{Reference Type}: Journal Article
{Title}: Standard versus fractionated high-dose cisplatin plus radiation for locally advanced head and neck cancer: Results of the CisFRad (GORTEC 2015-02) randomized phase II trial.
{Author}: Borel C;Sun XS;Coutte A;Bera G;Sire C;Zanetta S;Alfonsi M;Janoray G;Chatellier T;Garcia-Ramirez M;Gherga E;Hammoud Y;Burgy M;Etienne-Selloum N;Pechery A;Girard-Calais MH;Velten M;Pignon JP;Wanneveich M;Bourhis J;
{Journal}: Radiother Oncol
{Volume}: 197
{Issue}: 0
{Year}: 2024 Aug 19
{Factor}: 6.901
{DOI}: 10.1016/j.radonc.2024.110329
{Abstract}: <B>BACKGROUND: </B>Chemoradiotherapy with high-dose cisplatin (HD-Cis: 100 mg/m2 q3w for three cycles) is the standard of care (SOC) in locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Cumulative delivered dose of cisplatin is prognostic of survival, even beyond 200 mg/m2 but high toxicity compromises its delivery.<BR><B>OBJECTIVE: </B>Cisplatin fractionation may allow, by decreasing the peak serum concentration, to decrease toxicity. To date, no direct comparison was done of HD-Cis versus fractionated high dose cisplatin (FHD-Cis).<BR><B>METHODS: </B>This is a multi-institutional randomized phase II trial, stratified on postoperative or definitive chemoradiotherapy, comparing HD-Cis to FHD-Cis (25 mg/m2/d d1-4 q3w for 3 cycles) in patients with LA-HNSCC. The primary endpoint was the cumulative delivered cisplatin dose.<BR><B>RESULTS: </B>Between December 2015 and April 2018, 124 patients were randomized. Median cisplatin cumulative delivered dose was 291 mg/m2 (IQR: 251;298) in the FHD-Cis arm and 274 mg/m2 (IQR: 198;295) in the HD-Cis arm (P = 0.054). The proportion of patients receiving a third cycle of cisplatin was higher, with a lower proportion of grade 3-4 acute AEs in the FHD-Cis arm compared to the HD-Cis arm: 81 % vs. 64 % (P = 0.04) and 10 % vs. 17 % (P = 0.002), respectively. With a median follow-up of 48 months (IQR: 41;55), locoregional failure rate, PFS and OS were similar between the two arms.<BR><B>CONCLUSIONS: </B>Although the primary endpoint was not met, FHD-Cis allowed more cycles of cisplatin to be delivered with lower toxicity, when compared to SOC. FHD-Cis concurrently with RT is a treatment option which deserves further consideration.