Lonsurf® received Pharmaceutical Benefits Scheme (PBS) listing on 1st December 2018 for the treatment of metastatic colorectal cancer in adult patients who have been treated previously with or are not candidates for currently available therapies.
Lonsurf® is a combination of a cytotoxic active thymidine-based nucleic acid analogue, trifluridine, and a thymidine phosphorylase inhibitor, tipiracil hydrochloride. The cytotoxic tri-phosphate form of trifluridine is incorporated into DNA which appears to result in anti-tumour activity. Tipiracil hydrochloride is a potent inhibitor of thymidine phosphorylase, which prevents rapid degradation of trifluridine and in turn allows for the maintenance of adequate plasma levels of the active drug.
Over 17,000 Australians are predicted to be diagnosed with colorectal cancer in 2018, and this is the second leading cause of cancer death in Australia. There is a high survival rate if colorectal cancer is diagnosed early. However, those with metastatic disease have a dismal outlook.
The efficacy of Lonsurf® was investigated in the RECOURSE trial, where treatment with Lonsurf® with best supportive care (BSC) demonstrated a clinically meaningful and statistically significant benefit in comparison to placebo with BSC. A disease response rate of 44% was demonstrated, with a median overall survival rate of 7.2 months and a 1-year survival Kaplan-Meier estimate of 27.1%.
Lonsurf® is administered orally twice daily on Days 1 to 5 and Days 8 to 12 over a 28-day cycle, repeating as long as benefit is observed or until unacceptable toxicity. It is to be taken within an hour after breakfast and dinner, and a common counselling point would suggest ‘Monday to Friday twice a day, within an hour of breakfast and dinner, on weeks 1 and 2 of the treatment cycle and two weeks off’. A dosing calendar from Servier can be provided to patients to aid dosing compliance.
The recommended starting dose is 35mg/m² (based on the trifluridine component), and a maximum of three dose reductions to a minimum dose of 20mg/m² is permitted. Dose escalation after a reduction is not allowed.
The most serious observed adverse effects were bone marrow suppression and gastrointestinal toxicities, with the most common grade 3/4 adverse effects reported included neutropenia, anaemia, leucopenia, diarrhoea and fatigue. In the RECOURSE trial, 53% of patients treated with Lonsurf® for two or more cycles required a dose delay of ≥4 days due to toxicity, 14% of patients required dose reductions and 4% withdrew due to adverse effects.
- Mayer RJ, Cutsem EV, Falcone A, Yoshino T, Garcia-Carbonero R, Mizunuma N, et al. Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N Engl J Med. 2015; 372: 1909-19.
- Lonsurf® (Trifluridine / Tipiracil) Australian approved product information. Hawthorn: Servier. Approved August 2018.