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

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 (50.4 Gy/28 fractions; boost to 59.4 Gy/33 fractions) was administered with weekly gemcitabine and cisplatin. Nelfinavir started 3–10 days 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 17.4 months (90% CI: 12.8–18.8). The 1-year PFS was 21.8% (90% CI: 8.9–38.3%) and median PFS was 5.5 months (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.

Nonmetastatic pancreatic cancer

“…In LAPC patients the mOS in the present analysis was roughly 20 months, which seems to be superior to the mOS rates reported in the majority of clinical trials (8.3–17.4 months; [9–12, 41–43]). Being aware of the fact that a comparison with prospectively collected data is indirect (supplementary Table 2) a critical discussion of our findings has to consider patient selection as well as therapy regimens and toxicity.…”

Dosimetric parameters correlate with duodenal histopathologic damage after stereotactic body radiotherapy for pancreatic cancer: Secondary analysis of a prospective clinical trial

“…It is important to note that previous dosimetric studies, which have also been less than consistent in terms of most reliable dosimetric parameters, have either studied dosimetry of SBRT alone or concurrent chemoradiotherapy; it is possible that sequential chemotherapy and SBRT could have differing dosimetric profiles due to full-course, dual-agent chemotherapy having been received prior to SBRT in this series. The addition of nelfinavir also cannot be discounted, and a complete account of clinical toxicities (especially in similar settings) has not been described aside from two reports [30–31]. However, nelfinavir has no known data associated with radioprotection; though any of the gastrointestinal side effects observed herein are possible with nelfinavir, they are all quite uncommon [30–31].…”

“…The addition of nelfinavir also cannot be discounted, and a complete account of clinical toxicities (especially in similar settings) has not been described aside from two reports [30–31]. However, nelfinavir has no known data associated with radioprotection; though any of the gastrointestinal side effects observed herein are possible with nelfinavir, they are all quite uncommon [30–31]. Whereas many previous dosimetric studies have been retrospective in nature, a strength of this work is decreasing retrospective biases owing to prospectively collecting these data, having prespecified this secondary analysis when this clinical trial commenced accrual.…”

Can Nigella Sativa and Pure Honey Improved Chemoradiotherapy Effects in Advanced Pancreatic Cancer

“…Biswa Mohan and colleagues made a preliminary study about pure honey for decreasing oral mucosal toxicity. The studies shown that topical pure honey reduces oral mucositis as dramatical [37,38]. The antioxidant, antiproliferative, antimicrobial effects of 3 to 20g of honey demonstrated in multiple studies [38][39][40][41][42][43].…”

“…The studies shown that topical pure honey reduces oral mucositis as dramatical [37,38]. The antioxidant, antiproliferative, antimicrobial effects of 3 to 20g of honey demonstrated in multiple studies [38][39][40][41][42][43]. In Islamic medicine and Iran, the combination of NS with honey is used for alleviating gastrointestinal symptoms like abdominal pain, bloating and diarrhea [44][45][46].…”