Efficacy and Safety of the Combination of Nano-Liposomal Irinotecan and 5-Fluorouracil/L-Leucovorin in Unresectable Advanced Pancreatic Cancer: A Real-World Study

Abstract Aim: This retrospective study investigated the efficacy and safety of nano-liposomal irinotecan (nal-IRI) plus 5-fluorouracil/l-leucovorin (5-FU/l-LV) treatment in the second-line or later setting for advanced pancreatic cancer under real-world conditions.Methods: Between June 2020 and September 2021, a total of 44 patients with unresectable advanced pancreatic cancer treated with nal-IRI + 5-FU/l-LV in our affiliated hospitals were included. The prognosis, predictive factors (including systemic inflammation-based prognostic indicators), and adverse events were investigated.Results: The median age was 68 (interquartile range [IQR] 62-73) years old, and 22 patients (50.0%) were male. Concerning tumor factors, 9 patients (20.5%) had local advanced disease, and 35 patients (79.5%) had metastases. Twenty-five of the 44 patients were receiving second-line treatment, and 19 were receiving third-line or later treatment. The median overall survival (OS) and progression free survival (PFS) were 9.0 (range, 0.7-15.4) months and 4.4 (range, 0.6-15.4) months, respectively. The overall response rate (ORR) was 5.3%. The disease control rate (DCR) was 44.7%. Patients with a neutrophil-to-lymphocyte ratio (NLR) of >2.7 had a significant risk of a poor OS (HR=0.275, P=0.017). Adverse events were manageable, although gastrointestinal symptoms and neutropenia were observed. The most common grade ≥3 adverse event was neutropenia, which was reported in 20% of patients.Conclusions: Nal-IRI + 5-FU/l-LV therapy was considered to be a useful regimen as second-line or later treatment for unresectable advanced pancreatic cancer, even in clinical practice.

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Gemcitabine Plus Nab-Paclitaxel as Second-Line Chemotherapy following FOLFIRINOX in Patients with Unresectable Pancreatic Cancer: A Single-Institution, Retrospective Analysis

Chemotherapy ◽

10.1159/000517244 ◽

2021 ◽

pp. 1-7

Author(s):

Kotone Hayuka ◽

Hiroyuki Okuyama ◽

Akitsu Murakami ◽

Yoshihiro Okita ◽

Takamasa Nishiuchi ◽

...

Keyword(s):

Pancreatic Cancer ◽

Adverse Events ◽

Advanced Pancreatic Cancer ◽

Progression Free Survival ◽

Unresectable Pancreatic Cancer ◽

Line Treatment ◽

Second Line ◽

Free Survival ◽

Common Grade ◽

Grade 3

Introduction: Patients with advanced pancreatic cancer have a poor prognosis. FOLFIRINOX (FFX) and gemcitabine plus nab-paclitaxel (GnP) have been established as first-line treatment, but they have not been confirmed as second-line treatment after FFX. The aim of this study was to evaluate the safety and efficacy of GnP as second-line therapy after FFX in patients with unresectable pancreatic cancer. Methods: Twenty-five patients with unresectable pancreatic cancer were enrolled. The patients were treated with GnP after FFX between September 2015 and September 2019. Tumor response, progression-free survival (PFS), overall survival (OS), and incidence of adverse events were evaluated. Results: The response rate, disease control rate, median PFS, and median OS were 12%, 96%, 5.3 months, and 15.6 months, respectively. The common grade 3 or 4 adverse events were neutropenia (76%) and anemia (16%). Conclusions: GnP after FOLFIRINOX is expected to be one of the second-line recommendations for patients with unresectable pancreatic cancer.

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Efficacy and Safety of Bevacizumab in Combination with Chemotherapy for Colorectal Cancer – A Real World Study in China

10.21203/rs.3.rs-29014/v1 ◽

2020 ◽

Author(s):

Tao Shen ◽

Xian-Shuo Cheng ◽

Wei-Xun Chunyu ◽

Hong-Tao Zhang ◽

Cui-Feng Xia ◽

...

