RESUMO
BACKGROUND: Metastatic pancreatic adenocarcinoma (MPA) represents a highly lethal condition. Despite the improvements seen with FOLFIRINOX, there is no randomized data to guide treatment selection beyond this regimen. We aimed to evaluate the outcomes of patients with MPA progressing on FOLFIRINOX who were treated with Gemcitabine-based chemotherapy afterwards. METHODS: We included patients aged 18 years or older, treated for MPA with FOLFIRINOX in the first-line setting and who experienced disease progression, with Eastern Cooperative Oncology Group (ECOG) performance status 0-2, and treated with at least one cycle of Gemcitabine-based chemotherapy in second or further lines of treatment. We used descriptive statistics to characterize the study population and Cox proportional-hazards models to describe factors associated with survival. As an exploratory analysis, we compared the outcomes of patients treated with single-agent Gemcitabine with those of patients undergoing Gemcitabine-based polychemotherapy. RESULTS: The study population consisted of 42 patients. Median age was 59 years and 78.6% of patients presented ECOG 0-1. Thirty-three patients (78.6%) were treated with Gemcitabine-based chemotherapy in the second-line setting and 27 patients (64.3%) were treated with single-agent Gemcitabine. Objective response rate and disease control rate were 2.4% and 33.4%, respectively. Median progression-free survival (PFS) and median overall survival (OS) were 2.9 and 5.5 months, respectively. Six-month PFS and OS rates were 19.2% and 46.2%, respectively. We observed no significant difference in OS according to the type of Gemcitabine-based chemotherapy, despite numerically improved disease control rate and PFS for those treated with Gemcitabine-based polychemotherapy. In multivariate analysis, ECOG 2 (vs. ECOG 0-1) was the only factor significantly associated with inferior PFS and OS. CONCLUSIONS: a subgroup of patients with MPA derives benefit from treatment with Gemcitabine-based regimens after FOLFIRINOX. There is a suggestion that Gemcitabine-based combinations, in particular Gemcitabine plus Nab-Paclitaxel, provide superior outcomes compared to single-agent Gemcitabine. Additionally, treatment in this setting should be offered carefully to patients with ECOG 2, as they present shorter survival and increased risk of toxicity.
RESUMO
BACKGROUND: FOLFIRINOX stands a major breakthrough in the management of metastatic pancreatic adenocarcinoma (MPA). Nonetheless, significant side-effects have been reported using standard FOLFIRINOX. We aimed to compare survival outcomes, response rates and toxicity of patients treated with standard or modified FOLFIRINOX in MPA. METHODS: We included patients aged ≥18 years old, with pathologically confirmed MPA, treated with FOLFIRINOX in the first-line setting. Patients submitted to at least one cycle of full-dose FOLFIRINOX were grouped in the standard FOLFIRINOX group. RESULTS: Patients treated with standard FOLFIRINOX were younger and had less comorbidity. We observed no differences in overall survival or in progression-free survival between the two treatment arms. The only variable independently associated with OS was log10[neutrophil-to-lymphocyte ratio (NLR)]. Modified FOLFIRINOX was associated with a lower dose reduction rate, but a slightly increased incidence of severe toxicity. CONCLUSIONS: Modified FOLFIRINOX presents the same activity against MPA as standard FOLFIRINOX. We found no significant differences in toxicity, possibly due to patient selection and a higher dose reduction rate in the standard FOLFIRINOX arm. NLR stood as an important prognostic marker and further research is needed to comprehend its biological meaning in pancreatic cancer.
