|Table of Contents|

Observation on the efficacy of nab-paclitaxel for tri-weekly and dose-dense chemotherapy in the treatment of advanced pancreatic cancer

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 20
Page:
3805-3811
Research Field:
Publishing date:

Info

Title:
Observation on the efficacy of nab-paclitaxel for tri-weekly and dose-dense chemotherapy in the treatment of advanced pancreatic cancer
Author(s):
SUN Ning; FAN Xiaona; LI Hengzhen; DAI Yisheng; JIANG Dan; CHEN Zhuo; LU Baiqi; LI Zhiwei
Department of Gastrointestinal Oncology,Harbin Medical University Cancer Hospital,Heilongjiang Harbin 150081,China.
Keywords:
pancreatic cancer; nab-paclitaxel; dose-dense; survival benefits; safety
PACS:
R735.9
DOI:
10.3969/j.issn.1672-4992.2023.20.016
Abstract:
Objective:To explore the clinical efficacy and safety of conventional,tri-weekly nab-paclitaxel chemotherapy and dose-dense nab-paclitaxel chemotherapy in the first-line treatment of unresectable pancreatic cancer.Methods：From January 2016 to December 2021,medical records of patients with unresectable pancreatic cancer who received combination chemotherapy with tri-weekly,conventional nab-paclitaxel (conventional group) or dose-dense nab-paclitaxel (dose-dense group) at our hospital were retrospectively collected to compare the survival benefit of patients.The primary endpoints were progression-free survival (PFS) and overall survival (OS).The objective response rate (ORR),disease control rate (DCR),and safety were secondary endpoints.Results:The study comprised 136 participants,of whom 40 participants got conventional nab-paclitaxel chemotherapy,and 96 participants had dose-dense nab-paclitaxel chemotherapy.The median PFS in the conventional group was 5.5 months ［95% confidence interval (CI):4.6~7.7］,while in the dose-dense group it was 5.9 months (95%CI:4.4~6.8) ［hazard ratio (HR)=0.95,95%CI:0.63~1.41,P=0.77］.The median OS in the conventional group was 8.6 months (95%CI:7.2~12.6),while in the dose-dense group it was 8.9 months (95%CI:7.3~10.8)(HR=0.99,95%CI:0.65~1.50,P=0.95).The PFS and OS between the two groups were not significantly different.The ORR were 32.5% and 27.1% in the conventional and dose-dense groups,respectively (P=0.52),and the DCR was 62.5% and 66.7% in the two groups,respectively (P=0.64),which did not reach statistical differences.Neutropenia(5.0% vs 27.1%),leukopenia (5.0% vs 18.8%),and anemia (10.0% vs 15.6%) were the most frequent grade 3/4 hematological adverse events in the conventional and dense-dose groups,respectively.Conclusion：We discovered that the survival benefits of conventional,tri-weekly nab-paclitaxel chemotherapy were comparable to those of dose-dense nab-paclitaxel chemotherapy.On the contrary,the conventional group had the advantage of better convenience,the risks of hematological toxicity were easier to control,more accessible to avoid,and safer.

References:

