scholarly journals Capecitabine and oxaliplatin as first and second line treatment for locally advanced and metastatic pancreatic ductal adenocarcinoma

2017 ◽  
Vol 8 (6) ◽  
pp. 945-952 ◽  
Author(s):  
Andrea Bullock ◽  
Keith Stuart ◽  
Susanna Jacobus ◽  
Thomas Abrams ◽  
Raymond Wadlow ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Locally Advanced ◽  
Ductal Adenocarcinoma ◽  
Line Treatment ◽  
Second Line

scholarly journals Second-line treatment in patients with pancreatic ductal adenocarcinoma: A meta-analysis

Cancer ◽  
2017 ◽  
Vol 123 (23) ◽  
pp. 4680-4686 ◽  
Author(s):  
Mohamad Bassam Sonbol ◽  
Belal Firwana ◽  
Zhen Wang ◽  
Diana Almader-Douglas ◽  
Mitesh J. Borad ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Meta Analysis ◽  
Ductal Adenocarcinoma ◽  
Line Treatment ◽  
Second Line

Second-line treatment in patients with pancreatic ductal adenocarcinoma: A meta-analysis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15779-e15779
Author(s):  
Mohamad Bassam Sonbol ◽  
Belal Firwana ◽  
Zhen Wang ◽  
Daniel H. Ahn ◽  
Mitesh J. Borad ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Meta Analysis ◽  
Single Agent ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Ductal Adenocarcinoma ◽  
Line Treatment ◽  
Second Line ◽  
Modest Improvement ◽  
Random Effects Models

e15779 Background: There is paucity of data regarding the best available second-line treatment following progression on gemcitabine-based regimens in metastatic pancreatic ductal adenocarcinoma (PDAC). While a Nanoliposomal formulation of irinotecan (MM398) is considered a standard of care, there is conflicting data relating to the use of oxaliplatin in this setting. We performed a meta-analysis to determine the effectiveness of adding oxaliplatin (OX) or various irinotecan (IRI) formulations to a fluoropyrimidine (FP) as a second-line in PDAC patients. Methods: We searched different databases, including PubMed, Embase and Cochrane, to identify randomized controlled trials comparing FP monotherapy to FP combination therapy that includes either oxaliplatin (FPOX) or various irinotecan formulations (FPIRI) in PDAC patients who progressed after first-line treatment. Secondary analyses were planned to assess the effectiveness of FPOX and FPIRI compared to FP. Outcomes of interest included overall survival (OS) and progression-free survival (PFS). The overall effect was pooled using the DerSimonian and Laird random effects models. Results: Five studies (2 with FPIRI and 3 with FPOX) with 895 patients were identified. Patients randomized to FPIRI/FPOX had a significantly improved PFS (HR = 0.74, CI 0.62 to 0.89) and a trend towards an improved OS compared to FP monotherapy (HR = 0.88, CI 0.65 to 1.19). When comparing FPIRI to FP, there was an improvement in both PFS (HR = 0.64, CI 0.47 to 0.87) and OS (HR = 0.70, CI 0.55 to 0.89) in patients treated with the combination. Conversely, FPOX showed only a modest improvement in PFS (HR = 0.81, CI 0.67, 0.97) with no improvement in OS (HR = 1.03, CI 0.64 to 1.67). Conclusions: Combination chemotherapy with oxaliplatin or various irinotecan formulations seem to improve PFS vs. single agent FP. FPIRI, but not FPOX seem to confer an OS advantage. Oxaliplatin with FP following gemcitabine failure may need further confirmatory studies to establish its role in refractory pancreas cancer.

scholarly journals Efficacy and safety of second-line nab-paclitaxel plus gemcitabine after progression on FOLFIRINOX for unresectable or metastatic pancreatic ductal adenocarcinoma: multicenter retrospective analysis

2020 ◽  
Vol 12 ◽  
pp. 175883592092342 ◽  
Author(s):  
Heejung Chae ◽  
Hyehyun Jeong ◽  
Jaekyung Cheon ◽  
Hong Jae Chon ◽  
Hyewon Ryu ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Retrospective Analysis ◽  
Treatment Option ◽  
Progression Free Survival ◽  
Ductal Adenocarcinoma ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Free Survival ◽  
Grade 3

