Gemcitabine plus nab-paclitaxel for locally advanced or borderline resectable pancreatic cancer

Tsujimoto, Akiko; Sudo, Kentaro; Nakamura, Kazuyoshi; Kita, Emiri; Hara, Ryusuke; Takayama, Wataru; Ishii, Hiroshi; Yamaguchi, Taketo

doi:10.1038/s41598-019-52486-x

Cited by 19 publications

(8 citation statements)

References 21 publications

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“…Similarly, FOLFIRINOX with gemcitabine transitions 52% patients with borderline resectable disease to R0 outcomes (25). Retrospective data analysis of 30 patients with locally advanced or borderline resectable PDAC, who received neoadjuvant gemcitabine plus nab-paclitaxel, with and without subsequent S-1 therapy reveals that eight were amenable for surgery, and six achieved R0 resection (26). Collectively, this work demonstrates the potential to improve survival outcomes in traditionally non-operable patients and to expand current curative intent therapy.…”

Section: Diagnosis Of Pancreatic Adenocarcinomamentioning

confidence: 80%

Pancreatic Adenocarcinoma: Unconventional Approaches for an Unconventional Disease

et al. 2020

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This review highlights current treatments, limitations, and pitfalls in the management of pancreatic cancer and discusses current research in novel targets and drug development to overcome these clinical challenges. We begin with a review of the clinical landscape of pancreatic cancer, including genetic and environmental risk factors, as well as limitations in disease diagnosis and prevention. We next discuss current treatment paradigms for pancreatic cancer and the shortcomings of targeted therapy in this disease. Targeting major driver mutations in pancreatic cancer, such as dysregulation in the KRAS and TGF-β signaling pathways, have failed to improve survival outcomes compared to non-targeted chemotherapy; thus, we describe new advances in therapy such as Ras binding pocket inhibitors. We then review next-generation approaches in nanomedicine and drug delivery, focusing on preclinical advancements in novel optical probes, antibodies, small molecule agents, and nucleic acids to improve surgical outcomes in resectable disease, augment current therapies, expand druggable targets, and minimize morbidity. We conclude by summarizing progress in current research, identifying areas for future exploration in drug development and nanotechnology, and discussing future prospects for management of this disease. Clinical Snapshot of Pancreatic AdenocarcinomaPancreatic cancer is the most lethal common tumor in America. The five-year survival is estimated to be 9.3% among all cases and 2.9% among patients with metastatic disease, both lowest amongst all common tumors (1). With its rising incidence and unabated mortality, pancreatic cancer is the third leading cause of cancer related death, with a projection that it will the second by 2030 (Figure 1) (2,3). In 2019, pancreatic ductal adenocarcinoma (PDAC; 95% of patients) represented 3.2% of all new cancer cases, with an estimated 56,770 new cases and 45,750 deaths (7.5% of all cancer deaths) (1).

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Section: Diagnosis Of Pancreatic Adenocarcinomamentioning

confidence: 80%

Pancreatic Adenocarcinoma: Unconventional Approaches for an Unconventional Disease

et al. 2020

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“…Pooled proportions of prospective studies (n = 396) showed an overall resection rate of 42% (95% CI 24-61%) and an R0 resection rate of 22% (95% CI 10-36%) (Figure S1). [26,28,29,31,33,35,[37][38][39][40][44][45][46]) only. Due to heterogeneity among studies, a random effects model was used.…”

Section: Resection Ratesmentioning

confidence: 99%

“…Figure 2. Forest plots showing the pooled proportions of resections and R0 resections (defined as absence of tumor at the margin or a minimum distance between tumor and margin of >1 mm) of all patients (n = 739, refs [26,[28][29][30][31][33][34][35][36][37][38][39][40][41][42][43][44][45][46]…”

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confidence: 99%

Efficacy and Safety of Neoadjuvant Gemcitabine Plus Nab-Paclitaxel in Borderline Resectable and Locally Advanced Pancreatic Cancer—A Systematic Review and Meta-Analysis

Damm

Efremov

Birnbach

et al. 2021

Cancers

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Therapy with gemcitabine and nab-paclitaxel (GNP) is the most commonly used palliative chemotherapy, but its advantage in the neoadjuvant setting remains unclear. Accordingly, our aim is to evaluate the impact of first-line neoadjuvant therapy with GNP in patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC). A systematic search for published studies until August 2020 was performed. The primary endpoint included resection and R0 resection rates in the intention-to-treat population. Secondary endpoints were response rate, survival and toxicity. Among 21 studies, 950 patients who received neoadjuvant GNP were evaluated. Treatment with GNP resulted in surgical resection and R0 resection rates as follows: 49% (95% CI 30–68%) and 36% (95% CI 17–58%) for BRPC and 16% (95% CI 7–26%) and 11% (95% CI 5–19%) for LAPC, respectively. The objective response rates and the median overall survival (mOS) ranged from 0 to 67% and 12 to 30 months, respectively. Neutropenia (range 5–77%) and neuropathy (range 0–22%) were the most commonly reported grade 3 to 4 adverse events. Neoadjuvant chemotherapy with GNP can be performed safely and with valuable effects in patients with BRPC and LAPC. The utility of GNP in comparison to FOLFIRINOX in the neoadjuvant setting requires further investigation in prospective randomized trials.

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“…Preoperative chemotherapy (CTx) or chemoradiotherapy (CRTx) prolongs survival in pancreatic cancer patients [6,7]. However, 20-70% of patients are surgical candidates after CTx or CRTx, and indications for surgery vary between institutions [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Duration of Reduced CA19-9 Levels Is a Better Prognostic Factor Than Its Rate of Reduction for Unresectable Locally Advanced Pancreatic Cancer

Isayama

Ishii

Fujisawa

et al. 2021

Cancers

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A decrease in carbohydrate antigen (CA) 19-9 levels has been proposed as a prognostic marker for survival and recurrence in patients with pancreatic cancer. We evaluated the association between duration of reduced CA 19-9 levels during 6 months after treatment and long-term survival for 79 patients with unresectable locally advanced pancreatic cancer (LAPC). We calculated the differences between pretreatment and monthly CA19-9 levels. We categorized 71 patients with decreases in CA19-9 levels into three groups based on the duration of these reduced levels (>2, >3, and >4 months). The cut-off level for long-term (more than 2 years) survival was identified as a 44% reduction from the baseline, using a ROC curve. A reduction duration >2 months was not associated with overall survival (p = 0.1), while >3 months was significantly associated with survival (p =.04). In multivariate analysis, a reduction duration >3 months predicted a good long-term prognosis (odds ratio = 5.75; 95% confidence interval = 1.47–22.36; p < 0.01). In patients with unresectable LAPC, the duration of reduced CA19-9 levels for more than 3 months, rather than the rate of reduction in CA19-9 levels, during 6 months after treatment was significantly associated with good prognosis.

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Gemcitabine plus nab-paclitaxel for locally advanced or borderline resectable pancreatic cancer

Cited by 19 publications

References 21 publications

Pancreatic Adenocarcinoma: Unconventional Approaches for an Unconventional Disease

Pancreatic Adenocarcinoma: Unconventional Approaches for an Unconventional Disease

Efficacy and Safety of Neoadjuvant Gemcitabine Plus Nab-Paclitaxel in Borderline Resectable and Locally Advanced Pancreatic Cancer—A Systematic Review and Meta-Analysis

Duration of Reduced CA19-9 Levels Is a Better Prognostic Factor Than Its Rate of Reduction for Unresectable Locally Advanced Pancreatic Cancer

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