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.
TRIFTIPI
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 the treatment of adult patients with metastatic colorectal cancer who have been previously treated with, or are not candidates for, fluoropyrimidine-based chemotherapy, oxaliplatin, irinotecan, anti-VEGF therapy, and, if RAS wild-type, anti-EGFR therapy.
| trifluridine / tipiracil | 35* mg /m² | PO | BID on Days 1 to 5 and 8 to 12 |
| (This drug is not currently publicly funded for this regimen and intent) | |||
*Based on the trifluridine component; up to a maximum of 80 mg per dose.
Low – No routine prophylaxis; PRN recommended
Other Supportive Care:
Also refer to CCO Antiemetic Recommendations.
Doses should be modified according to the protocol by which the patient is being treated.
Do not start treatment with trifluridine / tipiracil until ANC ≥ 1.5 x 109/L, platelets ≥ 75 x 109/L and non-hematological toxicities ≤ grade 1.
Dosage with toxicity
|
Dose Level |
Dose* (mg/m2) BID |
|
0 |
35 |
|
-1 |
30 |
|
-2 |
25 |
|
-3 |
20 |
| -4 | Discontinue |
*Based on trifluridine component
Dose Calculation Based on Body Surface Area (BSA)
|
Dose |
BSA (m2) |
Dose (mg)* |
Number of tablets per dose |
Total daily dose (mg)* |
|
|
15 mg** |
20 mg** |
||||
|
35 mg/m2 |
< 1.07 |
35 |
1 |
1 |
70 |
|
1.07 – 1.22 |
40 |
0 |
2 |
80 |
|
|
1.23 – 1.37 |
45 |
3 |
0 |
90 |
|
|
1.38 – 1.52 |
50 |
2 |
1 |
100 |
|
|
1.53 – 1.68 |
55 |
1 |
2 |
110 |
|
|
1.69 – 1.83 |
60 |
0 |
3 |
120 |
|
|
1.84 – 1.98 |
65 |
3 |
1 |
130 |
|
|
1.99 – 2.14 |
70 |
2 |
2 |
140 |
|
|
2.15 – 2.29 |
75 |
1 |
3 |
150 |
|
|
≥ 2.3 |
80 |
0 |
4 |
160 |
|
*Given twice daily
**Based on trifluridine component
|
Dose Level |
BSA (m2) |
Dose (mg)* |
Number of tablets per dose |
Total Daily Dose (mg)* |
|
|
15 mg** |
20 mg** |
||||
|
-1 |
< 1.09 |
30 |
2 |
0 |
60 |
|
1.09 – 1.24 |
35 |
1 |
1 |
70 |
|
|
1.25 – 1.39 |
40 |
0 |
2 |
80 |
|
|
1.4 – 1.54 |
45 |
3 |
0 |
90 |
|
|
1.55 – 1.69 |
50 |
2 |
1 |
100 |
|
|
1.7 – 1.94 |
55 |
1 |
2 |
110 |
|
|
1.95 – 2.09 |
60 |
0 |
3 |
120 |
|
|
2.1 – 2.28 |
65 |
3 |
1 |
130 |
|
|
≥ 2.29 |
70 |
2 |
2 |
140 |
|
|
-2 |
<1.1 |
25*** |
2*** |
1*** |
50*** |
|
1.1 – 1.29 |
30 |
2 |
0 |
60 |
|
|
1.3 – 1.49 |
35 |
1 |
1 |
70 |
|
|
1.5 – 1.69 |
40 |
0 |
2 |
80 |
|
|
1.7 – 1.89 |
45 |
3 |
0 |
90 |
|
|
1.9 – 2.09 |
50 |
2 |
1 |
100 |
|
|
2.1 – 2.29 |
55 |
1 |
2 |
110 |
|
|
≥ 2.3 |
60 |
0 |
3 |
120 |
|
|
-3 |
<1.14 |
20 |
0 |
1 |
40 |
|
1.14 – 1.34 |
25*** |
2*** |
1*** |
50*** |
|
|
1.35 – 1.59 |
30 |
2 |
0 |
60 |
|
|
1.6 – 1.94 |
35 |
1 |
1 |
70 |
|
|
1.95 – 2.09 |
40 |
0 |
2 |
80 |
|
|
2.1 – 2.34 |
45 |
3 |
0 |
90 |
|
|
≥ 2.35 |
50 |
2 |
1 |
100 |
|
*Given twice daily
**Based on trifluridine component
***For total daily dose of 50 mg; patients should take 1 x 20 mg tablet in the morning and 2 x 15 mg tablets in the evening.
