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

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.