Citorreducción y HIPEC versus citorreducción aislada en pacientes con carcinomatosis peritoneal por carcinoma de ovario, trompa de falopio o carcinoma peritoneal primario : resultados del ensayo clínico fase III prospectivo y randomizado CARC INOHIPEC (NCT- 02328716)

Abstract

INTRODUCTION Ovarian cancer is the most lethal gynecological neoplasm and is the most frequent cause of peritoneal carcinomatosis among women. Most patients (75%) are diagnosed in advanced stages of the disease. Cytoreduction procedures (CRS) and administration of hyperthermic intraperitoneal chemotherapy (HIPEC) have shown their efficacy in multiple malignancies and could offer a prognostic benefit also in patients with advanced ovarian cancer. HYPOTHESIS AND OBJECTIVES The hypothesis of the present study was that the administration of HIPEC in patients with peritoneal carcinomatosis of ovarian, tubal or primary peritoneal origin, allows to reduce and delays the appearance of recurrences, thus increasing disease-free survival and overall survival, without cause an increase in postoperative morbidity and mortality or subsequent quality of life. The main objective of this study was to investigate whether the administration of HIPEC with cisplatin 75mg / m2 after complete cytoreduction in these patients increases disease-free survival compared to patients treated with surgery alone. Secondary objectives were to study whether HIPEC also increases overall survival, to analyze the morbidity and mortality derived from these procedures, and their relationship with the administration of intraperitoneal chemotherapy, and to evaluate the influence of CRS and HIPEC on quality of life. PATIENTS AND METHOD A prospective, randomized phase III clinical trial has been conducted in patients diagnosed with carcinomatosis from ovarian, fallopian tube, or primary peritoneal cancer, treated with a minimum of 3 cycles of neoadjuvant chemotherapy (carboplatin and paclitaxel). Between March 2012 and November 2018, 71 patients were randomized to receive cytoreductive surgery alone (control group, 36 patients) or with HIPEC (experimental group, 35 patients), ending follow-up on February 1,2019. RESULTS After a median follow-up of 32 months, 26 patients in the control group (72.2%) and 23 patients in the experimental group (65.7%) had presented a recurrence of the disease at the time of closing the database. The median disease-free survival was 12 months in the control group, and 18 months in the experimental group. After multivariate analysis, HIPEC was found to be an independent protective factor for the development of recurrence (HR = 0.12, 95% CI = 0.02-0.89, p = 0.038). Overall survival presented a favorable trend in the experimental group, although without reaching statistical significance in the univariate and multivariate analysis. Eighteen patients (50%) in the control group, and 16 patients (45.7%) in the experimental group, had died, with a median overall survival of 45 and 52 months, respectively. The complication rate of any grade (I-V) was 58.3% in the control group, and 45.7% in the experimental group (p=N.S.), while the rate of severe complications (III-V) were 27.8% and 25.7% (p=N.S.), with a mortality of 2.8% and 2.9% respectively (p> 0.05). Cytoreduction procedures with or without HIPEC had no impact on the quality of life reflected by the EORTC-Q30-OV 28 and EQ-5D tests. CONCLUSIONS The association of HIPEC after cytoreduction in patients with newly diagnosed peritoneal carcinomatosis from ovarian cancer was associated with a significant increase in disease-free survival, and with a favorable trend in overall survival, without finding differences in postoperative morbidity or mortality, or in the quality of life.