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 ◽  
...  
2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15779-e15779
Author(s):  
Mohamad Bassam Sonbol ◽  
Belal Firwana ◽  
Zhen Wang ◽  
Daniel H. Ahn ◽  
Mitesh J. Borad ◽  
...  

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.


2020 ◽  
Vol 12 ◽  
pp. 175883592092342 ◽  
Author(s):  
Heejung Chae ◽  
Hyehyun Jeong ◽  
Jaekyung Cheon ◽  
Hong Jae Chon ◽  
Hyewon Ryu ◽  
...  

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


2018 ◽  
Vol 25 (1) ◽  
pp. 90 ◽  
Author(s):  
M. Uccello ◽  
M. Moschetta ◽  
G. Mak ◽  
T. Alam ◽  
C. Murias Henriquez ◽  
...  

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.


2017 ◽  
Vol 8 (6) ◽  
pp. 945-952 ◽  
Author(s):  
Andrea Bullock ◽  
Keith Stuart ◽  
Susanna Jacobus ◽  
Thomas Abrams ◽  
Raymond Wadlow ◽  
...  

2021 ◽  
Vol 139 ◽  
pp. 109672
Author(s):  
Jing Chen ◽  
Shuxue Liu ◽  
Yude Tang ◽  
Xiongbiao Zhang ◽  
Mingming Cao ◽  
...  

2020 ◽  
Vol 13 (1) ◽  
pp. 79-84
Author(s):  
Dilara Akhoundova Sanoyan ◽  
Cäcilia S. Reiner ◽  
Panagiota Papageorgiou ◽  
Alexander R. Siebenhüner

Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at an advanced or metastatic stage, when curative surgery is not recommended. Therefore, the prognosis is poor for this dismal disease, with only 1–2% of the patients reaching the 5-year survival follow-up. Current advances in systemic treatment with gemcitabine regimens, specifically polychemotherapy with gemcitabine plus nab-paclitaxel or other multidrug regimens such as FOLFIRINOX in the first line, have improved disease control over time. This higher efficacy of systemic treatment enables metastatic PDAC patients to receive second-line treatment more often nowadays. Currently, there is only one regimen for second-line treatment approved by the EMA, FDA, and Swissmedic, based on the phase III NAPOLI-1 study. In this case report, we present an outstanding response to sequential treatment with gemcitabine plus nab-paclitaxel followed by second-line treatment with nal-irinotecan plus 5-fluorouracil.


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