Keyword(s):

Colorectal Cancer ◽

Adverse Events ◽

Real World ◽

Large Scale ◽

Progression Free Survival ◽

Secondary Outcome ◽

Second Line ◽

Efficacy And Safety ◽

First Line ◽

Demographic Subgroups

Abstract Background Large scale randomized trials have demonstrated that bevacizumab in addition to chemotherapy as first-line or second-line treatment has significant survival benefits. We aim to explore the clinical impact of bevacizumab in combination with chemotherapy in first-line or second-line in patients with colorectal cancer (CRC). Methods The medical records of patients with CRC who received bevacizumab at first or second-line of treatment were collected retrospectively. The primary outcome of the study was to evaluate the efficacy of bevacizumab in combination with chemotherapy by survival endpoints i.e. overall survival (OS) and progression-free survival (PFS) and the secondary outcome was to evaluate its safety by incidence of adverse events (AE). Results Fifty-one patients with CRC had met the selection criteria for treatment with bevacizumab to either cetuximab or FOLFOX or both. The median age was 54 years. During follow-up, ten patients had exhibited progression after treatment while 5 patients died. The median OS and PFS of the overall population were not reached. The Cox proportional regression analysis revealed no significant prognostic factors of OS and PFS for treatment with bevacizumab in various demographic subgroups. The 1-year PFS rates of all 51 patients was 76%. The 1-year and 3-year OS rates for all 51 patients were 95% and 88%, respectively. Toxicities were usually mild in nature, with nausea, vomiting, hand and foot syndrome, neutropenia, asthenia and palpitation being the commonly reported adverse events. Conclusion In this real-world setting, the efficacy and safety of bevacizumab in combination with chemotherapy is limited and further research is warranted as to whether bevacizumab with chemotherapy is an optimal treatment as first-line or second-line therapy in Chinese CRC patients.

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Observational retrospective evaluation of treatment with liposomal irinotecan plus fluorouracil/leucovorin for metastatic pancreatic cancer patients: An Italian large real-world analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.660 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 660-660 ◽

Cited By ~ 1

Author(s):

Antonio Pellino ◽

Chiara Manai ◽

Valeria Merz ◽

Mario Scartozzi ◽

Michele Milella ◽

...

Keyword(s):

Pancreatic Cancer ◽

Real World ◽

Cox Regression ◽

Phase Iii ◽

Metastatic Pancreatic Cancer ◽

Rank Test ◽

Efficacy And Safety ◽

Real World Data ◽

Liposomal Irinotecan ◽

Ecog Ps

660 Background: In the NAPOLI I phase III trial, Nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) showed better outcome compared to 5FU/LV in patients with metastatic Pancreatic Cancer (MPC) progressed to 1st- line gemcitabine-based therapy. Aim of this study is to explore the real-world efficacy and safety of 5FU/LV-nal-IRI by a compassionate use programme and to identify potential prognostic factors that could affect survival in this setting. Methods: This is a retrospective multi-center analysis including patients with MPC who received 5FU/LV-nal-IRI after failure of a gemcitabine-based therapy. Survival analyses were carried out by the Kaplan-Meier method. Univariate and multivariate analyses were performed by using the log-rank test and the Cox regression. Results: A total of 296 pts (median age, 69 years, range 30-82; 50% male; ECOG PS 0, 44%) were treated at 11 Italian institutions from June 2016 and November 2018. 34% of the pts have been previously resected on their primary tumor, and 76% received gemcitabine-nabpaclitaxel as 1st - line treatment. 5FU/LV-nal-IRI has been administered as 2nd - line in 72% of the pts, while in 23% of the cases as 3rd - line or more. The median OS was 7.1 months [95% confidence interval (CI) 6.1 - 8.1] and the median PFS was 3.3 months (95% CI 2.9 - 3.6). At six months, OS and PFS rate were 53.4% and 31.4% respectively. ORR was 12% and DCR was 40%. 52% of pts received more than 4 cycle with dose reduction in 148 pts (50%). Most common grade 3 toxicities were neutropenia (14%), diarrhea (11%), anemia (3%), nausea (3%), fatigue (3%), mucositis (2%) and vomiting (1%). Baseline characteristics associated with better OS were ECOG PS 0, normal CEA, neutrophil-to-lymphocyte ratio ≤5 and haemoglobin ≥11 g/dL. Conclusions: These real-world data confirm the efficacy and safety of 5FU/LV-nal-IRI in patients with MPC progressed to a gemcitabine-based therapy, with outcome comparable to NAPOLI-1 even in a less selected population and with more active 1st - line combination therapy. In this cohort, well known prognostic markers has been confirmed, as expected.

