Abstract
Background and purposeNelfinavir 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 methodsRadiotherapy (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 (18F-Fluoromisonidazole-PET) and perfusion (perfusion CT) during induction nelfinavir. ResultsThe 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. ConclusionsCRT combined with nelfinavir showed acceptable toxicity and promising survival in pancreatic cancer.
Highlights
Background and purposeNelfinavir can enhance intrinsic radiosensitivity, reduce hypoxia and improve vascularity
We have previously demonstrated that the anti-retroviral drug Nelfinavir can enhance intrinsic radiosensitivity, reduce hypoxia and improve vascularity, potentially through Akt inhibition [10,11,12]
All patients were staged with FDG PET-computer tomography (CT) and discussed at the pancreatic multidisciplinary meeting (MDM) where specialist pancreatic surgeons, radiologists and oncologists agreed on decision regarding inoperability and suitability for CRT
Summary
Background and purposeNelfinavir can enhance intrinsic radiosensitivity, reduce hypoxia and improve vascularity. Materials and methods: Radiotherapy (50.4 Gy/28 fractions; boost to 59.4 Gy/33 fractions) was administered with weekly gemcitabine and cisplatin. 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 (18F-FluoromisonidazolePET) and perfusion (perfusion CT) during induction nelfinavir. The 1-year OS was 73.4% (90% CI: 54.5–85.5%) and median OS was 17.4 months (90% CI: 12.8–18.8). The 1year PFS was 21.8% (90% CI: 8.9–38.3%) and median PFS was 5.5 months (90% CI: 4.1–8.3). Four of 6 patients on the imaging sub-study demonstrated reduced hypoxia and increased perfusion postnelfinavir. Conclusions: CRT combined with nelfinavir showed acceptable toxicity and promising survival in pancreatic cancer.
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