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SHR Neuro Cancer Cardio Lipid Metab Microb

Wilson, JM; Fokas, E; Dutton, SJ; Patel, N; Hawkins, MA; Eccles, C; Chu, KY; Durrant, L; Abraham, AG; Partridge, M; Woodward, M; O'Neill, E; Maughan, T; McKenna, WG; Mukherjee, S; Brunner, TB.
ARCII: A phase II trial of the HIV protease inhibitor Nelfinavir in combination with chemoradiation for locally advanced inoperable pancreatic cancer.
Radiother Oncol. 2016; 119(2):306-11 Doi: 10.1016/j.radonc.2016.03.021 [OPEN ACCESS]
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Co-authors Med Uni Graz: Brunner Thomas Baptist
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Abstract:: BACKGROUND AND PURPOSE: Nelfinavir can enhance intrinsic radiosensitivity, reduce hypoxia and improve vascularity. We conducted a phase II trial combining nelfinavir with chemoradiotherapy (CRT) for locally advanced inoperable pancreatic cancer (LAPC). MATERIALS AND METHODS: Radiotherapy (50.4Gy/28 fractions; boost to 59.4Gy/33 fractions) was administered with weekly gemcitabine and cisplatin. Nelfinavir started 3-10days before and was continued during CRT. The primary end-point was 1-year overall survival (OS). Secondary end-points included histological downstaging, radiological response, 1-year progression free survival (PFS), overall survival (OS) and treatment toxicity. An imaging sub-study (n=6) evaluated hypoxia ((18)F-Fluoromisonidazole-PET) and perfusion (perfusion CT) during induction nelfinavir. RESULTS: The study closed after recruiting 23 patients, due to non-availability of Nelfinavir in Europe. The 1-year OS was 73.4% (90% CI: 54.5-85.5%) and median OS was 17.4months (90% CI: 12.8-18.8). The 1-year PFS was 21.8% (90% CI: 8.9-38.3%) and median PFS was 5.5months (90% CI: 4.1-8.3). All patients experienced Grade 3/4 toxicity, but many were asymptomatic laboratory abnormalities. Four of 6 patients on the imaging sub-study demonstrated reduced hypoxia and increased perfusion post-nelfinavir. CONCLUSIONS: CRT combined with nelfinavir showed acceptable toxicity and promising survival in pancreatic cancer.
Find related publications in this database (using NLM MeSH Indexing): Chemoradiotherapy - methods; Combined Modality Therapy - administration & dosage; Disease-Free Survival - administration & dosage; Female - administration & dosage; HIV Protease Inhibitors - therapeutic use; Humans - administration & dosage; Male - administration & dosage; Middle Aged - administration & dosage; Nelfinavir - therapeutic use; Pancreatic Neoplasms - pathology, therapy
Find related publications in this database (Keywords): Nelfinavir; Trial; Pancreatic cancer; Hypoxia; Imaging; Radiosensitisation