Mukherjee, S., Qi, C., Shaw, R. et al. (20 more authors) (2024) Standard or high dose chemoradiotherapy, with or without the protease inhibitor nelfinavir, in patients with locally advanced pancreatic cancer: The phase 1/randomised phase 2 SCALOP-2 trial. European Journal of Cancer, 209. 114236. ISSN 0959-8049
Abstract
Background 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.
Methods 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).
Results 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.
Conclusions 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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies. This is an author produced version of an article published in European Journal of Cancer made available under the CC-BY-NC-ND 4.0 license (http://creativecommons.org/licenses/by-nc-nd/4.0) in accordance with the publisher's self-archiving policy. |
Keywords: | 32 Biomedical and Clinical Sciences; 3202 Clinical Sciences; 3211 Oncology and Carcinogenesis; Cancer; Orphan Drug; Pancreatic Cancer; Digestive Diseases; Clinical Trials and Supportive Activities; Minority Health; Health Disparities; Rare Diseases; Clinical Research; 6.1 Pharmaceuticals; 6.5 Radiotherapy and other non-invasive therapies; 6.2 Cellular and gene therapies; Cancer |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Medical Research (LIMR) > Division of Oncology |
Depositing User: | Symplectic Publications |
Date Deposited: | 16 Aug 2024 10:09 |
Last Modified: | 16 Aug 2024 10:30 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.ejca.2024.114236 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:216164 |
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