Abstract：
BACKGROUND: 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.
OBJECTIVE: 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).
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
OBJECTIVE: 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).
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：大剂量顺铂放化疗（HD-Cis：100mg/m2q3w，三个周期）是局部晚期头颈部鳞状细胞癌（LA-HNSCC）的标准治疗（SOC）。顺铂的累积递送剂量是生存的预后，甚至超过200毫克/平方米，但高毒性损害其递送。
目的：顺铂分馏可能允许，通过降低峰值血清浓度，减少毒性。迄今为止,没有直接比较HD-Cis与分级高剂量顺铂(FHD-Cis).
方法：这是一项多机构随机II期试验，根据术后或确定性放化疗分层，比较LA-HNSCC患者的HD-Cis与FHD-Cis（25mg/m2/dd1-4q3w，共3个周期）。主要终点是累积递送的顺铂剂量。
结果：在2015年12月至2018年4月之间，对124例患者进行了随机分组。FHD-Cis臂的顺铂累积递送剂量中位数为291mg/m2(IQR:251;298),HD-Cis臂为274mg/m2(IQR:198;295)(P=0.054)。接受第三周期顺铂治疗的患者比例较高，与HD-Cis臂相比，FHD-Cis臂中3-4级急性AE的比例较低：81%64%（P=0.04）和10%vs.17%(P=0.002)，分别。中位随访时间为48个月(IQR：41;55)，局部故障率，两个臂之间的PFS和OS相似。
结论：尽管未达到主要终点，FHD-Cis允许更多周期的顺铂以更低的毒性递送，与SOC相比。FHD-Cis与RT同时是一种值得进一步考虑的治疗选择。
目的：顺铂分馏可能允许，通过降低峰值血清浓度，减少毒性。迄今为止,没有直接比较HD-Cis与分级高剂量顺铂(FHD-Cis).
方法：这是一项多机构随机II期试验，根据术后或确定性放化疗分层，比较LA-HNSCC患者的HD-Cis与FHD-Cis（25mg/m2/dd1-4q3w，共3个周期）。主要终点是累积递送的顺铂剂量。
结果：在2015年12月至2018年4月之间，对124例患者进行了随机分组。FHD-Cis臂的顺铂累积递送剂量中位数为291mg/m2(IQR:251;298),HD-Cis臂为274mg/m2(IQR:198;295)(P=0.054)。接受第三周期顺铂治疗的患者比例较高，与HD-Cis臂相比，FHD-Cis臂中3-4级急性AE的比例较低：81%64%（P=0.04）和10%vs.17%(P=0.002)，分别。中位随访时间为48个月(IQR：41;55)，局部故障率，两个臂之间的PFS和OS相似。
结论：尽管未达到主要终点，FHD-Cis允许更多周期的顺铂以更低的毒性递送，与SOC相比。FHD-Cis与RT同时是一种值得进一步考虑的治疗选择。
