1. Scheduling nab-paclitaxel combined with gemcitabine as first-line treatment for metastatic pancreatic adenocarcinoma
- Author
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Richard J. Ellis, Harpreet Wasan, Karen McAdam, S. Arif, Lisa Bax, Roopinder Gillmore, Jonathan Wadsley, Duncan I. Jodrell, Sebastian Cummins, Albrecht Neesse, Pippa Corrie, Yuk Ting Ma, Daniel H. Palmer, Rebecca Brais, J. Evans, David Propper, Aarthi Gopinathan, A. Chhabra, Martin Scott-Brown, R. Skells, Andrea Machin, K. Dalchau, A. Dayim, P. Bundi, Christopher Isherwood, Bristi Basu, C. Lwuji, John Bridgewater, David A. Tuveson, Alan Anthoney, Lucy Wall, S Falk, Juan W. Valle, Wendi Qian, Valle, J. W. [0000-0002-1999-0863], Bridgewater, J. [0000-0001-9186-1604], Apollo - University of Cambridge Repository, Valle, JW [0000-0002-1999-0863], and Bridgewater, J [0000-0001-9186-1604]
- Subjects
Oncology ,Male ,Cancer Research ,medicine.medical_specialty ,Paclitaxel ,Deoxycytidine ,Drug Administration Schedule ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Albumins ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Carcinoma ,Chemotherapy ,Humans ,Progression-free survival ,631/67/1504/1713 ,631/67/1059/99 ,030304 developmental biology ,Aged ,Aged, 80 and over ,0303 health sciences ,Manchester Cancer Research Centre ,business.industry ,ResearchInstitutes_Networks_Beacons/mcrc ,Hazard ratio ,article ,Pancreatic cancer ,Metastatic Pancreatic Adenocarcinoma ,Middle Aged ,medicine.disease ,Gemcitabine ,Confidence interval ,Progression-Free Survival ,Clinical trial ,Pancreatic Neoplasms ,030220 oncology & carcinogenesis ,Concomitant ,Female ,business ,medicine.drug ,Carcinoma, Pancreatic Ductal - Abstract
Background Nab-paclitaxel plus gemcitabine (nabP+gemcitabine) offers modest survival gains for patients with metastatic pancreatic ductal adenocarcinoma (PDAC). Sequential scheduling of nabP+gemcitabine in a PDAC mouse model improved efficacy; this hypothesis was tested in a clinical trial. Methods Patients with previously untreated metastatic PDAC were randomised to receive nabP+gemcitabine administered either concomitantly on the same day, or sequentially, with gemcitabine administered 24 h after nabP. The primary outcome measure was progression-free survival (PFS). Secondary outcome measures were objective response rate (ORR), overall survival (OS), safety, quality of life (QoL) and predictive biomarkers. Results In total, 71 patients received sequential (SEQ) and 75 concomitant (CON) treatment. Six-month PFS was 46% with SEQ and 32% with CON scheduling. Median PFS (5.6 versus 4.0 months, hazard ratio [HR] 0.67, 95% confidence interval [95% CI] 0.47–0.95, p = 0.022) and ORR (52% versus 31%, p = 0.023) favoured the SEQ arm; median OS was 10.2 versus 8.2 months (HR 0.93, 95% CI 0.65–1.33, p = 0.70). CTCAE Grade ≥3 neutropaenia incidence doubled with SEQ therapy but was not detrimental to QoL. Strongly positive tumour epithelial cytidine deaminase (CDA) expression favoured benefit from SEQ therapy (PFS HR 0.31, 95% CI 0.13–0.70). Conclusions SEQ delivery of nabP+gemcitabine improved PFS and ORR, with manageable toxicity, but did not significantly improve OS. Clinical trial registration ISRCTN71070888; ClinialTrials.gov (NCT03529175).
- Published
- 2021
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