Is gemcitabine effective for pancreatic cancer after progression to FOLFIRINOX?

Abstract

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.

Systematic review and meta-analysis of gemcitabine-based chemotherapy after FOLFIRINOX in advanced pancreatic cancer

“…6 journals.sagepub.com/home/tam A total of 11 studies assessed the DCR of gemcitabine-based chemotherapy (412 patient). 12,22,[25][26][27][28][29][30][31][32][33] Radiological response evaluation took place every 8 weeks in four studies 22,26,27,33 and in one study the median time to first disease response assessment was 8.9 weeks. 32 In the remaining investigations, time to first disease response evaluation was not stated.…”

“…12,22,[25][26][27][28][29][30][31][32][33][34][35] Six studies were multicentric investigations 22,23,26,27,31,34 and seven were available solely as posters or electronic abstracts. 11,24,25,[29][30][31]34 S7 illustrates treatment characteristics in the selected studies. Amongst noncomparative studies, five evaluated the activity of single-agent gemcitabine [25][26][27]33,35 and eight assessed the activity of gemcitabine plus nab-paclitaxel.…”

“…11,24,25,[29][30][31]34 S7 illustrates treatment characteristics in the selected studies. Amongst noncomparative studies, five evaluated the activity of single-agent gemcitabine [25][26][27]33,35 and eight assessed the activity of gemcitabine plus nab-paclitaxel. 12,22,[28][29][30][31][32]34 In the three two-arm comparative studies, treatment arms included single-agent gemcitabine and gemcitabine plus nab-paclitaxel.…”

“…Ten studies evaluated the ORR of gemcitabine-based chemotherapy (370 patients). 12,22,[25][26][27][28][29][30][31][32] Seven used RECIST criteria to assess response. 22,[25][26][27][28]31,32 In the remaining studies, the method of response evaluation was not described.…”

“…Seven studies reported data on any grade 3/4 toxicity (275 patients). 12,22,25,27,29,33,34 Toxicity data was collected according to the Common Terminology Criteria for Adverse Events (CTCAE) 4.0 in three studies. 22,27,33 In the remaining investigations reporting any grade 3/4 toxicity data, the criterium used to classify toxicity was not stated.…”