Elsevier

European Journal of Cancer

Volume 46, Issue 15, October 2010, Pages 2753-2762
European Journal of Cancer

Time until definitive quality of life score deterioration as a means of longitudinal analysis for treatment trials in patients with metastatic pancreatic adenocarcinoma

https://doi.org/10.1016/j.ejca.2010.07.023Get rights and content

Abstract

Background

The Fédération Francophone de Cancérologie Digestive phase III trial in patients with metastatic pancreatic adenocarcinoma comparing 5FU, folinic acid and cisplatin combination followed by gemcitabine (Arm A) versus the opposite sequence (Arm B) failed to demonstrate a benefit in overall survival. To longitudinally compare the quality of life (QoL) we explored different definitions of time until definitive deterioration (TUDD) of QoL scores according to minimal clinically important difference (MCID) cut-offs.

Methods

QoL was evaluated using the EORTC QLQ-C30 every 8 weeks until death. The following scores were analysed: global health, emotional functioning, physical functioning, fatigue and pain. TUDD was defined as the time interval between randomisation and the first occurrence of a decrease in QLQ-C30 score ⩾5 points without any further improvement in QoL score ⩾5 points or any further available QoL data. Analyses were repeated using a 10 point MCID and/or including death as event.

Results

From 08/2003 to 05/2006, 102 patients in Arm A and 100 in Arm B were included. Using a 5 and a 10 point MCID, TUDD curves of the 5 scores did not differ according to treatment arm., The median TUDD of global health was 5.2 months (4.3–6.2) in Arm A and 6.1 months (5.1–8.5) in Arm B (log-rank p = 0.50) including death as an event for a 5 point MCID. Multivariate Cox model showed that tumour localisation and progression were independently associated with TUDD (p < 0.05).

Conclusions

The strategy of chemotherapy did not influence the deterioration of QoL. The TUDD approach seems to provide meaningful clinical results that are adapted to metastatic pancreatic adenocarcinoma trials.

Introduction

Pancreatic adenocarcinoma is the fifth cause of death from cancer in Western countries with less than 5% of patients still living at 5 years.1 Gemcitabine-based chemotherapy is the gold standard for the systemic treatment of advanced pancreatic cancer2 with a 5.6 month median overall survival (OS). Others trials with new therapeutic protocols3, 4, 5, 6, 7, 8 have failed to demonstrate any benefit in OS and one study has showed a modest but significant increase in OS when gemcitabine is combined with erlotinib.9 The 5FU, folinic acid and cisplatin combination (LV5FU2-P) is an alternative option but the optimal order of the regimens needed be evaluated. The Fédération Francophone de Cancérologie Digestive no. 0301 phase III trial was performed to compare LV5FU2-P followed by gemcitabine versus gemcitabine followed by LV5FU2-P. This trial did not show any benefit in survival whatever the sequence administration.10 The Food and Drug Administration reported that QoL is the main outcome to judge efficacy of treatment modalities when no OS differences are demonstrated.11, 12, 13, 14, 15 Furthermore, because of the poor prognosis of advanced pancreatic cancer and the symptom burden, palliation and finding a balance between health-related quality of life (QoL) and OS in these therapeutic strategies is of paramount importance. Based on these therapeutic goals, Burris et al.2 used clinical benefit (definition based on pain and performance status) as the primary aim of the phase III trial to show that gemcitabine first-line therapy was the gold standard.

The primary aim of this study was to longitudinally compare QoL according to treatment sequence of the FFCD 0301 trial The secondary aim was to explore definitions of ‘time until definitive deterioration’ (TUDD) in the QoL score according to the ‘minimal clinically important difference’ (MCID) cut-off.

Section snippets

Method

The design of this study has been described in detail elsewhere.10

Metastatic pancreatic adenocarcinoma (MPA) patients with WHO performance status (PS) ⩽2 and a life expectancy >2 months were randomised 1:1 (minimisation) between Arm A, LV5FU2-cisplatin followed by gemcitabine after progression and Arm B gemcitabine followed by LV5FU-cisplatin after progression. Patients were stratified according to WHO PS (0, 1 versus 2), tumour localisation (head versus other) and participating institutions

Population

Between August 2003 and May 2006, 102 patients were included in Arm A (LV5FU2-cisplatin first line) and 100 patients were included in Arm B (Gemcitabine first line) with a median follow-up of 44 months (Fig. 1).

According to treatment arm patient characteristics were well balanced, details had been presented elsewhere.10

QoL scores at baseline and completion

As shown in Fig. 2, 179 patients (88.61%) completed the QoL questionnaire at baseline, 114 at the 1st follow-up, 83 at the 2nd and 57 at the 3rd. Age, sex, prior treatments, as

Discussion

Studies have shown that most oncologists or patients are unwilling to prolong survival at the expense of worsening QoL.25, 26 From this point of view, the results of QoL as a secondary end-point in the FFCD trial10 are important to analyse the impact of sequence line administration. Our study shows that LV5FU2-P followed by gemcitabine or the opposite sequence did not significantly influence longitudinal QoL in patients with MPA. Progression and tumour localisation other than in the head of the

Contributorship statement

Study concepts: F. Bonnetain, L. Dahan, J.F. Seitz, L. Bedenne, J.L. Legoux, P. Rougier, P. Hammel, M. Ychou, E. Mitry, B. Chauffert & L. Bedenne.

Study design: F. Bonnetain, L. Dahan, J.F. Seitz, L. Bedenne, J.L. Legoux, P. Rougier, P. Hammel, M. Ychou, E. Mitry, B. Chauffert & L. Bedenne.

Data acquisition: All authors.

Quality control of data and algorithms: F. Bonnetain, Emilie Maillard, L. Dahan & J.F. Seitz.

Data analysis and interpretation: F. Bonnetain, E. Maillard, L. Dahan, J.F. Seitz, P.

Funding

This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Conflict of interest statement

None declared.

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