ARCII: A phase II trial of the HIV protease inhibitor Nelfinavir in combination with chemoradiation for locally advanced inoperable pancreatic cancer.
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).



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.



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.



CRT combined with nelfinavir showed acceptable toxicity and promising survival in pancreatic cancer.
Department of Oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, UK.
James M
JM
Wilson
Department of Oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, UK.
Emmanouil
E
Fokas
Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, UK.
Susan J
SJ
Dutton
Department of Radiology, Oxford University Hospitals NHS Foundation Trust, UK.
Neel
N
Patel
Department of Oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, UK.
Maria A
MA
Hawkins
Department of Radiotherapy, Oxford University Hospitals NHS Foundation Trust, UK.
Cynthia
C
Eccles
Department of Oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, UK; Department of Radiotherapy, Oxford University Hospitals NHS Foundation Trust, UK.
Kwun-Ye
KY
Chu
Department of Radiotherapy, Oxford University Hospitals NHS Foundation Trust, UK.
Lisa
L
Durrant
Department of Oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, UK.
Aswin G
AG
Abraham
Department of Oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, UK.
Mike
M
Partridge
Early Phase Research Hub, Department of Oncology, Oxford Cancer and Haematology Centre, Oxford University Hospitals NHS Foundation Trust, UK.
Martha
M
Woodward
Department of Oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, UK.
Eric
E
O'Neill
Department of Oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, UK.
Tim
T
Maughan
Department of Oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, UK.
W Gillies
WG
McKenna
Department of Oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, UK. Electronic address: somnath.mukherjee@oncology.ox.ac.uk.
Somnath
S
Mukherjee
Department of Radiation Oncology, University of Freiburg, Germany; German Cancer Consortium (DKTK), Heidelberg, Partner Site Freiburg, Germany.
Thomas B
TB
Brunner
D059248:Chemoradiotherapy / Q000379:methods*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019888:Nelfinavir / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000628:therapy*
D017320:HIV Protease Inhibitors; D019888:Nelfinavir
Hypoxia; Imaging; Nelfinavir; Pancreatic cancer; Radiosensitisation; Trial