Is gemcitabine effective for pancreatic cancer after progression to FOLFIRINOX?

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.

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

2019 ◽  
Vol 8 (6) ◽  
pp. 761 ◽  
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.

scholarly journals FOLFIRINOX after first-line gemcitabine-based chemotherapy in advanced pancreatic cancer: a retrospective comparison with FOLFOX and FOLFIRI schedules

2020 ◽  
Vol 12 ◽  
pp. 175883592094797
Author(s):  
Francesca Foschini ◽  
Fabiana Napolitano ◽  
Alberto Servetto ◽  
Roberta Marciano ◽  
Eleonora Mozzillo ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Optimal Sequence ◽  
Line Chemotherapy

Background: Pancreatic adenocarcinoma is the fourth leading cause of cancer-related death. In cases with metastasis, the combination of 5-fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) or gemcitabine-based chemotherapy regimens are considered the standard of care. However, the optimal sequence of these regimens is unclear. Methods: This retrospective study initially evaluated 186 patients with locally advanced/metastatic pancreatic cancer at three Italian institutions between February 2013 and October 2019. All patients had progressed after receiving gemcitabine-based first-line chemotherapy and were subsequently offered second-line FOLFIRINOX, FOLFOX-6, or FOLFIRI treatment. This study evaluated progression-free survival (PFS), overall survival from the start of second-line treatment (OS2), overall survival from the start of first-line treatment (OS1), and safety outcomes. Results: A total of 77 patients received ⩾4 cycles of second-line chemotherapy and were considered eligible: 15 patients received FOLFIRINOX, 32 patients received FOLFOX-6, and 30 patients received FOLFIRI. The FOLFIRINOX group had median PFS of 26.29 weeks and median OS2 of 47.86 weeks, while the FOLFIRI group had median PFS of 10.57 weeks and median OS2 of 25.00 weeks ( p = 0.038). No significant differences were observed between the FOLFIRINOX and FOLFOX-6 groups in terms of PFS (26.29 weeks versus 23.07 weeks) or OS2 (47.86 weeks versus 42.00 weeks). The most common grade 3–4 toxicities were anemia, neutropenia, and thrombocytopenia, which occurred more frequently in the FOLFIRINOX and FOLFOX-6 groups. Conclusion: Relative to the FOLFIRI regimen, the FOLFIRINOX regimen had a favorable toxicity profile and better survival outcomes. No significant differences were observed relative to the FOLFOX-6 regimen.

Second-line chemotherapy in advanced pancreatic cancer: A retrospective, single-center analysis

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15187-15187 ◽  
Author(s):  
T. Herrmann ◽  
D. Jaeger ◽  
W. Stremmel ◽  
C. Herrmann
Keyword(s):  
Pancreatic Cancer ◽  
Disease Progression ◽  
Stable Disease ◽  
Partial Remission ◽  
Advanced Pancreatic Cancer ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Chemotherapy ◽  
Line Chemotherapy

15187 Background: Patients with advanced pancreatic cancer profit from palliative chemotherapy. The role of second-line chemotherapy is not yet established. Methods: We performed a retrospective analysis in 98 patients who were treated at our department from 1/2004–6/2006 due to locally advanced or metastatic adenocarcinoma of the pancreas. Results: At the time of analysis 67 patients had died (median overall survival 9 months), 31 patients are still alive (median follow up 9 months). 12 patients were initially treated with radiochemotherapy. 86 patients received systemic chemotherapy; 43 of these patients were treated with second-line chemotherapy after disease progression. OS was significantly longer in patients who received second-line chemotherapy (10 months versus 5.0 months, p=0.023). Response to second-line chemotherapy was partial remission in 2 patients (4.6 %), stable disease in 18 patients (44.8 %), and progressive disease in 19 patients (44.2 %), in 3 patients the treatment was stopped due to toxicity (6.9 %). 12 patients received second-line treatment after early disease progression under first-line chemotherapy. 9 of these patients did not respond to second-line treatment, 2 achieved stable disease and 1 patient had partial remission. Elevated LDH and CA19.9 serum levels at the time of diagnosis were identified as negative prognostic factors. Conclusions: Prognosis of patients with advanced pancreatic cancer is still poor. Selected patients may benefit from salvage chemotherapy after failure of first-line chemotherapy. No significant financial relationships to disclose.

