Mukherjee Somnath, Qi Cathy, Shaw Rachel, Jones Christopher M, Bridgewater John A, Radhakrishna Ganesh, Patel Neel, Holmes Jane, Virdee Pradeep S, Tranter Bethan, Parsons Philip, Falk Stephen, Wasan Harpreet S, Ajithkumar Thankamma V, Holyoake Daniel, Roy Rajarshi, Scott-Brown Martin, Hurt Christopher N, O'Neill Eric, Sebag-Montefiore David, Maughan Tim S, Hawkins Maria A, Corrie Pippa
Oxford Cancer Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Centre for Statistics in Medicine, University of Oxford, Oxford, UK.
Eur J Cancer. 2024 Sep;209:114236. doi: 10.1016/j.ejca.2024.114236. Epub 2024 Jul 23.
The multi-centre two-stage SCALOP-2 trial (ISRCTN50083238) assessed whether dose escalation of consolidative chemoradiotherapy (CRT) or concurrent sensitization using the protease inhibitor nelfinavir improve outcomes in locally advanced pancreatic cancer (LAPC) following four cycles of gemcitabine/nab-paclitaxel.
In stage 1, the maximum tolerated dose (MTD) of nelfinavir concurrent with standard-dose CRT (50.4 Gy in 28 fractions) was identified from a cohort of 27 patients. In stage 2, 159 patients were enrolled in an open-label randomized controlled comparison of standard versus high dose (60 Gy in 30 fractions) CRT, with or without nelfinavir at MTD. Primary outcomes following dose escalation and nelfinavir use were respectively overall survival (OS) and progression free survival (PFS). Secondary endpoints included health-related quality of life (HRQoL).
High dose CRT did not improve OS (16.9 (60 % confidence interval, CI 16.2-17.7) vs. 15.6 (60 %CI 14.3-18.2) months; adjusted hazard ratio, HR 1.13 (60 %CI 0.91-1.40; p = 0.68)). Similarly, median PFS was not improved by nelfinavir (10.0 (60 %CI 9.9-10.2) vs. 11.1 (60 %CI 10.3-12.8) months; adjusted HR 1.71 (60 %CI 1.38-2.12; p = 0.98)). Local progression at 12 months was numerically lower with high-dose CRT than with standard dose CRT (n = 11/46 (23.9 %) vs. n = 15/45 (33.3 %)). Neither nelfinavir nor radiotherapy dose escalation impacted on treatment compliance or grade 3/4 adverse event rate. There were no sustained differences in HRQoL scores between treatment groups over 28 weeks post-treatment.
Dose-escalated CRT may improve local tumour control and is well tolerated when used as consolidative treatment in LAPC but does not impact OS. Nelfinavir use does not improve PFS.
多中心两阶段SCALOP-2试验（ISRCTN50083238）评估了在接受四个周期吉西他滨/纳米白蛋白结合型紫杉醇治疗后，巩固性放化疗（CRT）剂量递增或使用蛋白酶抑制剂奈非那韦进行同步增敏是否能改善局部晚期胰腺癌（LAPC）的治疗效果。
在第1阶段，从27例患者队列中确定了奈非那韦与标准剂量CRT（28次分割，总剂量50.4 Gy）同时使用时的最大耐受剂量（MTD）。在第2阶段，159例患者被纳入一项开放标签的随机对照试验，比较标准剂量与高剂量（30次分割，总剂量60 Gy）CRT，以及是否联合使用MTD剂量的奈非那韦。剂量递增和使用奈非那韦后的主要结局分别为总生存期（OS）和无进展生存期（PFS）。次要终点包括健康相关生活质量（HRQoL）。
高剂量CRT未改善OS（16.9个月（60%置信区间，CI 16.2 - 17.7） vs. 15.6个月（60%CI 14.3 - 18.2）；校正风险比，HR 1.13（60%CI 0.91 - 1.40；p = 0.68））。同样，奈非那韦也未改善中位PFS（10.0个月（60%CI 9.9 - 10.2） vs. 11.1个月（60%CI 10.3 - 12.8）；校正HR 1.71（60%CI 1.38 -