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PANCREOX: A Randomized Phase III Study of Fluorouracil/Leucovorin With or Without Oxaliplatin for Second-Line Advanced Pancreatic Cancer in Patients Who Have Received Gemcitabine-Based Chemotherapy

Journal of Clinical Oncology ◽

10.1200/jco.2016.68.5776 ◽

2016 ◽

Vol 34 (32) ◽

pp. 3914-3920 ◽

Cited By ~ 92

Author(s):

Sharlene Gill ◽

Yoo-Joung Ko ◽

Christine Cripps ◽

Annie Beaudoin ◽

Sukhbinder Dhesy-Thind ◽

...

Keyword(s):

Pancreatic Cancer ◽

Adverse Events ◽

Group Performance ◽

Advanced Pancreatic Cancer ◽

Phase Iii ◽

Life Questionnaire ◽

Second Line ◽

European Organization ◽

Phase Iii Study ◽

Previously Treated

Purpose The standard of care for second-line therapy in patients with advanced pancreatic cancer after gemcitabine-based therapy is not clearly defined. The CONKO-003 phase III study reported a survival benefit with second-line fluorouracil (FU) and oxaliplatin using the oxaliplatin, folinic acid, and FU (OFF) regimen. 1 PANCREOX was a phase III multicenter trial to evaluate the benefit of FU and oxaliplatin administered as modified FOLFOX6 (mFOLFOX6; infusional fluorouracil, leucovorin, and oxaliplatin) versus infusional FU/leucovorin (LV) in this setting. Patients and Methods Patients with confirmed advanced pancreatic cancer who were previously treated with gemcitabine therapy and with an Eastern Cooperative Oncology Group performance status of 0-2 were eligible. A total of 108 patients were randomly assigned to receive biweekly mFOLFOX6 or infusional FU/LV until progression. Progression-free survival (PFS) was the primary end point. Results Baseline patient characteristics were similar in both arms. No difference was observed in PFS (median, 3.1 months v 2.9 months; P = .99). Overall survival (OS) was inferior in patients assigned to mFOLFOX6 (median, 6.1 months v 9.9 months; P = .02). Increased toxicity was observed with the addition of oxaliplatin, with grade 3/4 adverse events occurring in 63% of patients who received mFOLFOX6 and 11% of those who received FU/LV. More patients in the mFOLFOX6 arm withdrew from study due to adverse events than in the FU/LV arm (20% v 2%), whereas the use of postprogression therapy was significantly higher in the FU/LV arm (25% v 7%; P = .015). No significant differences were observed in time to deterioration on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 global health scale. Conclusion No benefit was observed with the addition of oxaliplatin, administered as mFOLFOX6, versus infusional FU/LV in patients with advanced pancreatic cancer previously treated with first-line gemcitabine.

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Severe neutropenia is associated with better clinical outcomes in patients with advanced pancreatic cancer who received modified FOLFIRINOX therapy

10.20944/preprints201809.0540.v1 ◽

2018 ◽

Cited By ~ 1

Author(s):

Yunami Yamada ◽

Hironori Fujii ◽

Daichi Watanabe ◽

Hiroko Kato-Hayashi ◽

Koichi Ohata ◽

...

Keyword(s):

Pancreatic Cancer ◽

Adverse Events ◽

Cancer Patients ◽

Clinical Outcomes ◽

Advanced Pancreatic Cancer ◽

Significant Risk ◽

Multivariate Logistic Regression Analysis ◽

Incidence Rates ◽

Severe Neutropenia ◽

High Level

Modified FOLFIRINOX is effective for advanced pancreatic cancer but frequently causes severe neutropenia. The present study was designed to investigate the influence of severe neutropenia on clinical outcomes in advanced pancreatic cancer patients receiving modified FOLFIRINOX. Fifty-one advanced pancreatic cancer patients who received modified FOLFIRINOX during January 2014 and May 2018 were subjects of the present study. Adverse events, including neutropenia, were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. Median overall survival (OS) was determined as the primary endpoint, while median time to treatment failure (TTF), overall response rate (ORR), and the incidence of other adverse events were measured as secondary endpoints. Severe neutropenia (grade≥3) occurred in 39 patients (76.4%), in which high level of total bilirubin (>0.6mg/dL) was a significant risk as assessed by a multivariate logistic regression analysis. Median duration of OS was significantly longer in patients with severe neutropenia than in those without it (15.2 months versus 7.2 months, P=0.032). Moreover, there was a significant correlation between OS and the grade of neutropenia (R=0.306, P=0.029). ORR tended to be higher, though not significantly, in patients with severe neutropenia. In contrast, the incidence rates of other adverse events were not different between the two groups. Severe neutropenia is an independent predictor of prognosis in advanced pancreatic cancer patients received modified FOLFIRNOX therapy.

