Sequential FOLFIRI.3 + Gemcitabine Improves Health-Related Quality of Life Deterioration-Free Survival of Patients with Metastatic Pancreatic Adenocarcinoma: A Randomized Phase II Trial

<div><p>Background</p><p>A randomized multicenter phase II trial was conducted to assess the sequential treatment strategy using FOLFIRI.3 and gemcitabine alternately (Arm 2) compared to gemcitabine alone (Arm 1) in patients with metastatic non pre-treated pancreatic adenocarcinoma. The primary endpoint was the progression-free survival (PFS) rate at 6 months. It concludes that the sequential treatment strategy appears to be feasible and effective with a PFS rate of 43.5% in Arm 2 at 6 months (26.1% in Arm 1). This paper reports the results of the longitudinal analysis of the health-related quality of life (HRQoL) as a secondary endpoint of this study.</p><p>Methods</p><p>HRQoL was evaluated using the EORTC QLQ-C30 at baseline and every two months until the end of the study or death. HRQoL deterioration-free survival (QFS) was defined as the time from randomization to a first significant deterioration as compared to the baseline score with no further significant improvement, or death. A propensity score was estimated comparing characteristics of partial and complete responders. Analyses were repeated with inverse probability weighting method using the propensity score. Multivariate Cox regression analyses were performed to identify independent factors influencing QFS.</p><p>Results</p><p>98 patients were included between 2007 and 2011. Adjusting on the propensity score, patients of Arm 2 presented a longer QFS of Global Health Status (Hazard Ratio: 0.52 [0.31-0.85]), emotional functioning (0.35 [0.21–0.59]) and pain (0.50 [0.31 – 0.81]) than those of Arm 1.</p><p>Conclusion</p><p>Patients of Arm 2 presented a better HRQoL with a longer QFS than those of Arm 1. Moreover, the propensity score method allows to take into account the missing data depending on patients’ characteristics.</p><p>Trial registration information</p><p>Eudract N° <a href="https://www.clinicaltrialsregister.eu/ctr-search/trial/2006-005703-34/FR" target="_blank">2006-005703-34</a>. (Name of the Trial: FIRGEM).</p></div

Kaplan-Meier survival curves of the HRQoL deterioration-free survival by treatment arm for the raw and the weighted analysis.

<p>Arm 1: gemcitabine alone, Arm 2: gemcitabine + FOLFIRI.3.</p

Proportion of complete, partial and non responders for HRQoL assessment in each treatment arm.

<p>Proportion of complete, partial and non responders for HRQoL assessment in each treatment arm.</p

Additional file 3: Figure S2. of Additive value of pre-operative and one-month post-operative lymphocyte count for death-risk stratification in patients with resectable pancreatic cancer: a multicentric study

Calibration plots at 48 months for the final multivariate model. Vertical axis is the observed proportion of patients surviving at time of interest. Grey line represents a perfectly calibrated model. Solid line is current prediction model performance with 95 % confidence intervals using bootstrap resampling procedure. (PDF 146 kb

Additional file 2: Table S1. of Additive value of pre-operative and one-month post-operative lymphocyte count for death-risk stratification in patients with resectable pancreatic cancer: a multicentric study

Separate multivariate cox-analysis. (PDF 290 kb

Additional file 1: Figure S1. of Additive value of pre-operative and one-month post-operative lymphocyte count for death-risk stratification in patients with resectable pancreatic cancer: a multicentric study

Overall survival according to cohort set. (PDF 85 kb

Median overall survival according to different criteria.

<p>Median overall survival according to different criteria.</p

Consort flowchart of the primary objective in the FFCD-1004 clinical trial.

<p>Consort flowchart of the primary objective in the FFCD-1004 clinical trial.</p

Pharmacokinetics profiles of gemcitabine (A) and its metabolite (B) overtime during the first round of gemcitabine administration in pancreatic adenocarcinoma cancer patients.

<p>Patients have been sampled before infusion, at the end, and 90 and 120 minutes after ending the infusion. A wide inter-individual variability is observed, either for gemcitabine or for dFdU.</p

Boxplots of CDA activity in prospective compared to retrospective study.

<p>CDAretro stands for CDA activity in gemcitabine-treated patients for various types of cancers in the retrospective study. The boxplot in the middle represents CDA activity in the subgroup of gemcitabine-monotherapy patients in the retrospective study. CDA activities of patients from the prospective study are represented in the boxplot on the right. Isolating gemcitabine-monotherapy treated patients leads to a smoothing effect in CDA activity variability.</p