Nab-paclitaxel/gemcitabine combination is more effective than gemcitabine alone in locally advanced, unresectable pancreatic cancer – A GISCAD phase II randomized trial

Cascinu, Stefano; Berardi, Rossana; Bianco, Roberto; Bilancia, Domenico; Zaniboni, Alberto; Ferrari, Daris; Mosconi, S.; Spallanzani, Andrea; Cavanna, Luigi; Leo, Silvana; Negri, Francesca; Beretta, Giordano D.; Sobrero, Alberto; Banzi, M.; Morabito, Alberto; Bittoni, Alessandro; Marciano, Roberta; Ferrara, Domenica; Noventa, Silvia; Piccirillo, Maria Carmela; Labianca, Roberto; Mosconi, Cristina; Casadei-Gardini, Andrea; Gallo, Ciro; Perrone, Francesco

doi:10.1016/j.ejca.2021.02.023

Cited by 7 publications

(8 citation statements)

References 19 publications

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“…The trial showed the following outcomes: median time to treatment failure (primary endpoint) 9.0 months, median progression-free survival 10.9 months, median OS 18.8 months, disease control rate 77.6%, response rate 33.6%. The toxicities were in line with those reported in the GAP trial, and no adjuvant treatment after resection was planned [79].…”

Section: Neo-adjuvant and Perioperative Chemotherapysupporting

confidence: 69%

“…Key neo-adjuvant studies in locally advanced PDAC are summarized in Table 4. Nab-paclitaxel and gemcitabine combination chemotherapy was investigated in the phase II GAP trial [79]. The trial randomized 124 locally advanced PDAC patients to receive 3 cycles of gemcitabine with or without nab-paclitaxel as neo-adjuvant treatment.…”

Section: Neo-adjuvant and Perioperative Chemotherapymentioning

confidence: 99%

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Neoadjuvant Treatment for Pancreatic Adenocarcinoma: A False Promise or an Opportunity to Improve Outcome?

Khakoo

Petrillo

Salati

et al. 2021

Cancers

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Pancreatic ductal adenocarcinoma (PDAC) has an aggressive tumor biology and is associated with poor survival outcomes. Most patients present with metastatic or locally advanced disease. In the 10–20% of patients with upfront resectable disease, surgery offers the only chance of cure, with the addition of adjuvant chemotherapy representing an established standard of care for improving outcomes. Despite resection followed by adjuvant chemotherapy, at best, 3-year survival reaches 63.4%. Post-operative complications and poor performance mean that around 50% of the patients do not commence adjuvant chemotherapy, and a significant proportion do not complete the intended treatment course. These factors, along with the advantages of early treatment of micrometastatic disease, the ability to downstage tumors, and the increase in R0 resection rates, have increased interest in neo-adjuvant treatment strategies. Here we review biomarkers for early diagnosis of PDAC and patient selection for a neo-adjuvant approach. We also review the current evidence for different chemotherapy regimens in this setting, as well as the role of chemoradiotherapy and immunotherapy, and we discuss ongoing trials.

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Section: Neo-adjuvant and Perioperative Chemotherapysupporting

confidence: 69%

Section: Neo-adjuvant and Perioperative Chemotherapymentioning

confidence: 99%

Neoadjuvant Treatment for Pancreatic Adenocarcinoma: A False Promise or an Opportunity to Improve Outcome?

Khakoo

Petrillo

Salati

et al. 2021

Cancers

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“…Intensive chemotherapy regimens, such as gemcitabine + nab-paclitaxel, FOLFIRI-NOX, and PAXG, are currently available for LAPC [4][5][6]. Although the optimal therapy schedule has not been defined, the use of multi-agent chemotherapy before SBRT correlates with negative margins upon resection [26].…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, a systematic review and meta-analysis showed a median survival of 24.2 months in first-line treatment of LAPC with FOLFIRINOX, longer than that reported with gemcitabine [4]. As for gemcitabine + nab-paclitaxel, a randomized phase 2 trial in LAPC showed a reduction of disease progression rate after 3 months compared with gemcitabine alone (25.4% vs. 45.6%), along with a higher response rate (27% vs. 5.3%) and a positive effect on progression-free survival (PFS; 7 vs. 4 months) [5]. Promising results have also come from other combination regimens, such as PAXG; indeed, a randomized phase 2 trial that evaluated the addition of cisplatin and capecitabine to gemcitabine and nab-paclitaxel reported a 1-year PFS rate of 58% (vs. 39% in the control arm) and an OS rate at 18 months of 69% (vs. 54% in the control arm) [6].…”

