Author(s): Emma Sophia Zwanenburg, MD1,2; Charlotte El Klaver, MD, PhD1,2; Daniel D. Wisselink, MD1,2; Cornelis J.A. Punt, MD, PhD3; P. Snaebjornsson, MD, PhD4,5; Johannes Crezee, MD, PhD2,6; Arend G.J. Aalbers, MD, PhD1; Alexandra R.M. Brandt-Kerkhof, MD7; Andre J.A. Bremers, MD, PhD8; Pim J.W.A. Burger, MD, PhD9; Hans F.J. Fabry, MD10; Floris T.J. Ferenschild, MD, PhD11; Sebastiaan Festen, MD, PhD12; Wilhemina M.U. van Grevenstein, MD, PhD13; Patrick H.J. Hemmer, MD, PhD14; Ignace H.J.T. de Hingh, MD, PhD8; Niels F.M. Kok, MD, PhD9; M. Kusters, MD, PhD1,2; G.D. Musters, MD, PhD1,2; Lotte Schoonderwoerd, MD10; J.B. Tuynman, MD, PhD2,11; Anthony W.H. van de Ven, MD, PhD12; Henderik L. van Westreenen, MD, PhD13; M.J. Wiezer, MD, PhD14; David D.E. Zimmerman, MD, PhD15; Annette van Zweeden, MD16; Marcel G.W. Dijkgraaf, MD, PhD17,18; Pieter J. Tanis, MD, PhD1,2,7
ABSTRACT
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.
Whether adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) might prevent peritoneal metastases after curative surgery for high-risk colon cancer is an ongoing debate. This study aimed to determine 5-year oncologic outcomes of the randomized multicenter COLOPEC trial, which included patients with clinical or pathologic T4N0-2M0 or perforated colon cancer and randomly assigned (1:1) to either adjuvant systemic chemotherapy and HIPEC (n = 100) or adjuvant systemic chemotherapy alone (n = 102). HIPEC was performed using a one-time administration of oxaliplatin (460 mg/m2, 30 minutes, 42°C, concurrent fluorouracil/leucovorin intravenously), either simultaneously (9%) or within 5-8 weeks (91%) after primary tumor resection. Outcomes were analyzed according to the intention-to-treat principle. Long-term data were available of all 202 patients included in the COLOPEC trial, with a median follow-up of 59 months (IQR, 54.5-64.5). No significant difference was found in 5-year overall survival rate between patients assigned to adjuvant HIPEC followed by systemic chemotherapy or only adjuvant systemic chemotherapy (69.6% v 70.9%, log-rank; P = .692). Five-year peritoneal metastases rates were 63.9% and 63.2% (P = .907) and 5-year disease-free survival was 55.7% and 52.3% (log-rank; P = .875), respectively. No differences in quality-of-life outcomes were found. Our findings implicate that adjuvant HIPEC should still be performed in trial setting only.
Author Affiliations
1Amsterdam UMC Location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands; 2Cancer Center Amsterdam, Treatment and Quality of Life, Amsterdam, the Netherlands; 3UMC Utrecht, Department of Epidemiology, Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands; 4Netherlands Cancer Institute, Department of Pathology, Amsterdam, the Netherlands; 5Faculty of Medicine, University of Iceland, Reykjavik, Iceland; 6Amsterdam UMC Location University of Amsterdam, Department of Radiation Oncology, Amsterdam, the Netherlands; 7Erasmus Medical Center, Department of Oncological and Gastrointestinal Surgery, Rotterdam, the Netherlands; 8Radboud University Medical Center, Department of Surgery, Nijmegen, the Netherlands; 9Catharina Hospital, Department of Surgery, Eindhoven, the Netherlands; 10Bravis Hospital, Department of Surgery, Roosendaal, the Netherlands; 11Maashospital Pantein, Department of Surgery, Beugen, the Netherlands; 12Department of Surgery, Onze Lieve Vrouwen Gasthuis, Amsterdam, the Netherlands; 13University Medical Center Utrecht, Department of Surgery, Utrecht, the Netherlands; 14University Medical Center Groningen, Department of Surgery, Groningen, the Netherlands; 9Netherlands Cancer Institute, Department of Surgery, Amsterdam, the Netherlands; 10Bernhoven Hospital, Department of Surgery, Uden, the Netherlands; 11Amsterdam UMC Location Free University, Department of Surgery, Amsterdam, the Netherlands; 12Flevo Hospital, Department of Surgery, Almere, the Netherlands; 13Isala Hospital, Department of Surgery, Zwolle, the Netherlands; 14St Antonius Hospital, Department of Surgery, Nieuwegein, the Netherlands; 15Elisabeth-Tweesteden Hospital, Department of Surgery, Tilburg, the Netherlands; 16Amstelland Hospital, Department of Internal Medicine, Amstelveen, the Netherlands; 17Amsterdam UMC Location University of Amsterdam, Department of Epidemiology and Data Science, Amsterdam, the Netherlands; 18Amsterdam Public Health, Methodology, Amsterdam, the Netherlands
