Docetaxel- and 5-FU-concurrent radiotherapy in patients presenting unresectable locally advanced pancreatic cancer: a FNCLCC-ACCORD/0201 randomized phase II trial's pre-planned analysis and case report of a 5.5-year disease-free survival

Lucie Oberic,Frédéric Viret,Charlotte Baey,Patrice Celier,Françoise Mornex,Michel Ducreux,Jaafar Bennouna,Jean-Pierre Pignon,Jocelyne Berille,Antoine Adenis,Marc Ychou,Didier Peiffert

doi:10.1186/1748-717x-6-124

Abstract

BackgroundTo explore possible improvement in the treatment of locally advanced pancreatic carcinoma (LAPC) we performed a randomized, non-comparative phase II study evaluating docetaxel - plus either daily continuous 5 FU or weekly cisplatin concurrent to radiotherapy. We report here the results of the docetaxel plus 5 FU regimen stopped according to the interim analysis. The docetaxel plus cisplatin arm was continued.MethodsForty (40) chemotherapy-naive patients with unresectable LAPC were randomly assigned (1:1) to either continuous fluorouracil (5-FU) 200 mg/m2/day (protracted IV) and docetaxel (DCT) 20 mg/m2/week or DCT 20 mg/m2 and cisplatin (CDDP) 20 mg/m2, plus concurrent radiotherapy for a period of 6 weeks. The radiation dose to the primary tumor was 54 Gy in 30 fractions. The trial's primary endpoint was the 6-month crude non-progression rate (NPR). Secondary endpoints were tolerance, objective response rate, and overall survival. Accrual was to be stopped if at 6 months more than 13 disease progressions were observed in 20 patients.ResultsEighteen (18) progressions occurred at 6 months in the 5-FU-DCT arm. Six-month NPR was 10% (95%CI: 0-23). Six and 12-month survivals were 85% (95%CI: 64-95) and 40% (95%CI: 22-61); median overall survival was 10.1 months. Median progression-free survival was 4.3 months. We report the case of one patient who was amenable to surgery and has been in complete response (CR) for 5.5 years. Toxicities grade ≥ 3 were reported in 75% of patients; no treatment-related death occurred. Severe toxicities were mainly vomiting (35%), abdominal pain (10%) and fatigue (10%).ConclusionsCombination of 5-FU, docetaxel and radiotherapy has inadequate efficacy in the treatment of LAPC despite good tolerance for the 5-FU-DCT regimen.Trial RegistrationClinicalTrials.gov: NCT00112697

Highlights

To explore possible improvement in the treatment of locally advanced pancreatic carcinoma (LAPC) we performed a randomized, non-comparative phase II study evaluating docetaxel - plus either daily continuous 5 FU or weekly cisplatin concurrent to radiotherapy
There is no definite evidence of the superiority of either its tolerance or efficacy compared to bolus 5-FU, continuous 5-FU intravenous infusion, delivered with concurrent radiotherapy (RT), is of common use in the treatment of a number of gastrointestinal cancers including pancreatic and colorectal carcinoma [10,11]
T3 and T4 tumors represented the majority of cases, 40% and 35% respectively

Summary

Introduction

To explore possible improvement in the treatment of locally advanced pancreatic carcinoma (LAPC) we performed a randomized, non-comparative phase II study evaluating docetaxel - plus either daily continuous 5 FU or weekly cisplatin concurrent to radiotherapy. There is no definite evidence of the superiority of either its tolerance or efficacy compared to bolus 5-FU, continuous (protracted) 5-FU intravenous infusion, delivered with concurrent radiotherapy (RT), is of common use in the treatment of a number of gastrointestinal cancers including pancreatic and colorectal carcinoma [10,11]. Docetaxel (DCT) is a semisynthetic taxane with a large spectrum of antitumoral activity including pancreatic cancer [13]. The activity of this drug in first-line metastatic patients has been demonstrated as has its radiosensitizing potential [14,15,16]. Several phase II and phase III trials have shown that the addition of both cisplatin and fluorouracil to docetaxel did not increase toxicity [17]

Methods

Results

Conclusion