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CISPPEME

Cancer Type: Lung, Non-Small Cell  Intent: Adjuvant
Regimen Category: Evidence-Informed
Funding:
New Drug Funding Program
    Pemetrexed - Adjuvant Treatment of Completely Resected Stage II or IIIA Non-Small Cell Lung Cancer
A - Regimen Name

CISPPEME Regimen
CISplatin-Pemetrexed


Disease Site
Lung - Non-Small Cell

Intent
Adjuvant

Regimen Category
Evidence-Informed :

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.


Rationale and Uses

For the treatment of completely resected stage II or IIIA non-small cell lung cancer with non-squamous histology. 


Supplementary Public Funding

pemetrexed
New Drug Funding Program (Pemetrexed - Adjuvant Treatment of Completely Resected Stage II or IIIA Non-Small Cell Lung Cancer) (NDFP Website ) (interim funding for duration of vinorelbine supply interruption )

 
B - Drug Regimen

pemetrexed
500 mg /m² IV Day 1
CISplatin
75 mg /m² IV over 2 hours; 30 minutes after the end of Pemetrexed Day 1
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C - Cycle Frequency

REPEAT EVERY 21 DAYS

For 4 cycles unless disease progression or unacceptable toxicity occurs

 
D - Premedication and Supportive Measures

Antiemetic Regimen:

High

Other Supportive Care:

Pemetrexed:

  • 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 (refer to pemetrexed monograph)

Cisplatin:

  • Standard regimens for Cisplatin premedication and hydration should be followed. Refer to cisplatin monograph and local guidelines.

Also refer to CCO Antiemetic Recommendations.

 
E - Dose Modifications

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

Pemetrexed is not extensively metabolized in the liver. No specific studies have been performed in patients with moderate or severe hepatic impairment. Pemetrexed should be used with caution in patients with hepatic impairment.  Refer to the dose modification table above.
CISplatin:  No adjustment required.

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

 
F - Adverse Effects

Refer to pemetrexed, CISplatin drug monograph(s) for additional details of adverse effects


Most Common Side Effects 

Less Common Side Effects, but may be
Severe or Life-Threatening

  • Nausea, vomiting
  • Myelosuppression ± bleeding, infection (may be severe)
  • Fatigue
  • Diarrhea (may be severe)
  • Mucositis
  • Anorexia
  • Neurotoxicity (including ototoxicity, may be severe)
  • Nephrotoxicity (may be severe)
  • Rash (may be severe)
  • Pneumonitis
  • Arterial thromboembolism
  • Venous thromboembolism
  • Arrhythmia
  • Hemolysis
  • Hypersensitivity
  • GI perforation
  • ↑ LFTs
 
G - Interactions

Refer to pemetrexed, CISplatin drug monograph(s) for additional details

 
 
H - Drug Administration and Special Precautions

Refer to pemetrexed, CISplatin drug monograph(s) for additional details

 
 
I - Recommended Clinical Monitoring

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

  • Clinical toxicity assessment (including neurologic, ototoxicity, fatigue, diarrhea, mucositis, thromboembolism, bleeding, infection, pneumonitis, rash); at each visit
  • CBC before each cycle, including nadir counts
  • Baseline and regular renal function tests (including electrolytes and magnesium) and urinalysis
  • Baseline and regular liver functions tests
  • Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version


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J - Administrative Information

Approximate Patient Visit
4-6 hours
Pharmacy Workload (average time per visit)
41.935 minutes
Nursing Workload (average time per visit)
46.667 minutes
 
K - References

Gauvain C, Crequit P, Rousseau-Bussac G, et al.  Adjuvant chemotherapy of non-small cell lung cancer: Tolerance of combined cisplatin-pemetrexed therapy.  Rev Mal Respir 2014;31(9):817-21. 

Kreuter M, Vansteenkiste J, Fischer JR, et al.  Three-Year Follow-Up of a Randomized Phase II Trial on Refinement of Early-Stage NSCLC Adjuvant Chemotherapy with Cisplatin and Pemetrexed versus Cisplatin and Vinorelbine (the TREAT Study).   J Thorac Oncol 2016;11(1):85-93.


May 2019 added PEBC and antiemetic guideline links


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M - Disclaimer

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.
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