Impact of first-line cisplatin versus non-cisplatin based chemotherapy on progression-free survival in patients with advanced urothelial carcinoma previously treated with perioperative cisplatin based chemotherapy.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 335-335
Author(s):  
Jennifer A Locke ◽  
Gregory Russell Pond ◽  
Guru Sonpavde ◽  
Andrea Necchi ◽  
Patrizia Giannatempo ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Free Survival ◽  
Ecog Ps ◽  
Line Chemotherapy ◽  
First Line Treatment

335 Background: Perioperative cisplatin based chemotherapy (PCBC) is a standard of care in the management of muscle invasive urothelial carcinoma (UC). Cisplatin based (C) therapy also represents the historical first line treatment of metastatic disease. There is however no data to guide the optimal choice of first line chemotherapy regimen – C re-treatment vs other second-line or non cisplatin regimens (NC) –in UC patients who relapse after receiving PCBC. This multicenter retrospective study compares C vs NC first line treatment on progression-free survival (PFS) for patients (pts) with advanced UC after PCBC and cystectomy. Methods: Data were collected for patients who received various first-line chemotherapies for advanced UC following previous PCBC therapy. Cox proportional hazards models were used to investigate the prognostic ability of type of peri-operative / first-line chemotherapy, visceral metastasis, ECOG status, time from prior chemotherapy (TFPC), anemia, leukocytosis and albumin on PFS. Results: Data were available for 145 pts from 12 centers. The mean age was 62 years, 113 (77.9%) were men and ECOG-PS was 0 or >0 in 74 (51.0%) and 61 (42.0%) patients. Ninety-one (62.8%) pts received C first line, the median number of cycles was 4 (range 1-17) and the median TFPC was 6.2 months (range 1-154). Median overall survival was 86 weeks (95% CI 70-106) and median PFS was 24 (95% CI 18-27) weeks. Time from perioperative chemotherapy (TFPC) (>52 weeks vs ≤52 weeks; HR 0.63 p=0.027) and ECOG-PS at first line (1+ vs 0; HR 1.73 p=0.010), were prognostic of PFS. No significant effect was noted for C vs NC first line (p=0.70); however, among patients with TFPC >52 weeks, patients with NC had worse PFS (median 4.6 months, 95% CI 1.8-12.2) than those who received C (median 8.1, 95% CI 3.2-16.3). Conclusions: There is no evidence to suggest overall superiority of C vs NC based first line chemotherapy or a second-line regimen in patients with advanced UC who received prior PCBC. However, those with TFPC >52 weeks should probably receive C first line chemotherapy given better PFS with C.

Survival benefit of second-line chemotherapy in advanced pancreatic adenocarcinoma: A systematic review of the literature.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 296-296 ◽  
Author(s):  
Adnan Nagrial ◽  
Venessa T. Chin ◽  
Katrin Sjoquist ◽  
Lorraine A. Chantrill ◽  
Desmond Yip
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Single Agent ◽  
Advanced Pancreatic Cancer ◽  
Response Rates ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Chemotherapy ◽  
Line Chemotherapy

296 Background: There is currently no standard of care for the second-line treatment of advanced pancreatic cancer. Very few randomised studies have been performed in this setting. The aim of this analysis was to compare the different therapeutic approaches in this setting, and the rate of second line treatment delivery and its influence on reported overall survival. Methods: We carried out a systematic analysis of studies in advanced pancreatic cancer. 1st and 2nd line chemotherapy trials were identified from MEDLINE, EMBASE & CENTRAL using the COCHRANE sensitive search strategy. Objective response rates (ORR) and survival (PFS & OS) were extracted and compared amongst groups using the Mann-Whitney U test. For 1st line studies, the percentage of patients who received 2nd line chemotherapy was also extracted and plotted against reported median overall survival (OS) and post-progression survival (PPS), defined as arithmetic difference between median OS and progression-free survival. Linear regression was used to explore the relationship between overall survival and second-line chemotherapy. Results: 20 first line clinical trials with 42 treatment arms met the inclusion criteria treating an aggregate total of 5,768 patients. Overall survival was positively correlated with use of second-line chemotherapy (r=0.65; p=0.012). 61 second-line studies were identified treating an aggregate total of 2,562 patients in 66 treatment arms. Combination treatment was associated with an improved response rate (p=0.045) and PFS (p=0.024) when compared to single agent therapy. Conclusions: In this exploratory analysis, these data suggest that there is a small benefit of second-line chemotherapy in pancreatic cancer. In first-line chemotherapy studies, the use of subsequent treatment correlates with improved overall survival. In second line studies, combination chemotherapy is associated with higher response rates and survival.

Beneficial trends of second-line chemotherapy in advanced pancreatic cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14680-e14680
Author(s):  
Milton Jose B. Silva ◽  
Joyce Maria L. Maia ◽  
Adriana Regina G. Ribeiro ◽  
Ludmilla T. D. Chinen ◽  
Tadeu Ferreira Paiva Jr ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Advanced Pancreatic Cancer ◽  
Control Analysis ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Chemotherapy ◽  
Kaplan Meier ◽  
Line Chemotherapy

