Drug Formulary information is intended for use by healthcare professionals. It is not intended to be medical advice. Some of the information, including information about funding for cancer drugs, does not apply to all patients. Cancer treatment plans are unique to each patient. If you are a patient, please speak with your healthcare team to understand how this information applies to you.
CISPPEME
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 patients with malignant peritoneal mesothelioma that is not amenable to curative treatment with surgery
| pemetrexed | 500 mg /m² | IV in 100 mL NS over 10 minutes | Day 1 |
| CISplatin | 75 mg /m² | IV over 2 hours; 30 minutes after the end of Pemetrexed | Day 1 |
REPEAT EVERY 21 DAYS
Until disease progression or unacceptable toxicity, usually up to 6 cycles due to cumulative cisplatin toxicity
High
Other Supportive Care:
Also refer to CCO Antiemetic Summary
- Standard regimens for Cisplatin premedication and hydration should be followed when used in combination with pemetrexed. Refer to local guidelines.
- Vitamin B12 1000mcg IM every 9 weeks, Folic acid 0.4 - 1 mg PO daily (both starting ≥ 1 week prior to pemetrexed administration; continue throughout and 3 weeks after last dose of Pemetrexed).
- Dexamethasone 4mg PO BID for 3 days starting day before chemotherapy suggested for rash prophylaxis.
- Note: NSAIDs should be held for 2-5 days prior and 2 days after pemetrexed.
Doses should be modified according to the protocol by which the patient is being treated.
Dosage with toxicity
|
Worst toxicity in previous cycle |
Pemetrexed (% previous dose)* |
Cisplatin (% previous dose, if applicable)* |
|
|
Thrombocytopenic bleeding
|
50%
|
50%
|
|
|
Grade 4 ANC or ≥ Grade 3 platelets
|
75%
|
75%
|
|
|
Grade 2 neurotoxicity
|
100%
|
50%
|
|
|
Grade 3 or 4 mucositis
|
50%
|
100%
|
|
|
Diarrhea requiring hospitalization, or grade 3 or 4 |
75%
|
75%
|
|
|
Grade 3 or 4 neurotoxicity
|
Discontinue
|
||
|
Symptoms suggesting pneumonitis
|
Hold and investigate; discontinue if confirmed |
||
|
Other Grade 3 related organ / non-hematologic toxicity |
75%
|
75%
|
|
|
Other Grade 4 related organ / non-hematologic toxicity |
Discontinue
|
||
|
Grade 3 or 4 toxicity after 2 prior dose reductions, any occurrence of Stevens-Johnson syndrome, Toxic epidermal necrolysis |
Discontinue
|
||
|
*Start next cycle only when ANC ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L and related organ/non-hematologic toxicity ≤ grade 2 (or recovery to baseline). |
|||
Hepatic Impairment
Renal Impairment
|
Creatinine clearance (mL/min)
|
Cisplatin (% previous dose) |
Pemetrexed (% previous dose) |
|
61-79
|
100%
|
100%; but use NSAIDs with extreme caution |
|
45-60
|
75%
|
|
|
30-<45
|
50%
|
Discontinue
|
|
<30
|
Discontinue
|
Discontinue
|
Dosage in the Elderly
No dose adjustments are needed but patients should be monitored closely. Myelosuppression, infection, nausea and renal effects are more common in the elderly in combination with cisplatin for NSCLC.
Refer to pemetrexed, 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 pemetrexed, CISplatin drug monograph(s) for additional details
- Nephrotoxic drugs (e.g. aminoglycosides) may increase the toxicity of pemetrexed and exacerbate nephro and ototoxicity with cisplatin; avoid if possible, or caution during or shortly after cisplatin therapy (for 1-2 weeks)
- NSAIDs may increase the toxicity of pemetrexed. Hold NSAIDs with shorter half-lives (e.g. ibuprofen) at least 2 days before to 2 days after pemetrexed. Hold NSAIDs with long half-lives (e.g. piroxicam) 5 days before to 2 days after pemetrexed.
- Phenytoin levels may be altered by cisplatin. Monitor and adjust phenytoin dose as required.
Refer to pemetrexed, CISplatin drug monograph(s) for additional details
Administration
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.
Pemetrexed:
- Reconstitute as directed with Normal Saline.
- Dilute drug in 100mL (Normal Saline only); Infuse IV over 10 minutes.
- Incompatible with calcium-containing solutions.
- Do not co-administer with other drugs and diluents.
- Keep unopened vials at room temperature. Pemetrexed is not light sensitive.
Contraindications
- Patients who have a hypersensitivity to these drugs or other platinum-containing compounds
- Patients who are myelosuppressed
- Patients with moderate-severe renal impairment (CrCl < 45 ml/min)
- Patients with hearing impairment, unless the possible benefits outweigh the risk
- Avoid the use of live vaccines
Other warnings/precautions
- Patients with pre-existing cardiovascular risk factors
Pregnancy & lactation
- This regimen is not recommended 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 not recommended during this treatment and after the last treatment dose. Refer to the drug monograph(s) for recommendations after the last treatment dose (if available).
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
- Liver function tests; baseline and regular
- Renal function tests; baseline and regular, including electrolytes
- Audiogram; baseline and as clinically indicated
- Clinical toxicity assessment for neurotoxicity, ototoxicity, hypersensitivity, bleeding, infection, GI, and pulmonary effects; at each visit
-
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
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Cisplatin and pemetrexed drug monographs, Cancer Care Ontario.
Garcia-Carbonero RG, Paz-Ares L. Systemic chemotherapy in the management of malignant peritoneal mesothelioma. Eur J Surg Oncol 2006;32(6):676-81.
Jänne PA, Wozniak AJ, Belani CP, et al. Open-label study of pemetrexed alone or in combination with cisplatin for the treatment of patients with peritoneal mesothelioma: outcomes of an expanded access program. Clin Lung Cancer. 2005 Jul;7(1):40-6.
August 2023 Modified Pregnancy/lactation 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.