| 1. |
- Javed, Muhammad Ahsan, et al.
(författare)
-
Impact of intensified chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC) in clinical routine in Europe
- 2019
-
Ingår i: Pancreatology (Print). - : Elsevier. - 1424-3903 .- 1424-3911. ; 19:1, s. 97-104
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis. Gemcitabine is the standard chemotherapy for patients with metastatic pancreatic adenocarcinoma (MPA). Randomized clinical trials evaluating intensified chemotherapies including FOLFIRINOX and nab-paclitaxel plus gemcitabine (NAB+GEM) have shown improvement in survival. Here, we have evaluated the efficacy of intensified chemotherapy versus gemcitabine monotherapy in real-life settings across Europe.METHODS: A retrospective multi-center study including 1056 MPA patients, between 2012 and 2015, from nine centers in UK, Germany, Italy, Hungary and the Swedish registry was performed. Follow-up was at least 12 months. Cox proportional Harzards regression was used for uni- and multivariable evaluation of prognostic factors.RESULTS: Of 1056 MPA patients, 1030 (98.7%) were assessable for survival analysis. Gemcitabine monotherapy was the most commonly used regimen (41.3%), compared to FOLFIRINOX (n = 204, 19.3%), NAB+GEM (n = 81, 7.7%) and other gemcitabine- or 5-FU-based regimens (n = 335, 31.7%). The median overall survival (OS) was: FOLFIRINOX 9.9 months (95%CI 8.4-12.6), NAB+GEM 7.9 months (95%CI 6.2-10.0), other combinations 8.5 months (95%CI 7.7-9.3) and gemcitabine monotherapy 4.9 months (95%CI 4.4-5.6). Compared to gemcitabine monotherapy, any combination of chemotherapeutics improved the survival with no significant difference between the intensified regimens. Multivariable analysis showed an association between treatment center, male gender, inoperability at diagnosis and performance status (ECOG 1-3) with poor prognosis.CONCLUSION: Gemcitabine monotherapy was predominantly used in 2012-2015. Intensified chemotherapy improved OS in comparison to gemcitabine monotherapy. In real-life settings, the OS rates of different treatment approaches are lower than shown in randomized phase III trials.
|
|
| 2. |
- Le, Nha, et al.
(författare)
-
Prognostic and predictive markers in pancreatic adenocarcinoma
- 2016
-
Ingår i: Digestive and Liver Disease. - : Elsevier BV. - 1590-8658 .- 1878-3562. ; 48:3, s. 223-230
-
Forskningsöversikt (refereegranskat)abstract
- Pancreatic ductal adenocarcinoma is characterized by a poor prognosis and a low median survival, despite improvements observed for many other solid tumours. Intensive research efforts have been undertaken during the last decades to discover new prognostic and treatment predictive biomarkers for pancreatic ductal adenocarcinoma. The mainstay of medical treatment for the disease has been the well-tolerated nucleoside analogue, gemcitabine. The only targeted agent currently used in pancreatic ductal adenocarcinoma patients is the epithelial growth factor receptor inhibitor erlotinib in combination with gemcitabine. Recently, treatment regimens such as a combination of fluorouracilleucovorin-irinotecan-oxaliplatin (FOLFIRINOX) and the combination of nab-paclitaxel with gemcitabine have been introduced for metastatic pancreatic ductal adenocarcinoma. Although these treatment regimens significantly improve survival of patients, there are no good predictive biomarkers available that can be used to identify who would benefit most from them. Therefore, the search for predictive biomarkers that would facilitate personalization of chemotherapy is highly relevant.
|
|
| 3. |
- Le, Nha, et al.
(författare)
-
Real-world clinical practice of intensified chemotherapies for metastatic pancreatic cancer : results from a Pan-European questionnaire study
- 2016
-
Ingår i: Digestion. - : S. Karger AG. - 0012-2823 .- 1421-9867. ; 94:4, s. 222-229
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Recently, FOLFIRINOX and gemcitabine + nab-paclitaxel have been introduced as a novel intensified chemotherapy regimen for patients with metastasized pancreatic cancer. This study aims to analyze the real-world clinical practice with FOLFIRINOX and gemcitabine + nab-paclitaxel across Europe.Methods: Invitations to participate in an anonymous web-based questionnaire were sent via e-mail to 5,420 doctors in 19 European countries through the network of national gastroenterological, oncological, surgical and pancreatic societies as well as the European Pancreatic Club. The questionnaire consisted of 20 questions, 14 regarding the use of intensified chemotherapy, 4 regarding demographics of the participants, and 1 to verify the active involvement in the management of metastatic pancreatic cancer.Results: Two hundred and thirteen responses were received and 153 entries were valid for analysis. Of those, 63.4% came from an academic institution, 51% were oncologists, and 52% treated more than 25 cases per year. A majority of responses (71%) were from Italy (40%), Germany (23%), and Spain (8%). As first-line therapy, 11% used gemcitabine +/- erlotinib, 42% used FOLFIRINOX, and 47% used gemcitabine + nab-paclitaxel. Of the intensified regimens, both were applied to equal parts, but the likelihood of protocol deviation was higher when using FOLFIRINOX (p < 0.01). FOLFIRINOX was considered more toxic than gemcitabine + nab-paclitaxel (neutropenia 88 vs. 68%; polyneuropathy 42 vs. 41%; rapid deterioration 42 vs. 31%). FOLFIRINOX was rated to achieve longer survival with an acceptable quality of life (52 vs. 44%). Moreover, 57% of participants thought that gemcitabine + nab-paclitaxel should be the backbone for further clinical trials in pancreatic cancer.Conclusion: Intensified chemotherapy is widely used in pancreatic cancer patients in Europe following its recent clinical approval. Interestingly, nab-paclitaxel and FOLFIRINOX were used at comparable frequency although the latter had to be de-escalated more often.
|
|
| 4. |
- Schober, Marvin, et al.
(författare)
-
New Advances in the Treatment of Metastatic Pancreatic Cancer
- 2015
-
Ingår i: Digestion. - : S. Karger. - 0012-2823 .- 1421-9867. ; 92:3, s. 175-184
-
Forskningsöversikt (refereegranskat)abstract
- Background: Pancreatic ductal adenocarcinoma (PDAC) is characterised by an extremely poor overall survival (OS) compared to other solid tumours. As the incidence of the disease is rising and the treatment options are limited, PDAC is projected to be the 2nd leading cause of cancer-related deaths in the United States by 2030. A majority of patients are not eligible for curative resection at the time of diagnosis, and those that are resected will often relapse within the first few years after surgery. Summary: Until recently, the nucleoside analogue gemcitabine has been the standard of care for patients with non-resectable PDAC with only marginal effects on OS. In 2011, the gemcitabine-free FOLFIRINOX regimen (folinic acid, fluorouracil, irinotecan and oxaliplatin) showed a significant survival advantage for patients with metastatic PDAC in a phase III trial. In 2013, the Metastatic Pancreatic Adenocarcinoma Trial phase III trial with nano-formulated albumin-bound paclitaxel (nab-paclitaxel) in combination with gemcitabine also resulted in a significant survival extension compared to gemcitabine monotherapy. However, both intensified therapy regimens show a broad spectrum of side effects and patients need to be carefully selected for the most appropriate protocol. Key Message: In this study, recent advances in the chemotherapeutic options available to treat metastatic PDAC and their implications for today's treatment choices are reviewed.
|
|
