Gemcitabine/nab-Paclitaxel versus FOLFIRINOX for palliative first-line treatment of advanced pancreatic cancer: A propensity score analysis

Riedl, Jakob M.; Posch, Florian; Horvath, Lena; Gantschnigg, Antonia; Renneberg, Felix; Schwarzenbacher, E.; Moik, Florian; Barth, Dominik A.; Rossmann, Christopher; Stotz, Michael; Schaberl-Moser, Renate; Pichler, Martin; Stöger, Herbert; Greil, Richard; Djanani, Angela; Schlick, Konstantin; Gerger, Armin

doi:10.1016/j.ejca.2021.03.040

Cited by 36 publications

(50 citation statements)

References 31 publications

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“…Two distinct chemotherapeutic regimens currently recognize the first-line approach in progressive PDAC, namely, FOLFIRINOX (folinic acid, 5-fluorouracil, irinotecan, oxaliplatin) and gemcitabine (Gem) plus nab-paclitaxel ( Riedl et al, 2021 ). Although FOLFIRINOX provides significant results in improving both overall and median progression-free survival, its toxicity drastically restricts administration for patients with good performance status ( Damm et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Integrating Gemcitabine-Based Therapy With AdipoRon Enhances Growth Inhibition in Human PDAC Cell Lines

et al. 2022

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Pancreatic ductal adenocarcinoma (PDAC) accounts for 90% of all pancreatic cancers. Albeit its incidence does not score among the highest in cancer, PDAC prognosis is tremendously fatal. As a result of either aggressiveness or metastatic stage at diagnosis, chemotherapy constitutes the only marginally effective therapeutic approach. As gemcitabine (Gem) is still the cornerstone for PDAC management, the low response rate and the onset of resistant mechanisms claim for additional therapeutic strategies. The first synthetic orally active adiponectin receptor agonist AdipoRon (AdipoR) has recently been proposed as an anticancer agent in several tumors, including PDAC. To further address the AdipoR therapeutic potential, herein we investigated its pharmacodynamic interaction with Gem in human PDAC cell lines. Surprisingly, their simultaneous administration revealed a more effective action in contrasting PDAC cell growth and limiting clonogenic potential than single ones. Moreover, the combination AdipoR plus Gem persisted in being effective even in Gem-resistant MIA PaCa-2 cells. While a different ability in braking cell cycle progression between AdipoR and Gem supported their cooperating features in PDAC, mechanistically, PD98059-mediated p44/42 MAPK ablation hindered combination effectiveness. Taken together, our findings propose AdipoR as a suitable partner in Gem-based therapy and recognize the p44/42 MAPK pathway as potentially involved in combination outcomes.

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Section: Introductionmentioning

confidence: 99%

Integrating Gemcitabine-Based Therapy With AdipoRon Enhances Growth Inhibition in Human PDAC Cell Lines

et al. 2022

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Section: Resultsmentioning

confidence: 99%

“…Albeit not reaching statistical significance, patients who underwent fist-line treatment with Gemcitabine/nab-Paclitaxel had a markedly elevated risk of ATE compared with patients treated with FOLFIRINOX. This could potentially be explained by residual confounding due to the higher age and worse comorbidity profile in the Gemcitabine/nab-Paclitaxel group, 26 however, might also be related to the administered treatment itself, warranting further exploration. In contrast to previous studies, no significant association between onset of ATE and worse outcome was observed in our cohort.…”

Section: Discussionmentioning

confidence: 99%

“…In brief, patients treated with FOLFIRINOX were significantly younger, had a better ECOG performance status, and had fewer comorbidities compared with patients receiving Gemcitabine/nab-Paclitaxel. 26 Eighty-one patients (18%) of the overall cohort had a history of VTE prior to the initiation of palliative chemotherapy, including 57 patients (13%) with cancer-associated VTE and 24 patients (5%) with VTE in past medical history. The assignment of prior VTE events to the "cancer-associated" VTE group was made in case that the index diagnostic and therapeutic work-up for the VTE event led to the subsequent diagnosis of pancreatic cancer or in case the VTE occurred from time of diagnosis until treatment start of palliative firstline chemotherapy (i.e., study baseline).…”