Background: FOLFIRINOX (fluorouracil, folinic acid, irinotecan plus oxaliplatin) is an effective standard first-line treatment option for advanced pancreatic ductal adenocarcinoma (PDAC). There is no clear consensus on the second-line treatment following progression on FOLFIRINOX. In this multicenter retrospective analysis, we evaluated the efficacy and tolerability of second-line nab-P/Gem (nab-paclitaxel and gemcitabine) after progression on FOLFIRNOX in PDAC. Methods: Patients with unresectable or metastatic PDAC who received nab-P/Gem after progression on FOLFIRINOX between February 2016 and February 2019 were identified from five referral cancer centers in South Korea. Baseline characteristics, treatment history, survival outcomes, and toxicity profile were obtained retrospectively from medical records. Results: A total of 102 patients treated with second-line nab-P/Gem for advanced PDAC after progression on FOLFIRINOX were included. At the time of nab-P/Gem, the median age was 60 years, with males comprising 49.0%, and most (75.5%) had metastatic disease. Patients received a median of three cycles (range 1–12) of nab-P/Gem. The median overall survival (OS) and progression-free survival (PFS) from the start of second-line nab-P/Gem therapy were 9.8 (95% CI, 8.9–10.6) and 4.6 months (3.7–5.5), respectively. A partial response was achieved in 8.5%, and the disease control rate was 73.6%. From the start of first-line FOLFIRIOX, the OS1+2 and PFS1+2 were 20.9 (15.7–26.1) and 13.9 (10.8–17.0) months, respectively, with a 2-year survival rate of 45.1%. There was no treatment-related mortality and grade ⩾3 toxicity was observed in 60.2%. Conclusion: Our results showed that nab-P/Gem was an effective and tolerable second-line treatment option in medically fit patients with advanced PDAC who progressed on first-line FOLFIRNOX. ClinicalTrials.gov identifier: NCT04133155

Impact of nab-paclitaxel-based second-line chemotherapy on the outcomes of pancreatic cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 483-483
Author(s):  
Neelakanta Dadi ◽  
Safi Shahda ◽  
Bert H. O'Neil ◽  
Amikar Sehdev
Keyword(s):  
Retrospective Study ◽  
Performance Status ◽  
Locally Advanced ◽  
Group Versus ◽  
Ductal Adenocarcinoma ◽  
Cancer Center ◽  
Line Treatment ◽  
Second Line ◽  
Second Line Chemotherapy ◽  
Line Chemotherapy

483 Background: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with no standard second line chemotherapies. We conducted a retrospective study with the primary aim to examine the effect of second line chemotherapy with nab-paclitaxel-based regimen on the overall survival (OS) and progression-free survival (PFS) of locally advanced and metastatic PDAC patients. Methods: Indiana University Simon Cancer Center (IUSCC) Cancer Registry was used to identify patients with locally advanced or metastatic PDAC between 2009 and 2015. Only patients who received second line chemotherapies were included in the study. These patients were divided in to two groups: a) nab-paclitaxel-based treatment and, b) non-nab-paclitaxel-based treatment. Demographic (age, race, gender, year of diagnosis, family history, comorbidity), clinical (histology, CA 19-9, bilirubin, tumor location, performance status, metastatic sites, chemotherapy, surgery or radiation) and outcome (OS, PFS) characteristics were obtained. OS and PFS were estimate by using Kaplan-Meier method and 95% CI. Cox proportional-hazard model was used for multivariate analysis. Results: Forty-seven (39%) and seventy-three (61%) patients received nab-paclitaxel-based and non-nab-paclitaxel-based second line chemotherapy, respectively. In the univariate analyses, nab-paclitaxel-based treatment was only associated with younger age (60.4 vs. 64 years; P = 0.02). The median PFS was 2.8 and 2.1 months (HR 0.62; 95% CI 0.38-1.02; P = 0.06), and the median OS was 7.5 and 4.7 months (HR 0.67; 95% CI 0.45-1.00; P = 0.05) in patients who received nab-paclitaxel based second line treatment versus not, respectively. Multivariate analyses adjusted for age showed a significantly improved PFS (adjusted HR 0.60, 95% CI 0.36-0.98; P = 0.04) and a suggestion of improved OS (adjusted HR 0.67; 95% CI 0.44-1.01, P = 0.05) in the nab-paclitaxel based second line treatment group versus not, respectively. Conclusions: In a single institution retrospective study, we report significant improvement in the PFS and a suggestion of improvement in the OS with nab-paclitaxel based treatment as compared with non-nab-paclitaxel based treatment in the second line setting.

