PMID- 35930304 OWN - NLM STAT- MEDLINE DCOM- 20230707 LR - 20231213 IS - 1549-490X (Electronic) IS - 1083-7159 (Print) IS - 1083-7159 (Linking) VI - 28 IP - 7 DP - 2023 Jul 5 TI - A Phase I Study of Gemcitabine/Nab-Paclitaxel/S-1 Chemotherapy in Patients With Locally Advanced or Metastatic Pancreatic Ductal Adenocarcinoma. PG - e575-e584 LID - 10.1093/oncolo/oyac146 [doi] AB - BACKGROUND: Systemic chemotherapy is the primary treatment in patients with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC). More effective treatment options are highly awaited. The aim of this study was to evaluate the toxicity and feasibility of gemcitabine/nab-paclitaxel/S-1 (GAS) chemotherapy on a 21-day cycle in patients with locally advanced or metastatic PDAC, determine the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of S-1 in this regimen, and explore preliminary efficacy. METHODS: Eligible patients with locally advanced or metastatic PDAC received GAS chemotherapy on a 21-day cycle. Fixed-dose nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2) were given intravenously on days 1 and 8. Different doses of S-1 were given orally twice daily from day 1 to day 14 in a 3+3 dose escalation design. According to patients; body surface area, the dose-escalation design was as follows: patients with a body surface area of 1.25-1.5 m2 received S-1 40 mg/day initially and the dose was increased to 60 mg or 80 mg. Patients with a body surface area of more than 1.5 m2 received S-1 60 mg/day initially and the dose was increased to 80 mg or 100 mg. The primary endpoints were to evaluate the toxicity and determine the DLT and MTD of S-1. The secondary endpoint was to evaluate efficacy, including best objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). adverse events (AEs) were evaluated according to the NCI-CTCAE 5.0. Tumor response was assessed using the RECIST 1.1. RESULTS: A total of 21 eligible patients were included. Due to the infrequence of patients with a body surface area of 1.25-1.5 m2, only 2 patients were included in cohort of S-1 40 mg. The dose-escalation for patients in this group failed to be enrolled completely. For patients with a body surface area of more than 1.5 m2, 3 DLTs in 7 patients were detected at cohort of S-1 100 mg (grade 3 thrombocytopenia with hemorrhage, grade 3 rash, and grade 3 mucositis/stomatitis). S-1 80 mg/day (body surface area: >1.5 m2) was considered to be the MTD in GAS chemotherapy on a 21-day cycle. No grade 4 AEs or treatment-related deaths were observed. The most commonly occurring hematologic AE of any grade was anemia (38.1%). The most frequent nonhematologic AEs of any grade were peripheral neuropathy (38.1%), dyspepsia (23.8%), constipation (23.8%), and alopecia (23.8%). Response assessment showed that the best ORR was 36.8% (7 of 19 patients) and the DCR was 94.7% (18 of 19 patients). The median PFS was 5.3 (95% CI, 4.6 to 6.0) months and the median OS was 10.3 (95% CI, 8.1 to 12.5) months. CONCLUSION: GAS chemotherapy (21-day cycle) with nab-paclitaxel 125 mg/m2, gemcitabine 1000 mg/m2, and S-1 80 mg/day (body surface area: >1.5 m2) was found to have acceptable toxicity and significant clinical control in patients with locally advanced or metastatic PDAC. We conclude that further trials with this combination are warranted. (Trial Identifier: ChiCTR1900027833 [chictr.org]). CI - (c) The Author(s) 2022. Published by Oxford University Press. FAU - Chang, Chen AU - Chang C AD - Department of Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, People's Republic of China. FAU - Li, Xiaofen AU - Li X AD - Department of Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, People's Republic of China. FAU - Cheng, Ke AU - Cheng K AD - Department of Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, People's Republic of China. FAU - Cai, Zhaolun AU - Cai Z AD - Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, People's Republic of China. FAU - Xiong, Junjie AU - Xiong J AD - Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, People's Republic of China. FAU - Lv, Wanrui AU - Lv W AD - Department of Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, People's Republic of China. FAU - Li, Ruizhen AU - Li R AD - Department of Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, People's Republic of China. FAU - Zhang, Pei AU - Zhang P AD - Department of Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, People's Republic of China. FAU - Cao, Dan AU - Cao D AUID- ORCID: 0000-0003-4486-2641 AD - Department of Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, People's Republic of China. LA - eng PT - Clinical Trial, Phase I PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Oncologist JT - The oncologist JID - 9607837 RN - 0 (Gemcitabine) RN - 0 (130-nm albumin-bound paclitaxel) RN - P88XT4IS4D (Paclitaxel) SB - IM MH - Humans MH - *Gemcitabine MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects MH - Paclitaxel MH - *Adenocarcinoma/pathology MH - Pancreatic Neoplasms PMC - PMC10322137 OTO - NOTNLM OT - S-1 OT - gemcitabine OT - nab-paclitaxel OT - pancreatic ductal adenocarcinoma OT - phase I COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/08/06 06:00 MHDA- 2023/07/07 06:43 PMCR- 2022/08/05 CRDT- 2022/08/05 11:43 PHST- 2022/03/13 00:00 [received] PHST- 2022/06/21 00:00 [accepted] PHST- 2023/07/07 06:43 [medline] PHST- 2022/08/06 06:00 [pubmed] PHST- 2022/08/05 11:43 [entrez] PHST- 2022/08/05 00:00 [pmc-release] AID - 6656410 [pii] AID - oyac146 [pii] AID - 10.1093/oncolo/oyac146 [doi] PST - ppublish SO - Oncologist. 2023 Jul 5;28(7):e575-e584. doi: 10.1093/oncolo/oyac146.