Regional Hyperthermia with Cisplatin added to Gemcitabine versus Gemcitabine in Patients with Resected Pancreatic Ductal Adenocarcinoma (PDAC): The HEAT Randomized Clinical Trial
Mené sur 117 patients atteints d'un adénocarcinome canalaire du pancréas de stade avancé et réséqué (durée de suivi : 56,6 mois), cet essai randomisé multicentrique évalue l'efficacité, du point de vue de la survie sans maladie, de l'ajout à la gemcitabine d'un traitement combinant hyperthermie régionale et cisplatine
Background: Regional hyperthermia (RHT) with cisplatin added to gemcitabine showed efficacy in gemcitabine-pretreated patients with advanced PDAC. We conducted a randomized clinical trial to investigate RHT with cisplatin added to gemcitabine (GPH) compared with gemcitabine (G) in the adjuvant setting of resected PDAC. Methods: This randomized, multicenter, open-label trial randomly assigned patients to either GPH (gemcitabine 1000 mg/m2 on day 1, 15 and cisplatin 25 mg/m2 with RHT on day 2,3 and 15,16) or to G (gemcitabine 1000 mg/m2 on day 1,8,15), four-weekly over six cycles. Disease-free survival (DFS) was the primary endpoint. Secondary endpoints included overall survival (OS) and safety. Results: A total of 117 eligible patients (median age, 63 years) were randomly allocated to treatment (57 GPH; 60 G). With a follow-up time of 56.6 months, the median DFS was 12.7 compared to 11.2 months for GPH and G, respectively (p=0.394). Median post-recurrence survival was significantly prolonged in the GPH-group (15.3 vs 9.8 months; p=0.031). Median OS reached 33.2 vs 25.2 months (p=0.099) with 5-year survival rates of 28.4% vs 18.7%. Excluding eight patients who received additional capecitabine in the G-arm (investigators choice), median OS favored GPH (p=0.052). Adverse events CTCAE grade ≥3 occurred in 61.5% (GPH) vs 63.6% (G) of patients. Two patients in the G-group died because of treatment-related toxic effects. Conclusions: The randomized controlled HEAT study failed to demonstrate a significant difference in DFS. However, it suggests a difference in post-recurrence survival and a trend for improved OS. Trial Registration ClinicalTrials.gov, number NCT01077427.