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Chemotherapy and other systemic treatment regimens may change due to COVID-19. Find out more at Systemic Treatment Regimens During COVID-19.

A - Regimen Name

TRIFTIPI Regimen
Trifluridine/tipiracil


Disease Site
Gastrointestinal - Colorectal
Gastrointestinal - Gastric / Stomach

Intent
Palliative

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 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.
  • For the treatment of patients with advanced gastric cancer who have received at least 2 previous lines of therapy. 
 
B - Drug Regimen

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

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C - Cycle Frequency

REPEAT EVERY 28 DAYS

Until disease progression or unacceptable toxicity

 
D - Premedication and Supportive Measures

Antiemetic Regimen:

Low – No routine prophylaxis; PRN recommended

Other Supportive Care:

Also refer to CCO Antiemetic Recommendations.

 
E - Dose Modifications

Doses should be modified according to the protocol by which the patient is being treated. The following recommendations have been adapted from the product monograph.

Dosage with toxicity

 Do not start treatment with trifluridine and tipiracil until ANC ≥ 1.5 x 109/L and platelets are ≥ 75 x 109/L and non-hematological toxicities ≤ Grade 1.

Dose Levels:

Dose Level

Dose (mg/m2)

BID

0

35

-1

30

-2

25

-3

20

-4 Discontinue

 

 

Dose Calculation Based on Body Surface Area (BSA)

Dose

BSA (m2)

Dose (mg)*

Number of tablets per dose

Total daily dose (mg)

15mg**

20mg**

35mg/ 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

 

Dose Level

BSA (m2)

Dose (mg)*

Number of tablets per dose

Total daily dose (mg)

15mg**

20mg**

-1
30mg/m
2

< 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
25mg/m
2

<1.1

25a

2a

1a

50a

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
20mg/m
2

<1.14

20

0

1

40

1.14 – 1.34

25a

2a

1a

50a

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

a A total daily dose of 50mg should be taken as 1x 20mg tablet in the morning and 2 x 15mg tablet in the evening.

*given twice daily

**trifluridine component

 

Dose Modifications:

Toxicity

Action within cycle

Action at next cycle

Hematologic

 

 

Grade 3 thrombocytopenia

(platelets < 50 x 109/L) or Grade 4 neutropenia (ANC < 0.5 x 109/L) (requiring ≤ 1 week delay in start of next cycle)

Hold. If recovers prior to Day 8, may restart* at same dose level within cycle (or restart at next cycle)

Restart* at same dose level. If recovers prior to Day 8, may restart in that cycle, or restart at next cycle.

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 N/A

 

* Restart when platelets recovered to ≥ 75 x 109/L and ANC recovered to ≥ 1.5 x 109/L and other toxicities to ≤ 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

Creatinine Clearance

Starting Dose

≥ 60 mL/min

No adjustment required

30 – 59 mL/min

No adjustment required; monitor closely for hematological toxicity and dose adjust accordingly

< 30 mL/min or end stage renal disease

No data available; not recommended for use


Dosage in the Elderly

No adjustments of starting dose needed. No clinically relevant effects of age on effectiveness; 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.

 


 
F - Adverse Effects

Refer to trifluridine / tipiracil drug monograph(s) for additional details of adverse effects


Common (25-49%)

Less common (10-24%)

Uncommon (< 10%),

but may be severe or life-threatening

  • Nausea, vomiting (may be severe)
  • ↓ appetite
  • Fatigue
  • Diarrhea
  • Myelosuppression (may be severe)
  • Fever
  • Venous thromboembolism
  • Pneumonitis
 
H - Drug Administration and Special Precautions

Refer to trifluridine / tipiracil drug monograph(s) for additional details


Administration
 

  • Trifluridine and 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 and 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 one day followng the final dose.

    • Fertility effects: Unlikely

 

 

 
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

  • CBC; Baseline and at each visit (including Day 15)

    Renal function tests; Baseline and at each visit

    Liver function tests; Baseline and at each visit

    Clinical toxicity assessment for bleeding, infection, GI and respiratory symptoms ; At each visit

    Proteinuria (by dipstick); Baseline and as clinically indicated

  • Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version


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K - References

Trifluridine / tipiracil drug monograph, 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.

Shitara K, Doi T, Dvorkin M, et al. Trifluridine/tipiricil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2018;19:1437-48.

 

March 2020 Added gastric cancer as an ST-QBP approved indication.


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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.
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.