{Reference Type}: Journal Article
{Title}: Trifluridine/Tipiracil Based Chemoradiation in locally Advanced Rectal Cancer: The Phase I/II TARC Trial.
{Author}: Thiele B;Stein A;Schultheiß C;Paschold L;Jonas H;Goekkurt E;Rüssel J;Schuch G;Wierecky J;Sinn M;Tintelnot J;Petersen C;Rothkamm K;Vettorazzi E;Binder M;
{Journal}: Clin Colorectal Cancer
{Volume}: 0
{Issue}: 0
{Year}: 2024 Jun 22
{Factor}: 4.035
{DOI}: 10.1016/j.clcc.2024.06.003
{Abstract}: <B>BACKGROUND: </B>Optimizing functional outcomes and securing long-term remissions are key goals in managing patients with locally advanced rectal cancer. In this proof-of-concept study, we set out to further optimize neoadjuvant therapy by integrating the radiosensitizer trifluridine/tipiracil and explore the potential of cell free tumor DNA (ctDNA) to monitor residual disease.<BR><B>METHODS: </B>About 10 patients were enrolled in the phase I dose finding part which followed a 3 + 3 dose escalation design. Tipiracil/trifluridine was administered concomitantly to radiotherapy. ctDNA monitoring was performed before and after chemoradiation with patient-individualized digital droplet PCRs.<BR><B>RESULTS: </B>No dose-limiting toxicities were observed at the maximum tolerated dose level of 2 × 35 mg/m² trifluridine/tipiracil. There were 9 grade 3 adverse events, of which 8 were hematologic with anemia and leukopenia. Chemoradiation yielded a pathological complete response in 1 out of 8 assessable patients, downstaging in nearly all patients, and 1 clinical complete response referred for watchful waiting. Three of 4 assessable patients with residual tumor cells at pathological assessment remained liquid biopsy positive after chemoradiation, but 1 turned negative.<BR><B>CONCLUSIONS: </B>In this exploratory phase I trial, the novel combination of neoadjuvant trifluridine/tipiracil and radiotherapy proved to be feasible, tolerable, and effective. However, the application of liquid biopsy as a potential marker for therapeutic de-escalation in the neoadjuvant setting requires additional research and prospective validation. The trial was registered at ClinicalTrials.gov: NCT04177602.