Nab-paclitaxel plus S-1 followed by gemcitabine-oxaliplatin as first-line alternating sequential treatment of pancreatic ductal adenocarcinoma.

Publisher: Oxford University Press Country of Publication: England NLM ID: 9607837 Publication Model: Print Cited Medium: Internet ISSN: 1549-490X (Electronic) Linking ISSN: 10837159 NLM ISO Abbreviation: Oncologist Subsets: MEDLINE

Publication: 2022- : Oxford : Oxford University Press
Original Publication: Dayton, Ohio : AlphaMed Press, c1996-

Albumins*/administration & dosage ; Albumins*/therapeutic use ; Albumins*/pharmacology ; Albumins*/adverse effects ; Antineoplastic Combined Chemotherapy Protocols*/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols*/pharmacology ; Carcinoma, Pancreatic Ductal*/drug therapy ; Carcinoma, Pancreatic Ductal*/mortality ; Carcinoma, Pancreatic Ductal*/pathology ; Deoxycytidine*/analogs & derivatives ; Deoxycytidine*/therapeutic use ; Deoxycytidine*/administration & dosage ; Deoxycytidine*/pharmacology ; Drug Combinations* ; Gemcitabine* ; Oxaliplatin*/therapeutic use ; Oxaliplatin*/pharmacology ; Oxaliplatin*/administration & dosage ; Oxonic Acid*/administration & dosage ; Oxonic Acid*/therapeutic use ; Paclitaxel*/administration & dosage ; Paclitaxel*/therapeutic use ; Paclitaxel*/pharmacology ; Paclitaxel*/adverse effects ; Pancreatic Neoplasms*/drug therapy ; Pancreatic Neoplasms*/mortality ; Pancreatic Neoplasms*/pathology ; Tegafur*/administration & dosage ; Tegafur*/therapeutic use ; Tegafur*/adverse effects; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies

Background: Alternating sequential administration of drugs may be a promising approach to overcome chemotherapy resistance in advanced pancreatic ductal adenocarcinoma (PDAC).
Methods: This study was an open-label, single-arm, and prospective trial included patients with untreated advanced PDAC. They received 2 cycles of NS regimen (nab-paclitaxel:125 mg/m2, intravenously injected on days 1 and 8, plus S-1:40-60 mg, orally twice per day for 1-14 days) followed by 2 cycles of GemOx regimen (gemcitabine, intravenously injected on days 1 and 8, and oxaliplatin: 130 mg/m2, intravenously injected on day 1). The primary efficacy endpoint was a progression-free survival rate at 6 months (PFSR-6m). The secondary efficacy endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Specific mRNA transcripts were used to explore survival associated genes.
Results: Forty-two patients received a minimum of one treatment cycle, and of these, 30 patients completed one alternating treatment consisting of 4 cycles. The PFSR-6m was 71% (95% CI = 58%-87%). The median PFS and OS were 6.53 months (95% CI = 6.03-8.43) and 11.4 months (95% CI = 9.8-14.4), respectively. Common grades 3-4 hematological AEs included neutropenia 30.9%, leukopenia 26.2%, anemia 2.4%, and thrombocytopenia in 11.9%. Patients with OS > 10 months showed high expression of HLA-DQA2 while melanoma-associated antigen genes (MAGE) were notably upregulated in patients with OS < 10 months.
Conclusion: The alternating sequential administration of the NS and GemOx regimens may be a novel approach for first-line chemotherapy in patients with advanced PDAC requiring further study (ClinicalTrials.gov Identifier: ChiCTR1900024867).
(© The Author(s) 2024. Published by Oxford University Press.)

Ann Oncol. 2004 Mar;15(3):433-9. (PMID: 14998845)
Cancer Chemother Pharmacol. 2016 Mar;77(3):595-603. (PMID: 26842789)
ESMO Open. 2018 Feb 23;3(2):e000313. (PMID: 29531840)
Oncotarget. 2017 Sep 28;8(54):92401-92410. (PMID: 29190925)
Ann Oncol. 2016 Apr;27(4):654-60. (PMID: 26802160)
Lancet. 2020 Jun 27;395(10242):2008-2020. (PMID: 32593337)
Cancer Res. 2014 Jun 1;74(11):2913-21. (PMID: 24840647)
Nat Rev Clin Oncol. 2018 Feb;15(2):81-94. (PMID: 29115304)
Oncologist. 2015 Feb;20(2):143-50. (PMID: 25582141)
Eur J Cancer. 2019 Jan;106:99-105. (PMID: 30476732)
Anticancer Res. 2010 Jul;30(7):3031-8. (PMID: 20683051)
Cell. 2018 Feb 8;172(4):841-856.e16. (PMID: 29395328)
Oncogene. 2014 Sep 11;33(37):4579-88. (PMID: 24662835)
N Engl J Med. 2011 May 12;364(19):1817-25. (PMID: 21561347)
Anticancer Res. 2011 Jun;31(6):2271-81. (PMID: 21737652)
Medicine (Baltimore). 2021 May 21;100(20):e26052. (PMID: 34011119)
Eur J Cancer. 2020 Nov;139:51-58. (PMID: 32977220)
Clin Epigenetics. 2018 Sep 5;10(1):115. (PMID: 30185218)
J Cancer Res Clin Oncol. 2021 May;147(5):1529-1536. (PMID: 33191450)
Rev Panam Salud Publica. 2015 Dec;38(6):506-14. (PMID: 27440100)
JAMA. 2020 Dec 8;324(22):2242-2244. (PMID: 33206137)
Ann Oncol. 2015 May;26(5):888-894. (PMID: 25669832)
Lancet Oncol. 2016 Jun;17(6):801-810. (PMID: 27160474)
Eur J Cancer. 2014 Dec;50(18):3116-24. (PMID: 25454414)
Br J Cancer. 2016 Mar 29;114(7):737-43. (PMID: 27022826)
J Clin Oncol. 2005 May 20;23(15):3509-16. (PMID: 15908661)
CA Cancer J Clin. 2023 Jan;73(1):17-48. (PMID: 36633525)
Cancer Chemother Pharmacol. 2018 Oct;82(4):655-660. (PMID: 30054709)
Cell. 2016 May 19;165(5):1092-1105. (PMID: 27133165)
Blood. 2016 Jan 28;127(4):420-5. (PMID: 26500339)
N Engl J Med. 2013 Oct 31;369(18):1691-703. (PMID: 24131140)

81773210 National Natural Science Foundation of China; JJZD2022-06 Harbin Medical University Cancer Hospital; 2022ZX06C10 Major Research and Development Program of Heilongjiang Province

Keywords: GemOX; Nab-paclitaxel plus S-1; pancreatic ductal adenocarcinoma; phase II; sequential treatment

0 (130-nm albumin-bound paclitaxel)
0 (Albumins)
0W860991D6 (Deoxycytidine)
0 (Drug Combinations)
0 (Gemcitabine)
04ZR38536J (Oxaliplatin)
5VT6420TIG (Oxonic Acid)
P88XT4IS4D (Paclitaxel)
150863-82-4 (S 1 (combination))
1548R74NSZ (Tegafur)

gemcitabine-oxaliplatin regimen

Date Created: 20240903 Date Completed: 20241108 Latest Revision: 20241119

20241120

PMC11546623

10.1093/oncolo/oyae207

39226089