Phase I/II Trial of Sequential Treatment of Nab-Paclitaxel in Combination with Gemcitabine Followed by Modified FOLFOX Chemotherapy in Patients with Untreated Metastatic Exocrine Pancreatic Cancer: Phase I Results.

Background: Although occasioned through different mechanisms, the potential neurotoxicity and also haematological toxicity of nab-paclitaxel and oxaliplatin-based chemotherapy regimen were studied in this trial, which aimed to determine the maximum-tolerated dose (MTD) and to evaluate safety and efficacy of the combination in a sequential regimen of nab-paclitaxel, gemcitabine (GEM) and modified FOLFOX (mFOLFOX) in untreated patients with metastatic pancreatic ductal adenocarcinoma (PDAC). Materials and methods: Treatment consisted of nab-paclitaxel (125/100 mg/m(2)) plus GEM (1000/800 mg/m(2)) on days 1, 8 and 15, followed by mFOLFOX (oxaliplatin [85/75/65 mg/m(2)], 5-FU bolus [400/300/200 mg/m(2)], 5-FU infusion [2400/2000/1600 mg/m(2)]) on day 28, of a 42-day cycle. Patients were enrolled at the highest dose level with a subsequent 3 thorn 3 dose de-escalation plan. Results: Eleven patients (median age = 61, 64% with performance status [PS] = 1) were eligible. All patients received the highest dose level. No de-escalation was needed. A dose-limiting toxicity was reported, an upper gastrointestinal haemorrhage. The MTD was nab-paclitaxel 125 mg/m(2), GEM 1000 mg/m(2), oxaliplatin 85 mg/m(2), 5-FU bolus 400 mg/m(2) and 5-FU infusion 2400 mg/m(2). Common all-grade toxicities were neutropenia (73%), anaemia (55%), thrombocytopenia (55%) and asthenia (55%). Other relevant toxicities were paraesthesia (46%), nausea (36%), dysesthesia (27%) and pyrexia (27%). Objective response rate was 50% and disease control rate was 80%. Conclusions: The regimen of nab-paclitaxel plus GEM followed by mFOLFOX showed favourable safety and tolerability profiles with significant anti-tumor activity. More data are being achieved in a randomised phase II trial, to confirm efficacy rates and dismiss long-term neurotoxicity concerns regarding the sequencing of nab-paclitaxel and oxaliplatin. (C) 2020 Elsevier Ltd. All rights reserved.