scholarly journals Towards an optimal treatment algorithm for metastatic pancreatic ductal adenocarcinoma (PDA)

2018 ◽  
Vol 25 (1) ◽  
pp. 90 ◽  
Author(s):  
M. Uccello ◽  
M. Moschetta ◽  
G. Mak ◽  
T. Alam ◽  
C. Murias Henriquez ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Optimal Algorithm ◽  
Treatment Algorithm ◽  
Ductal Adenocarcinoma ◽  
Line Treatment ◽  
Second Line ◽  
New Paradigm ◽  
First Line ◽  
First Line Treatment

Chemotherapy remains the mainstay of treatment for advanced pancreatic ductal adenocarcinoma (pda). Two randomized trials have demonstrated superiority of the combination regimens folfirinox (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan) and gemcitabine plus nab-paclitaxel over gemcitabine monotherapy as a first-line treatment in adequately fit subjects. Selected pda patients progressing to first-line therapy can receive secondline treatment with moderate clinical benefit. Nevertheless, the optimal algorithm and the role of combination therapy in second-line are still unclear. Published second-line pda clinical trials enrolled patients progressing to gemcitabine-based therapies in use before the approval of nab-paclitaxel and folfirinox. The evolving scenario in second-line may affect the choice of the first-line treatment. For example, nanoliposomal irinotecan plus 5-fluouracil and leucovorin is a novel second-line option which will be suitable only for patients progressing to gemcitabinebased therapy. Therefore, clinical judgement and appropriate patient selection remain key elements in treatment decision. In this review, we aim to illustrate currently available options and define a possible algorithm to guide treatment choice. Future clinical trials taking into account sequential treatment as a new paradigm in pda will help define a standard algorithm.

Efficacy and safety of KN046 plus nab-paclitaxel/gemcitabine as first-line treatment for unresectable locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4138-4138
Author(s):  
Gang Jin ◽  
Shiwei Guo ◽  
Yanqiao Zhang ◽  
Yue Ma ◽  
Xiaodong Guo ◽  
...  
Keyword(s):  
Adverse Events ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Tumor Therapy ◽  
Locally Advanced ◽  
Tumour Response ◽  
Ductal Adenocarcinoma ◽  
Line Treatment ◽  
Efficacy And Safety ◽  
First Line ◽  
First Line Treatment

4138 Background: Pancreatic ductal adenocarcinoma（PDAC）is one of the most lethal malignancies worldwide and is characterized by extremely poor prognosis. Nab-paclitaxel plus gemcitabine has been recommended by international guidelines for first-line treatment of advanced PDAC but chemoresistance is difficult to avoid. Combination of immune checkpoint inhibitors (ICIs) and chemotherapy has demonstrated substantial promise for the treatment of several advanced malignancies. A few recent studies have begun to explore the effect of ICIs monotherapy or co in advanced PDAC with few meaningful results. KN046, a novel recombinant humanized bispecific antibody, can simultaneously block PD-1/PD-L1 and CTLA-4 pathways and restore T-cell immune response to tumor. The purpose of this study is to evaluate the efficacy and safety of KN046 plus nab-paclitaxel/gemcitabine as first-line treatment for unresectable locally advanced or metastatic PDAC. Methods: This ongoing phase II trial in China enrolled pts with histologically or cytologically confirmed unresectable locally advanced or metastatic PDAC who have ECOG PS of 0-1 and never received systemic anti-tumor therapy for advanced or metastatic diseases. KN046 (5mpk, Q2W) plus nab-paclitaxel (125mg/m2, D1, 8, 15, Q4W) and gemcitabine (1000mg/m2, D1, 8, 15, Q4W) were administered 4-6 cycles followed by KN046 (5mpk) maintenance therapy every 2 weeks. Tumour response was assessed according to RECIST 1.1 every 8 weeks. The primary endpoint is investigator-assessed ORR. Secondary endpoints are DCR, DOR, TTP, PFS, OS and safety. Results: As of December 15, 2020, 17 pts were enrolled, median (range) age was 56 (36-75) years, 9 pts ECOG 1, and 7 pts had liver metastases. Median KN046 exposure time was 9.5 wks. 9 pts were included in the efficacy analysis and 17 pts in the safety analysis. In best overall response assessment, there were 55.6% PR (5/9) and 33.3% SD (3/9). ORR was 55.6% (95% CI: 21.2̃86.3), and DCR was 88.9% (95% CI: 51.8̃99.7). The overall incidence of KN046 related treatment-emergent adverse events was 64.7%, with 29.4% were grade 3 TRAE. The most common KN046 related treatment-emergent adverse events (≥10%) were alanine aminotransferase increased (n = 5, 29.4%), nausea (n = 3, 17.6%), rash (n = 3, 17.6%), aspartate aminotransferase increased (n = 2, 11.8%), diarrhoea (n = 2, 11.8%), hyperphosphataemia (n = 2, 11.8%), pyrexia (n = 2, 11.8%), vomiting (n = 2, 11.8%). Conclusions: Combining KN046 with nab-paclitaxel and gemcitabine as first-line treatment for unresectable locally advanced or metastatic PDAC patients is safe and feasible, and lays the foundation for subsequent clinical trials. Clinical trial information: NCT04324307.

