P-182 - Clinical outcomes of a phase II study of nelfinavir, a hypoxia-modifying agent, in combination with chemoradiotherapy in locally-advanced pancreatic...

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Anti-Cancer Agents & Biologic Therapy
Pancreatic Cancer
Surgery and/or Radiotherapy of Cancer
Presenter J. Wilson
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors J. Wilson1, S. Hackett2, L. Durrant1, S. Dutton1, K.-. Chu1, C. Eccles1, A. Abraham1, E. O'Neill1, M. Partridge1, M. Hawkins1, W. McKenna1, T. Maughan3, T. Brunner4, S. Mukherjee1
  • 1University of Oxford, Oxford/UK
  • 2UMC Utrecht, Utrecht/NL
  • 3Gray Institute of Radiation Oncology and Biology, Oxford/UK
  • 4University Hospitals Freiburg, Freiburg im Breisgau/DE



The additional benefit of chemoradiotherapy (CRT) over chemotherapy in locally-advanced pancreatic cancer (LAPC) is uncertain. Optimising local therapy for a subset that never develops distant disease may prolong survival. The prognostic role of sequential FDG-PET in CRT for LAPC warrants further investigation. Nelfinavir is thought to enhance radiosensitivity through hypoxia reduction by increasing tumour blood flow but this had not yet been shown in human tumours.


A non-randomised, single centre phase II study, in FDG-PET-selected patients with histologically proven LAPC. CRT consisted of: nelfinavir 1250 mg bd (days -3 to 45); gemcitabine 300 mg/m2 & cisplatin 30 mg/m2 (days 2, 9, 23 & 30); concurrent radiotherapy: 59.4 Gy/33# to primary tumour, 50.4 Gy/28# to regional nodes. FDG-PET was performed before and 6 weeks after completing CRT. Adjuvant gemcitabine was given for 6 months. Primary endpoint: 1 year overall survival (OS); secondary endpoints included: toxicity, response rate, resectability, median progression free survival (PFS), OS and local PFS. 6 patients had sequential dynamic 18fluoromisonidazole PET (FMISO-PET) and perfusion CT (pCT) before and after 6-7 days of nelfinavir (given from day -8).


23 patients entered between Feb 2010-July2014. The trial was stopped because of unavailability of nelfinavir in Europe. 3 patients did not complete treatment (1 each of PE, biliary sepsis, stroke). Common G3/4 toxicities: thrombocytopenia/leukopenia (both 35%), diarrhoea (17%), nausea/vomiting (17%), fatigue (13%). 1 year and median OS: 76.7% (95% CI 52.8-89.6) and 17.4 months (95% CI 12.7-22.8) respectively. 1 year PFS and Local PFS: 36.8% (16.5-57.5) and 52.9% (95% CI 25.2-74.4) respectively. 2 patients became resectable. Median FDG SUVmax pre- and post-CRT was 7.6 (range 2.6-15.6) and 3.8 (1.6-7.9) respectively (p = 0.002). The median change (%Δ) in FDG SUVmax was -44.2%. Single time point SUVmax did not offer any prognostic information, but%ΔSUVmax did. Patients with%Δ SUVmax > median had a median OS of 23.0 months compared to 14.6 months with%Δ SUVmax < median (p = 0.01). 4/6 patients had reduced FMISO retention and increased pCT derived blood flow post-nelfinavir. Mean change in FMISO-k3 (2 tissue compartmental model) -50.3% vs 6% and blood flow 20.1 vs -7.1% in responders vs non-responders. 8/13 demonstrated a reduction in pAKT in peripheral blood mononuclear cells.


Nelfinavir with CRT is well tolerated with promising outcomes, as these patients were not pre-selected through induction chemotherapy. Change in FDG-PET SUVmax offers prognostic information. Modulation of hypoxia and blood flow by nelfinavir was demonstrated. A randomised phase II study, SCALOP2, opens in 2015.