e14680 Background: Despite the lack of high-quality clinical trial data suggesting that second-line chemotherapy (SLC) may affect survival on metastatic pancreatic cancer (mPC), most of centers utilizes them after the failure of initial treatment in patients who maintain a good performance status. The aim of the present study was to review our institutional experience with SLC and estimate its role in overall survival (OS). Methods: We performed a retrospective matched case-control analysis based on search of medical records in 106 consecutive patients with mPC at our institution. Patients received first line chemotherapy (FLC) and SLC (n = 49) or FLC only (n =57) from September 2005 to December 2010. Case matching was performed with respect to age (< 60y versus ≥ 60y), topography (head of the pancreas versus body or tail), sites of metastasis. Overall survival was analyzed by Kaplan-Meier method. Results: Median age was 63 (32-86) and 60 (38-85) for SLC group and FLC group respectively. There was no significant difference between the two groups regarding topography, TNM stage at diagnosis, and sites of metastasis. The main site of metastasis was the liver (24,4%), followed by peritoneum (2,8%).Median follow-up of both groups was 8.4 months (0.23m-54.93m). First line treatment consisted of Gemcitabine (55.1% x 49.1%) and gemcitabine + cisplatin (18.4%x14%) in SLC and FLC group respectively. The most used second line treatment was Capecitabine (32.7%), followed by Folfox (16.3%), and Fluoracil (10.2%). The Kaplan-Meier estimate of the overall median survival, 1-year and 2-years survival rate was 15.72 months versus 7.2 months (p:0.021), and 60% vs. 32%, and 30% vs. 19% in SLC and FLC group, respectively. Conclusions: Our result suggests that second-line chemotherapy may be beneficial to improve overall survival in patients with advanced pancreatic cancer. It’s important that new and ongoing clinical trials clarify which is the best chemotherapy scheme in this setting.

scholarly journals TheraSphere Yttrium-90 Glass Microspheres Combined With Chemotherapy Versus Chemotherapy Alone in Second-Line Treatment of Patients With Metastatic Colorectal Carcinoma of the Liver: Protocol for the EPOCH Phase 3 Randomized Clinical Trial (Preprint)

2018 ◽  
Author(s):  
Nikhil Chauhan ◽  
Mary F Mulcahy ◽  
Riad Salem ◽  
Al B Benson III ◽  
Eveline Boucher ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Progression ◽  
Progression Free Survival ◽  
Control Group ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Phase 3 ◽  
Free Survival ◽  
Line Chemotherapy

BACKGROUND Colorectal cancer is one of the most common cancers and causes of cancer-related death. Up to approximately 70% of patients with metastatic colorectal cancer (mCRC) have metastases to the liver at initial diagnosis. Second-line systemic treatment in mCRC can prolong survival after development of disease progression during or after first-line treatment and in those who are intolerant to first-line treatment. OBJECTIVE The objective of this study is to evaluate the efficacy and safety of transarterial radioembolization (TARE) with TheraSphere yttrium-90 (90Y) glass microspheres combined with second-line therapy in patients with mCRC of the liver who had disease progression during or after first-line chemotherapy. METHODS EPOCH is an open-label, prospective, multicenter, randomized, phase 3 trial being conducted at up to 100 sites in the United States, Canada, Europe, and Asia. Eligible patients have mCRC of the liver and disease progression after first-line chemotherapy with either an oxaliplatin-based or irinotecan-based regimen and are eligible for second-line chemotherapy with the alternate regimen. Patients were randomized 1:1 to the TARE group (chemotherapy with TARE in place of the second chemotherapy infusion and subsequent resumption of chemotherapy) or the control group (chemotherapy alone). The addition of targeted agents is permitted. The primary end points are progression-free survival and hepatic progression-free survival. The study objective will be considered achieved if at least one primary end point is statistically significant. Secondary end points are overall survival, time to symptomatic progression defined as Eastern Cooperative Oncology Group Performance Status score of 2 or higher, objective response rate, disease control rate, quality-of-life assessment by the Functional Assessment of Cancer Therapy-Colorectal Cancer questionnaire, and adverse events. The study is an adaptive trial, comprising a group sequential design with 2 interim analyses with a planned maximum of 420 patients. The study is designed to detect a 2.5-month increase in median progression-free survival, from 6 months in the control group to 8.5 months in the TARE group (hazard ratio [HR] 0.71), and a 3.5-month increase in median hepatic progression-free survival time, from 6.5 months in the control group to 10 months in the TARE group (HR 0.65). On the basis of simulations, the power to detect the target difference in either progression-free survival or hepatic progression-free survival is >90%, and the power to detect the target difference in each end point alone is >80%. RESULTS Patient enrollment ended in October 2018. The first interim analysis in June 2018 resulted in continuation of the study without any changes. CONCLUSIONS The EPOCH study may contribute toward the establishment of the role of combination therapy with TARE and oxaliplatin- or irinotecan-based chemotherapy in the second-line treatment of mCRC of the liver. CLINICALTRIAL ClinicalTrials.gov NCT01483027; https://clinicaltrials.gov/ct2/show/NCT01483027 (Archived by WebCite at http://www.webcitation.org/734A6PAYW) INTERNATIONAL REGISTERED REPOR RR1-10.2196/11545

Sign in / Sign up

Export Citation Format

Share Document