Section: Introductionmentioning

confidence: 99%

Multimodal Treatment with GEMOX Plus Helical Tomotherapy in Unresectable Locally Advanced Pancreatic Cancer: A Pooled Analysis of Two Phase 2 Studies

et al. 2021

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In locally advanced pancreatic cancer (LAPC), the combination of chemotherapy and radiotherapy is a widely used treatment option. We performed a pooled analysis, including an exploratory analysis for prognostic and predictive factors, of two phase 2 trials including 73 patients with LAPC, treated with gemcitabine and oxaliplatin (GEMOX) and hypofractionated tomotherapy. With a median follow-up of 36 months (range 1–65), median progression-free (PFS) and overall survival (OS) were 10.2 (95% confidence interval [CI] 7.8–13.2) and 14.3 (95% CI 12.0–18.1) months, respectively. The overall resectability rate was 23.3% (95% CI 13.6–33.0), and the R0 resection rate was 13.7% (95% CI 5.8–21.6). In the multivariate analysis, ECOG performance status (PS) 0 and low levels of CA 19–9 were associated with improved OS and PFS. Concerning OS, log(CA19–9) resulted in a hazard ratio (HR) of 1.20 (95% CI 1.02–1.42), p = 0.027. For ECOG PS 0, HR was 1.00; for PS 1, HR was 2.69 (95% CI 1.46–4.96); for PS 2, HR was 4.18 (95% CI 0.90–19.46); p = 0.003. Low CA19–9 levels were also predictive for resection, with an odds ratio of 0.71 (95% CI 0.52–0.97), p = 0.034. In conclusion, GEMOX and hypofractionated radiotherapy is a treatment option in LAPC. Further studies are needed to identify differences in tumor biology, which may help to predict resectability and prognosis.

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“…Pancreatic cancerous organoids, generated for 24 h in liquid pearls, responded to #138-10D extract treatment, after 48 h incubation, in a manner equivalent to 80 µM Gemcitabine [10][11][12] used in therapy as a first-line treatment alone for pancreatic cancer (Figure 1). Thus, comparable results were observed with a concentration of 80 µg/mL of #138-10D extract, which represents an equivalent concentration of 40 µM CBD.…”

Section: Pancreatic Cancerous Organoids Generated In Liquid Pearlsmentioning

confidence: 99%

Cannabis sativa Extract Induces Apoptosis in Human Pancreatic 3D Cancer Models: Importance of Major Antioxidant Molecules Present Therein

et al. 2022

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In recent years, interest in Cannabis sativa L. has been rising, as legislation is moving in the right direction. This plant has been known and used for thousands of years for its many active ingredients that lead to various therapeutic effects (pain management, anti-inflammatory, antioxidant, etc.). In this report, our objective was to optimize a method for the extraction of cannabinoids from a clone of Cannabis sativa L. #138 resulting from an agronomic test (LaFleur, Angers, FR). Thus, we wished to identify compounds with anticancer activity on human pancreatic tumor cell lines. Three static maceration procedures, with different extraction parameters, were compared based on their median inhibitory concentration (IC50) values and cannabinoid extraction yield. As CBD emerged as the molecule responsible for inducing apoptosis in the human pancreatic cancer cell line, a CBD-rich cannabis strain remains attractive for therapeutic applications. Additionally, while gemcitabine, a gold standard drug in the treatment of pancreatic cancer, only triggers cell cycle arrest in G0/G1, CBD also activates the cell signaling cascade to lead to programmed cell death. Our results emphasize the potential of natural products issued from medicinal hemp for pancreatic cancer therapy, as they lead to an accumulation of intracellular superoxide ions, affect the mitochondrial membrane potential, induce G1 cell cycle arrest, and ultimately drive the pancreatic cancer cell to lethal apoptosis.

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Nab-paclitaxel/gemcitabine combination is more effective than gemcitabine alone in locally advanced, unresectable pancreatic cancer – A GISCAD phase II randomized trial

Cited by 7 publications

References 19 publications

Neoadjuvant Treatment for Pancreatic Adenocarcinoma: A False Promise or an Opportunity to Improve Outcome?

Neoadjuvant Treatment for Pancreatic Adenocarcinoma: A False Promise or an Opportunity to Improve Outcome?

Multimodal Treatment with GEMOX Plus Helical Tomotherapy in Unresectable Locally Advanced Pancreatic Cancer: A Pooled Analysis of Two Phase 2 Studies

Cannabis sativa Extract Induces Apoptosis in Human Pancreatic 3D Cancer Models: Importance of Major Antioxidant Molecules Present Therein

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