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Is gemcitabine effective for pancreatic cancer after progression to FOLFIRINOX?

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.489 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 489-489

Author(s):

Bruno Melo Fernandes ◽

Rafael Caparica Bitton ◽

Jorge Sabbaga ◽

Paulo Marcelo Hoff

Keyword(s):

Pancreatic Cancer ◽

Disease Progression ◽

Advanced Pancreatic Cancer ◽

Significant Risk ◽

Progression Free Survival ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Line Chemotherapy ◽

First Line Treatment

489 Background: Cytotoxic chemotherapy with FOLFIRINOX (5-Fluoracil + Irinotecan + Oxaliplatin) is considered the standard treatment for fit patients (pts) with pancreatic adenocarcinoma. Disease progression after FOLFIRINOX invariably occurs, and there is no definition on the optimal strategy for the second-line treatment of these pts. Gemcitabine is effective for advanced pancreatic cancer as first-line treatment, but its role after FOLFIRINROX progression is unknown. The present study aims to assess the efficacy of gemcitabine for treatment of advanced pancreatic cancer after progression to FOLFIRINOX. Methods: Single-institution, retrospective analysis of all pts consecutively diagnosed with advanced pancreatic cancer between January/2010, and October/2015, who received Gemcitabine as second line chemotherapy after progression to first line chemotherapy with FOLFIRINOX. Tumor responses were assessed through RECIST 1.1. PFS and OS were calculated using Kaplan Meier method. Results: 28 pts were included in our analysis. Median age was 55 years (38-75), and 19 pts (67%) were male. The median ECOG was 1 (0-2). Pts received a median of 9 cycles of FOLFIRINOX as first line treatment (1-27), with an objective (ORR) response rate of 39%. The median number of second-line Gemcitabine cycles was 3 (1-8), with an ORR of 3%, and a 17% rate of disease control (stable disease + partial response). Five patients (18%) discontinued second line Gemcitabine due to toxicities and the remaining 23 (82%) due to disease progression. Median overall survival was 5.6 months (0,36-11,5) and median progression-free survival was 2 months (0.2-7.7). Grade ≥ 3 toxicities with Gemcitabine were experienced by 18% of the patients. No treatment-related deaths were reported. Conclusions: Gemcitabine after progression to FOLFIRINOX presented a modest activity on the present study, with prospective trials being necessary to further assess this issue. Due to the palliative goal of the treatment, with the objective of improving patient´s quality of life, the significant risk of treatment-related adverse events and the low efficacy of Gemcitabine should be considered before prescribing Gemcitabine routinely as a second-line treatment for pancreatic cancer.

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Second-Line Gemcitabine Plus Nab-Paclitaxel for Patients with Unresectable Advanced Pancreatic Cancer after First-Line FOLFIRINOX Failure

Journal of Clinical Medicine ◽

10.3390/jcm8060761 ◽

2019 ◽

Vol 8 (6) ◽

pp. 761 ◽

Cited By ~ 3

Author(s):

Naoki Mita ◽

Takuji Iwashita ◽

Shinya Uemura ◽

Kensaku Yoshida ◽

Yuhei Iwasa ◽

...

Keyword(s):

Pancreatic Cancer ◽

Adverse Events ◽

Advanced Pancreatic Cancer ◽

Progression Free Survival ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Secondary Endpoints ◽

Grade 3 ◽

First Line Treatment

FOLFIRINOX (FX) and gemcitabine (GEM) plus nab-paclitaxel (GnP) have been reported as effective regimens for unresectable advanced pancreatic cancer (APC). FX may be more effective but is also associated with more adverse events (AEs). Therefore, first-line treatment with FX followed by second-line GnP may be appropriate. Aims: To assess the safety and efficacy of second-line GnP for patients with APC after first-line FX failure. Methods: This study was a multicenter prospective phase II study evaluating second-line GnP in patients with APC after failed first-line FX. The primary endpoint was response rate (RR), and the secondary endpoints were overall survival (OS), progression free survival (PFS), and the frequency and degree of adverse events (AEs). Results: Thirty patients (14 male; median age, 64 years) were enrolled. The RR was 13.3%, with a median follow-up time of 9.3 months. The median OS and PFS were 7.6 and 3.8 months, respectively. From the beginning of first-line treatment, the median OS and PFS were 14.2 and 9.3 months, respectively. Grade 3 or 4 AEs were seen in 70% of patients. Conclusion: Second-line GnP after FX failure for patients with APC could be more effective than GEM alone. Further comparison studies are warranted.

