Regional hyperthermia with cisplatin added to gemcitabine versus gemcitabine in patients with resected pancreatic ductal adenocarcinoma: The HEAT randomised clinical trial. (March 2023)

• Record Type: Journal Article
• Authors: Issels, Rolf D.; Boeck, Stefan; Pelzer, Uwe; Mansmann, Ulrich; Ghadjar, Pirus; Lindner, Lars H.; Albertsmeier, Markus; Angele, Martin K.; Schmidt, Michael; Xu, Yujun; Bahra, Marcus; Pratschke, Johann; Schoenberg, Michael; Thasler, Wolfgang E.; Salat, Christoph; Stoetzer, Oliver J.; Knoefel, Wolfram T.; Graf, Dirk; Wessalowski, Rüdiger; Keitel-Anselmino, Verena; Koenigsrainer, Alfred; Bitzer, Michael; Zips, Daniel; Bamberg, Michael; Fietkau, Rainer; Ott, Oliver; Kawecki, Maciej; Wyrwicz, Lucjan; Rutkowski, Piotr; Rentsch, Markus; Ababei, Juliana; Reichardt, Peter; Rigamonti, Marco; Weber, Bernhard; Abdel-Rahman, Sultan; Tschoep–Lechner, Katharina; Jauch, Karl-Walter; Bruns, Christiane J.; Oettle, Helmut; von Bergwelt-Baildon, Michael; Heinemann, Volker; Werner, Jens;
• Is Part Of: European journal of cancer. Volume 181(2023)
• Page Start: 155
• Page End: 165
• Publication Date: 2023-03
• Subjects: Pancreatic cancer -- Adjuvant chemotherapy -- Randomised clinical trial -- Regional hyperthermia -- Cisplatin -- Gemcitabine -- HEAT study; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2022.12.009
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Background: Regional hyperthermia (RHT) with cisplatin added to gemcitabine showed efficacy in gemcitabine-pre-treated patients with advanced pancreatic ductal adenocarcinoma. We conducted a randomised clinical trial to investigate RHT with cisplatin added to gemcitabine (GPH) compared with gemcitabine (G) in the adjuvant setting of resected pancreatic ductal adenocarcinoma. Methods: This randomised, multicentre, open-label trial randomly assigned patients to either GPH (gemcitabine 1000 mg/m 2 on day 1, 15 and cisplatin 25 mg/m 2 with RHT on day 2, 3 and 15, 16) or to G (gemcitabine 1000 mg/m 2 on day 1, 8, 15), four-weekly over six cycles. Disease-free survival (DFS) was the primary end-point. Secondary end-points 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 versus 9.8 months; p = 0.031). Median OS reached 33.2 versus 25.2 months (p = 0.099) with 5-year survival rates of 28.4% versus 18.7%. Excluding eight patients who received additional capecitabine in the G-arm (investigators choice), median OS favoured GPH (p = 0.052). Adverse events CTCAE (Common Terminology Criteria for Adverse Events) grade ≥3 occurred in 61.5% (GPH) versus 63.6% (G) of patients. Two patients in the G-group died because of treatment-related toxic effects. Conclusions: The randomised controlled Hyperthermia European Adjuvant Trial study failed to demonstrate a significant difference in DFS. However, it suggests a difference in post-recurrence survival and a trend for improved OS. ClinicalTrials: gov, number NCT01077427. Highlights: First study in PDAC investigating hyperthermia added to adjuvant chemotherapy. The study failed to improve disease-free survival as the primary endpoint. Post-recurrence survival was improved with a trend of improved overall survival. Toxicity compares favorably with a more intensive adjuvant chemotherapy. The study offers new perspectives to gain perioperative benefit in PDAC.