Dose Modifications:
|
Toxicity |
Action |
|
Hematologic |
|
|
Grade 3 thrombocytopenia (platelets 25 to < 50 x 109/L) |
Hold*; restart next cycle at same dose level |
|
Grade 4 thrombocytopenia or neutropenia (platelets < 25 x 109/L or ANC < 0.5 x 109/L) requiring a > 1 week delay in start of next cycle |
Hold*; restart next cycle at ↓ one dose level |
|
Febrile neutropenia |
Hold*; restart next cycle at ↓ one dose level |
|
Non-hematologic |
|
|
Grade 3 or 4 non-hematologic; except for Grade 3 nausea and/or vomiting controlled by antiemetic therapy or diarrhea responding to antidiarrheal therapy |
Hold*; restart next cycle at ↓ one dose level |
|
Interstitial Lung Disease/Pneumonitis (treatment-related) |
Hold and investigate. If confirmed, discontinue permanently |
|
*Restart when platelets recovered to ≥ 75 x 109/L and ANC recovered to ≥ 1.5 x 109/L and non-hematological toxicities ≤ grade 1. Do not re-escalate dose after it has been reduced. |
|
Hepatic Impairment
Higher incidence of grade 3 or 4 hyperbilirubinemia was observed in patients with moderate hepatic impairment.
|
Hepatic Impairment |
Bilirubin |
|
AST |
Starting Dose |
|
Mild |
≤ ULN |
and |
> ULN |
No adjustment required |
|
< 1 – 1.5 x ULN |
and |
Any |
||
|
Moderate |
> 1.5 – 3 x ULN |
and |
Any |
Not recommended for use |
|
Severe |
> 3 x ULN |
Renal Impairment
Patients with moderate renal impairment (creatinine clearance = 30 - 59 mL/min) had a higher incidence (difference of at least 5%) of ≥ grade 3 adverse events (hemoglobin and leukocytes decreases) and serious adverse events compared to patients with normal or mild renal impairment.
|
Creatinine Clearance (mL/min) |
Starting Dose |
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|
≥ 60 |
No adjustment required |
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|
30 - 59 |
No adjustment required; monitor closely for hematological toxicity and dose adjust accordingly |
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|
15 - 29 |
*Based on the trifluridine component
|
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|
< 15 (End Stage Renal Disease) |
Not studied, no data available |
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Dosage in the Elderly
No adjustments of starting dose needed. No overall differences in effectiveness were reported based on age (≥65 years of age versus <65 years); higher incidences of severe myelosuppression were observed in patients aged ≥ 65 compared with those < 65. Efficacy and safety data in patients ≥ 75 years old is limited.
Dosage based on ethnicity description
No dose adjustments required. Severe, life-threatening, or fatal interstitial lung disease (ILD)/pneumonitis have been rarely observed in one clinical trial of Asian patients as well as post marketing. There is limited data in African American patients.
Refer to trifluridine / tipiracil drug monograph(s) for additional details of adverse effects.
|
Very common (≥ 50%) |
Common (25-49%) |
Uncommon (< 10%), but may be severe or life-threatening |
|
|
|
Refer to trifluridine / tipiracil drug monograph(s) for additional details.
- Monitor for decreased efficacy of human thymidine kinase substrates (e.g. zidovudine), consider switching to alternative antiviral that is not a human thymidine kinase substrate (e.g. lamivudine, abacavir, etc).
Refer to trifluridine / tipiracil drug monograph(s) for additional details.
Administration
-
Trifluridine / tipiracil should be given orally with a glass of water, within one hour of completion of morning and evening meals.
-
If a dose is missed or held, the patient should not make up for the missed dose.
-
Store at room temperature (15 - 30°C) in its original packaging.
Contraindications
-
Patients who have a known hypersensitivity to the drug or to any of its excipients
Warnings/Precautions
-
Contains lactose; carefully consider use in patients with hereditary lactase, glucose or galactose disorders.
-
Use with caution in patients who received prior radiotherapy; may be at higher risk of hematological adverse effects.
Pregnancy/Lactation
-
Trifluridine / tipiracil is not recommended for use in pregnancy. Adequate contraception should be used by both sexes during treatment, and for at least 6 months after the last dose. Women using a hormonal contraceptive must also use a barrier contraceptive, as it is unknown whether trifluridine/tipiracil may reduce the effectiveness of hormonal contraceptives.
-
Breastfeeding is not recommended during treatment and for 1 day after the last dose.
-
Fertility effects: Unlikely
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, before each cycle and at each visit (including Day 15)
Renal function tests; Baseline and at each visitLiver function tests; Baseline and at each visit
Proteinuria (by dipstick); Baseline and as clinically indicated
Clinical toxicity assessment for infection, bleeding, venous thromboembolism, GI and respiratory effects; At each visit
-
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
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Trifluridine / tipiracil drug monograph, Ontario Health (Cancer Care Ontario).
Mayer RJ et al. Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N Engl J Med 2015;372:1909-19.
September 2021 Expanded into full regimen monograph.
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.