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Real World Evidence on Second-Line Palliative Chemotherapy in Advanced Pancreatic Cancer

Frontiers in Oncology ◽

10.3389/fonc.2020.01176 ◽

2020 ◽

Vol 10 ◽

Author(s):

Emma Gränsmark ◽

Nellie Bågenholm Bylin ◽

Hakon Blomstrand ◽

Mats Fredrikson ◽

Elisabeth Åvall-Lundqvist ◽

...

Keyword(s):

Pancreatic Cancer ◽

Real World ◽

Palliative Chemotherapy ◽

Advanced Pancreatic Cancer ◽

Second Line ◽

Real World Evidence

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Raising the Bar in Advanced Pancreatic Cancer

Oncology & Hematology Review (US) ◽

10.17925/ohr.2017.13.01.19 ◽

2017 ◽

Vol 13 (01) ◽

pp. 19

Author(s):

Sharlene Gill ◽

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Advanced Pancreatic Cancer ◽

Second Line ◽

First Line ◽

New Agents ◽

Level 1 ◽

Liposomal Irinotecan ◽

Line Setting ◽

Do So

Pancreatic cancer remains one of our greatest clinical challenges. In the last 5 years we have witnessed the introduction of new agents into our armamentarium, which has fortunately translated into incremental improvements in overall survival. We have level 1 evidence for the use of FOLFIRINOX and nab-paclitaxel in the first-line setting; however, the generalizability of randomized studies in the second-line setting has been less compelling. The use of oxaliplatin and 5-fluorouracil (5FU) post-gemcitabine progression was shown to improve survival in the CONKO-003 trial but failed to do so in the PANCREOX trial. Nano-liposomal irinotecan in combination with 5FU in pre-treated patients yielded an improved survival in the NAPOLI-1 trial, presenting an option in this setting. However, these trials were largely conducted in an era of first-line gemcitabine monotherapy, which is no longer a standard practice. Better evidence with contemporary first-line regimens is needed in order to define the optimal post-progression strategy in advanced pancreatic cancer.

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Severe Neutropenia is Associated with Better Clinical Outcomes in Patients with Advanced Pancreatic Cancer Who Receive Modified FOLFIRINOX Therapy

Cancers ◽

10.3390/cancers10110454 ◽

2018 ◽

Vol 10 (11) ◽

pp. 454 ◽

Cited By ~ 4

Author(s):

Yunami Yamada ◽

Hironori Fujii ◽

Daichi Watanabe ◽

Hiroko Kato-Hayashi ◽

Koichi Ohata ◽

...

Keyword(s):

Pancreatic Cancer ◽

Adverse Events ◽

Cancer Patients ◽

Clinical Outcomes ◽

Bolus Injection ◽

Advanced Pancreatic Cancer ◽

Significant Risk ◽

Total Bilirubin Level ◽

Severe Neutropenia ◽

Prior History

While modified FOLFIRINOX therapy is effective for treating advanced pancreatic cancer, it frequently causes severe neutropenia. The present study investigated the effect of severe neutropenia on clinical outcomes in advanced pancreatic cancer patients who received modified FOLFIRINOX. The study subjects were 51 patients (30 males and 21 females) with advanced pancreatic cancer who received modified FOLFIRINOX (2h bolus injection of oxaliplatin at 85 mg/m2, 2 h bolus injection of L-leucovorin at 200 mg/m2, 90min bolus injection of irinotecan at 150 mg/m2, followed by continuous infusion of 5-fluorouracil for 46 h at 2400 mg/m2 without bolus 5-fluorouracil) during the period from January 2014 to May 2018. No patients had prior history of chemotherapy. Adverse events, including neutropenia, were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. Median overall survival (OS) was the primary endpoint, while median time to treatment failure (TTF), overall response rate (ORR), and the incidence of other adverse events were secondary endpoints. Severe neutropenia (grade ≥3) occurred in 39 patients (76.4%), and Cox proportional hazard analysis identified high total bilirubin level as a significant risk factor. Median duration of OS was significantly longer in patients with severe neutropenia than in those without it (21.3 months versus 8.9 months, p = 0.020). Moreover, there was a significant correlation between OS and the grade of neutropenia (r = 0.306, p = 0.029). ORR tended to be higher, though not significantly, in patients with severe neutropenia. In contrast, the incidence rates of other adverse events were not different between the two groups. Severe neutropenia is an independent predictor of prognosis in advanced pancreatic cancer patients received modified FOLFIRINOX therapy.

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