Section: Study Cohortmentioning

confidence: 99%

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Patterns of Thromboembolism in Patients with Advanced Pancreatic Cancer Undergoing First-Line Chemotherapy with FOLFIRINOX or Gemcitabine/nab-Paclitaxel

et al. 2021

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Introduction: Recent advances in prophylactic anticoagulation and antineoplastic treatment for aPC warrant an updated reassessment of thromboembolic risk in this population. This multicenter retrospective cohort study aims to comprehensively characterize incidence, risk factors and outcomes of venous (VTE) and arterial thromboembolism (ATE) in homogenously treated patients with aPC. Methods: Four-hundred-fifty-five patients with aPC undergoing palliative 1st-line chemotherapy (Gemcitabine/nab-Paclitaxel (GN) or FOLIRINOX) were included. Primary outcomes were objectively confirmed VTE and/or ATE. Results: Over a median follow-up of 26 months, 86 VTE (cumulative incidence: 20.0% [95% confidence interval (CI): 16.3-24.0]) and 11 ATE events (cumulative incidence: 2.8% [95%CI: 1.5-4.9]) were observed. VTE diagnosis was associated with increased mortality (transition hazard ratio (THR): 1.59 [95%CI 1.21-2.09]) and increased risk of disease progression (THR: 1.47 [95%CI: 1.08-2.01]), while the impact of ATE on mortality was numerically but not statistically significant (THR: 1.85 [95%CI: 0.87-3.94]). The strongest predictor of increased VTE risk was history of cancer-associated VTE (subdistribution hazard ratio (SHR) 3.29 [95%CI: 2.09-5.18]), while the Khorana-score (SHR 0.78 [0.57-1.06]) failed to predict VTE risk. A history of cerebrovascular disease was associated with markedly increased ATE risk (SHR: 22.05 [95%CI: 6.83-71.22], p<0.001), especially ischemic stroke. Risk of VTE/ATE did not significantly differ according to type of 1st line chemotherapy. Conclusion: Patients with aPC undergoing palliative 1st-line chemotherapy with FOLFIRINOX or GN face a high risk for VTE/ATE and its diagnosis is linked to worse clinical outcomes. VTE-risk prediction models have limited ability to sub-stratify thrombotic events in this high-risk scenario.

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“…Continued testing of GnP in different groups of patients with advanced pancreatic cancer, such as elderly patients and patients with poor physical performance ( 87 – 89 ); 2. Comparing the efficacy and safety of GnP with FOLFIRINOX (a conventional chemotherapy regimen) for pancreatic cancer ( 90 – 93 ); 3. Testing new multidrug combination regimens based on nab-paclitaxel ( 94 – 97 ); and 4.…”

Section: Efficacy Of Nab-paclitaxel In Non-sarcoma Malignanciesmentioning

confidence: 99%

Albumin-Bound Paclitaxel: Worthy of Further Study in Sarcomas

Tian

Yao

2022

Front. Oncol.

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Taxanes (paclitaxel and docetaxel) play an important role in the treatment of advanced sarcomas. Albumin-bound paclitaxel (nab-paclitaxel) is a new kind of taxane and has many advantages compared with paclitaxel and docetaxel. Nab-paclitaxel is currently approved for the treatment of advanced breast, non-small cell lung, and pancreatic cancers. However, the efficacy of nab-paclitaxel in sarcomas has not been reviewed. In this review, we first compare the similarities and differences among nab-paclitaxel, paclitaxel, and docetaxel and then summarize the efficacy of nab-paclitaxel against various non-sarcoma malignancies based on clinical trials with reported results. The efficacy and clinical research progress on nab-paclitaxel in sarcomas are also summarized. This review will serve as a good reference for the application of nab-paclitaxel in clinical sarcoma treatment studies and the design of clinical trials.

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Gemcitabine/nab-Paclitaxel versus FOLFIRINOX for palliative first-line treatment of advanced pancreatic cancer: A propensity score analysis

Cited by 36 publications

References 31 publications

Integrating Gemcitabine-Based Therapy With AdipoRon Enhances Growth Inhibition in Human PDAC Cell Lines

Integrating Gemcitabine-Based Therapy With AdipoRon Enhances Growth Inhibition in Human PDAC Cell Lines

Patterns of Thromboembolism in Patients with Advanced Pancreatic Cancer Undergoing First-Line Chemotherapy with FOLFIRINOX or Gemcitabine/nab-Paclitaxel

Albumin-Bound Paclitaxel: Worthy of Further Study in Sarcomas

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