• Indicated only for heavily pre-treated metastatic colorectal cancer
• Significant myelosuppression risk (neutropenia, thrombocytopenia) – FBC required before each cycle
• Bevacizumab risks: GI perforation, haemorrhage, thromboembolism, hypertension, proteinuria, impaired wound healing
• Do not use if CrCl < 15 mL/min – trifluridine/tipiracil not studied in end-stage renal disease
• Avoid live vaccines during treatment
• Hold bevacizumab around surgery – stop ≥ 6 weeks before elective surgery, restart ≥ 28 days after if wound healed
• Any fever, abdominal pain, bleeding, neurological symptoms, or severe hypertension requires urgent assessment
Generic name: Trifluridine/Tipiracil + Bevacizumab
Brand name: Lonsurf (trifluridine/tipiracil) + bevacizumab
Drug class:
• Trifluridine/Tipiracil – Antimetabolite (nucleoside analogue)
• Bevacizumab – Anti-VEGF monoclonal antibody
Formulation:
• Trifluridine/Tipiracil – Oral tablets
• Bevacizumab – IV infusion
Mechanism of action:
• Trifluridine incorporates into DNA causing tumour cell death; tipiracil inhibits degradation of trifluridine
• Bevacizumab inhibits VEGF-A, reducing tumour angiogenesis
Metastatic colorectal cancer (CRC) in adult patients who:
• Have been previously treated with, or
• Are not considered candidates for, the following therapies:
– Fluoropyrimidine-based chemotherapy
– Oxaliplatin-based chemotherapy
– Irinotecan-based chemotherapy
– Anti-VEGF therapy
– Anti-EGFR therapy (if RAS wild-type)
Additional requirements:
• ECOG performance status 0–1 only
Cycle length: 28 days
Trifluridine/Tipiracil:
• 35 mg/m² twice daily (based on trifluridine component)
• Maximum dose cap: 80 mg per dose
• Oral administration on Days 1–5 and Days 8–12
• Take within 1 hour after a meal
• Swallow tablets whole – do not crush or chew
Bevacizumab:
• 5 mg/kg IV infusion on Days 1 and 15
Treatment continues until disease progression or unacceptable toxicity.
Haematological toxicity:
• Delay treatment if ANC < 1.0 × 10⁹/L or platelets < 75 × 10⁹/L
• Reduce trifluridine/tipiracil dose by 5 mg/m² for subsequent cycles after significant neutropenia, thrombocytopenia, or febrile neutropenia
Renal impairment:
• CrCl 30–59 mL/min: Use with caution, higher toxicity risk
• CrCl 15–29 mL/min: Reduce starting dose to 20 mg/m² twice daily
• CrCl < 15 mL/min: Not recommended
Hepatic impairment:
• Mild: No dose adjustment
• Moderate or severe: Trifluridine/tipiracil not recommended
Non-haematological toxicity (e.g. diarrhoea, mucositis):
• Delay until resolved to Grade 1 or less
• Stepwise dose reductions; discontinue after repeated severe toxicity
Bevacizumab must be permanently discontinued if:
• GI perforation or fistula
• Grade ≥ 3 haemorrhage
• Arterial thromboembolic event
• RPLS
• Nephrotic syndrome
• Uncontrolled severe hypertension
• Hypersensitivity to trifluridine, tipiracil, or bevacizumab
• Pregnancy or breastfeeding
• End-stage renal disease (CrCl < 15 mL/min)
• Active serious bleeding or recent arterial thromboembolic events
• Uncontrolled hypertension
• FBC, renal function, liver function: Baseline and before each cycle
• Blood pressure: Baseline and during treatment
• Urinalysis for proteinuria: Baseline and periodically
• Monitor closely for infection, bleeding, abdominal pain, neurological symptoms
• Clinical review mid-cycle during first cycle if high risk
Very common and common:
• Neutropenia, thrombocytopenia, anaemia
• Fatigue
• Nausea, vomiting
• Diarrhoea
• Oral mucositis
• Abdominal pain
• Hypertension
• Epistaxis
• Proteinuria
Serious:
• Febrile neutropenia
• Sepsis
• Gastrointestinal perforation
• Major haemorrhage
• Venous or arterial thromboembolism
• Reversible posterior leukoencephalopathy syndrome
• Impaired wound healing
• Live vaccines – contraindicated
• Anticoagulants and antiplatelet agents – increased bleeding risk
• NSAIDs and steroids – increased GI perforation risk with bevacizumab
• Thymidine kinase-dependent antivirals – reduced antiviral efficacy
• Anthracyclines – increased cardiotoxicity with bevacizumab
• Pregnancy: Contraindicated – risk of foetal harm
• Breastfeeding: Contraindicated
• Elderly (>75 years): Use with caution due to higher toxicity
• Renal impairment: Dose adjustments required as above
• Hepatic impairment: Not recommended if moderate to severe
Continue treatment until disease progression or unacceptable toxicity.
Permanently discontinue if:
• Life-threatening haematological toxicity
• GI perforation or fistula
• Severe bleeding or thromboembolic event
• RPLS
• Inability to tolerate treatment despite dose reductions
| Generic Name | Trifluridine/Tipiracil |
|---|---|
| Drug Class | 1 |
| Cost | |
| Company | |
|---|---|
| Drug Rep | Admin |
| Indications | Colon Cancer |
| Dosage |