for additional details.
- Nephrotoxic and ototoxic drugs may increase the risk of nephro and ototoxicity; avoid if possible or caution during or shortly after cisplatin therapy (for 1-2 weeks).
- Phenytoin levels may be altered by cisplatin. Monitor and adjust phenytoin dose as required.
- Avoid folinic or folic acid preparations immediately before or during raltitrexed administration, as this may interfere with raltitrexed action.
Refer to raltitrexed, CISplatin drug monograph(s) for additional details.
Administration
Raltitrexed:
-
Mix in 50-250 mL (NS, D5W); infuse IV over 15 minutes.
-
Do not admix with other drug.
-
Store unopened vials at 2 to 25°C protected from light.
- Reconstituted and diluted solutions do not need to be protected from light
CISplatin:
- Cisplatin is physically incompatible with any IV set, needle or syringe containing aluminum.
- All patients should receive adequate hydration and premedication for emesis, according to local guidelines.
- 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.
- Adequate hydration and urinary output must be maintained for 24 hours following cisplatin treatment.
- 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.
- Store unopened vials between 15°C to 25°C and protect from light. Do not refrigerate or freeze since precipitation will occur.
Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.
Contraindications
- Patients with known hypersensitivity to drugs in this regimen, platinum containing compounds, or any of their components
- Patients who are myelosuppressed
- Patients with severe renal and/or hepatic impairment
- Patients with pre-existing renal and hearing impairment, unless the potential benefits outweigh the risk
- Children < 18 years of age
Other warnings/precautions
- Caution is necessary in patients with poor general condition, prior radiotherapy, mild to moderate hepatic impairment and in elderly patients
Pregnancy/lactation:
- This regimen is contraindicated for use in pregnancy. Adequate contraception should be used by patients and their partners while on treatment and after the last treatment dose. Recommended methods and duration of contraception may differ depending on the treatment. Refer to the drug monograph(s) for more information.
- Breastfeeding is contraindicated during treatment and after the last treatment dose. Refer to the drug monograph(s) for recommendations after the last treatment dose (if available).
- Fertility effects: Yes
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
Refer to the hepatitis B virus screening and management guideline for monitoring during and after treatment.
Recommended Clinical Monitoring
- CBC; baseline and before each cycle. Interim counts should be done in first cycle and repeated if dose modifications necessary
- CBC, for patients who develop signs of GI toxicity; weekly
- Renal function tests; baseline and at each cycle
- Electrolytes, including magnesium, sodium, potassium, phosphate and calcium; Baseline and at each cycle
- Liver functions tests; baseline and at each cycle
- Audiogram; baseline and as clinically indicated
- Clinical toxicity assessment including bleeding, infection, injection site reactions, nausea/vomiting, diarrhea, neurologic, ototoxicity, fatigue, stomatitis, cutaneous effects, arterial and venous thromboembolism; at each visit
-
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
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Cisplatin drug monograph, Ontario Health (Cancer Care Ontario).
Raltitrexed drug monograph, Ontario Health (Cancer Care Ontario).
Van Meerbeeck J Gaafar R,, Manegold C, et al. Randomized Phase III study of cisplatin with or without Raltitrexed in patients with MPM: An Intergroup study of the European Organization for Research and Treatment of Cancer Lung Cancer Group and the National Cancer Institute of Canada. J Clin Oncol 2005;23:6881-9.
June 2024 Modified Dose Modifications, Interactions, Drug Administration and Special Precautions, and Monitoring sections
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.