Predicting Surgical Margins in Patients With Borderline Resectable and Locally Advanced Pancreatic Cancer Undergoing Resection

2021 ◽  
pp. 000313482110111
Author(s):  
Weizheng Ren ◽  
Dimitrios Xourafas ◽  
Stanley W. Ashley ◽  
Thomas E. Clancy
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Ductal Adenocarcinoma ◽  
Resection Margins ◽  
Borderline Resectable ◽  
Stepwise Selection ◽  
R1 Resection ◽  
Positive Resection Margins

Background Many patients with borderline resectable/locally advanced pancreatic ductal adenocarcinoma (borderline resectable [BR]/locally advanced [LA] pancreatic ductal adenocarcinoma [PDAC]) undergoing resection will have positive resection margins (R1), which is associated with poor prognosis. It might be useful to preoperatively predict the margin (R) status. Methods Data from patients with BR/LA PDAC who underwent a pancreatectomy between 2008 and 2018 at Brigham and Women’s Hospital were retrospectively reviewed. Logistic regression analysis was used to evaluate the association between R status and relevant preoperative factors. Significant predictors of R1 resection on univariate analysis ( P < .1) were entered into a stepwise selection using the Akaike information criterion to define the final model. Results A total of 142 patients with BR/LA PDAC were included in the analysis, 60(42.3%) had R1 resections. In stepwise selection, the following factors were identified as positive predictors of an R1 resection: evidence of lymphadenopathy at diagnosis (OR = 2.06, 95% CI: 0.99-4.36, P = .056), the need for pancreaticoduodenectomy (OR = 3.81, 96% CI: 1.15-15.70, P = .040), extent of portal vein/superior mesenteric vein involvement at restaging (<180°, OR = 3.57, 95% CI: 1.00-17.00, P = .069, ≥180°, OR = 7,32, 95% CI: 1.75-39.87, P = .010), stable CA 19-9 serum levels (less than 50% decrease from diagnosis to restaging, OR = 2.27, 95% CI: 0.84-6.36 P = .107), and no preoperative FOLFIRINOX (OR = 2.17, 95% CI: 0.86-5.64, P = .103). The prognostic nomogram based on this model yielded a probability of achieving an R1 resection ranging from <5% (0 factors) to >70% (all 5 factors). Conclusions Relevant preoperative clinicopathological characteristics accurately predict positive resection margins in patients with BR/LA PDAC before resection. With further development, this model might be used to preoperatively guide surgical decision-making in patients with BR/LA PDAC.

scholarly journals The efficacy of radiofrequency ablation (RFA) in locally advanced pancreatic ductal adenocarcinoma

HPB ◽  
2021 ◽  
Vol 23 ◽  
pp. S316-S317
Author(s):  
O. Hadjicosta ◽  
D. Christou ◽  
A. Christodoulou ◽  
P. Hadjicostas
Keyword(s):  
Radiofrequency Ablation ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Locally Advanced ◽  
Ductal Adenocarcinoma
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