［1］SUNG H,FERLAY J,SIEGEL RL,et al.Global cancer statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries［J］.CA Cancer J Clin,2021,71(3):209-249.
［2］VON HOFF DD,ERVIN T,ARENA FP,et al.Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine［J］.N Engl J Med,2013,369(18):1691-1703.
［3］RIEDL JM,POSCH F,HORVATH L,et al.Gemcitabine/nab-Paclitaxel versus FOLFIRINOX for palliative first-line treatment of advanced pancreatic cancer:A propensity score analysis［J］.Eur J Cancer,2021,151,3-13.
［4］ZHANG W,DU C,SUN Y,et al.Nab-paclitaxel plus S-1 as first-line followed by S-1 maintenance for advanced pancreatic adenocarcinoma:a single-arm phase II trial［J］.Cancer Chemother Pharmacol,2018,82(4):655-660.
［5］ZONG Y,YUAN J,PENG Z,et al.Nab-paclitaxel plus S-1 versus nab-paclitaxel plus gemcitabine as first-line chemotherapy in patients with advanced pancreatic ductal adenocarcinoma:a randomized study［J］.J Cancer Res Clin Oncol,2021,147(5):1529-1536.
［6］KATSUMATA N.Dose-dense therapy is of benefit in primary treatment of ovarian cancer? In favor［J］.Ann Oncol,2011,22(Suppl 8):viii29-viii32.
［7］KATSUMATA N,YASUDA M,ISONISHI S,et al.Long-term results of dose-dense paclitaxel and carboplatin versus conventional paclitaxel and carboplatin for treatment of advanced epithelial ovarian,fallopian tube,or primary peritoneal cancer (JGOG 3016):a randomised,controlled,open-label trial［J］.Lancet Oncol,2013,14(10):1020-1026.
［8］CLAMP AR,JAMES EC,MCNEISH IA,et al.Weekly dose-dense chemotherapy in first-line epithelial ovarian,fallopian tube,or primary peritoneal cancer treatment (ICON8):overall survival results from an open-label,randomised,controlled,phase 3 trial［J］.Lancet Oncol,2022,23(7):919-930.
［9］ALVES RC,FERNANDES RP,ELOY JO,et al.Characteristics,properties and analytical methods of paclitaxel:a review［J］.Crit Rev Anal Chem,2018,48(2):110-118.
［10］IBRAHIM NK,DESAI N,LEGHA S,et al.Phase I and pharmacokinetic study of ABI-007,a Cremophor-free,protein-stabilized,nanoparticle formulation of paclitaxel［J］.Clin Cancer Res,2002,8(5):1038-1044.
［11］JOERGER M.Metabolism of the taxanes including nab-paclitaxel［J］.Expert Opin Drug Metab Toxicol,2015,11(5):691-702.
［12］SPARREBOOM A,SCRIPTURE CD,TRIEU V,et al.Comparative preclinical and clinical pharmacokinetics of a cremophor-free,nanoparticle albumin-bound paclitaxel (ABI-007) and paclitaxel formulated in Cremophor (Taxol)［J］.Clin Cancer Res,2005,11(11):4136-4143.
［13］KUNDRANDA MN,NIU J.Albumin-bound paclitaxel in solid tumors:clinical development and future directions［J］.Drug Des Devel Ther,2015,9,3767-3777.
［14］NYMAN DW,CAMPBELL KJ,HERSH E,et al.Phase I and pharmacokinetics trial of ABI-007,a novel nanoparticle formulation of paclitaxel in patients with advanced nonhematologic malignancies［J］.J Clin Oncol,2005,23(31):7785-7793.
［15］SCHILLER JH,STORER B,TUTSCH K,et al.Phase I trial of 3-hour infusion of paclitaxel with or without granulocyte colony-stimulating factor in patients with advanced cancer［J］.J Clin Oncol,1994,12(2):241-248.
［16］DESAI N,TRIEU V,YAO Z,et al.Increased antitumor activity,intratumor paclitaxel concentrations,and endothelial cell transport of cremophor-free,albumin-bound paclitaxel,ABI-007,compared with cremophor-based paclitaxel［J］.Clin Cancer Res,2006,12(4):1317-1324.
［17］LEGHA SS,TENNEY DM,KRAKOFF IR.Phase I study of taxol using a 5-day intermittent schedule［J］.J Clin Oncol,1986,4(5):762-766.
［18］NORTON L,SIMON R.The Norton-Simon hypothesis revisited［J］.Cancer Treat Rep,1986,70(1):163-169.
［19］VON HOFF DD,RAMANATHAN RK,BORAD MJ,et al.Gemcitabine plus nab-paclitaxel is an active regimen in patients with advanced pancreatic cancer:a phase I/II trial［J］.J Clin Oncol,2011,29(34):4548-4554.
［20］ZHANG DS,WANG DS,WANG ZQ,et al.Phase I/II study of albumin-bound nab-paclitaxel plus gemcitabine administered to Chinese patients with advanced pancreatic cancer［J］.Cancer Chemother Pharmacol,2013,71(4):1065-1072.
［21］QUAN Q,WANG Y,WANG F,et al.Real world first-line treatments and outcomes of Nab-Paclitaxel plus Gemcitabine,mFOLFIRINOX and GEMOX in unresectable pancreatic cancer from a Chinese single institution［J］.Curr Oncol,2020,28(1):209-219.
［22］CHANG C,LI X,CAO D.Combination of gemcitabine,nab-paclitaxel,and S-1(GAS) as the first-line treatment for patients with locally advanced or advanced pancreatic ductal adenocarcinoma:study protocol for an open-label,single-arm phase I study［J］.BMC Cancer,2021,21(1):545.
［23］LI JA,XU XF,HAN X,et al.Nab-Paclitaxel plus S-1 shows increased antitumor activity in patient-derived pancreatic cancer xenograft mouse models［J］.Pancreas,2016,45(3):425-433.
［24］QIN Y,HAN X,WANG L,et al.A phase I study of different doses and frequencies of pegylated recombinant human granulocyte-colony stimulating factor (PEG rhG-CSF) in patients with standard-dose chemotherapy-induced neutropenia［J］.Chin J Cancer Res,2017,29(5):402-410.
［25］CRAWFORD J,BECKER PS,ARMITAGE JO,et al.Myeloid growth factors,version 2.2017,NCCN clinical practice guidelines in oncology［J］.J Natl Compr Canc Netw,2017,15(12):1520-1541.
［26］WANG C,ZHU S,MIAO C,et al.Safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor during concurrent chemoradiotherapy for small-cell lung cancer:a retrospective,cohort-controlled trial［J］.BMC Cancer,2022,22(1):542.
［27］MOURI A,KAIRA K,SHIONO A,et al.Clinical significance of primary prophylactic pegylated-granulocyte-colony stimulating factor after the administration of ramucirumab plus docetaxel in patients with previously treated non-small cell lung cancer［J］.Thorac Cancer,2019,10(4):1005-1008.
［28］WU Q,LI Q,ZHANG J,et al.Comparison of primary and secondary prophylaxis using PEGylated recombinant human granulocyte-stimulating factor as a cost-effective measure in malignant neoplasms:a multicenter retrospective study［J］.Front Pharmacol,2021,12,690874.
［29］GOLDSTEIN D,VON HOFF DD,MOORE M,et al.Development of peripheral neuropathy and its association with survival during treatment with nab-paclitaxel plus gemcitabine for patients with metastatic adenocarcinoma of the pancreas:A subset analysis from a randomised phase III trial (MPACT)［J］.Eur J Cancer,2016,52：85-91.

Memo

Memo:
北京医学奖励基金会（编号:YXJL-2021-0678-0574）；北京希思科临床肿瘤学研究基金会（编号:Y-HS2017-033）;海燕科研基金重点项目（编号:JJZD2022-06）
Last Update: 1900-01-01