Prophylactic hyperthermic intraperitoneal chemotherapy in gastric cancer management: short- and long-term outcomes of a prospective randomized study

Abstract

Introduction. Assessment of toxicity and long-term results of hyperthermic intraperitoneal chemotherapy (HIPEC) treatment administered to patients with resectable serosa-invasive gastric cancers. Material and methods. The study was carried out in 2008–2016 and is based on the results of the treatment of 154 gastric cancer patients (stage IIB–IIIC, III–IV Borrmann type) who were randomly assigned to two groups. 76 patients underwent HIPEC combined with radical gastrectomy (HIPEC group) and 78 patients underwent radical gastrectomy without HIPEC (control group). HIPEC was administered after alimentary tract reconstruction and wound closure and comprised 5–6 L of Ringer’s solution (cisplatin 50 mg/m2 + doxorubicin 50 mg/m2) infused at an inflow temperature of 42°C for 1 hour. Results. Although the total number of complications was higher in the HIPEC group than in the control group the difference was statistically insignificant — 20 (26.3%) and 12 (15.3%), respectively (p = 0.141). Surgery-related complications in the HIPEC and control groups were observed in 9 and 5 cases, respectively (p = 0.372). Non-surgical complications were recorded in 11 and 7 cases, respectively (p = 0.435). Overall, the proposed HIPEC regimen administered in combination with radical surgery demonstrated satisfactory patient tolerability. The frequency of grade III toxic reactions according to CTCAE version 5.0 was 9.2%, no grade IV–V toxicities were registered at that. These satisfactory short-term results were followed up with fairly good long-term treatment outcomes. There was an increase in 5-year progression-free survival (42.1 ± 6.3% vs. 16.3 ± 5.5%, p < 0.001) and in dissemination-free survival (45.2 ± 6.3% vs. 19.4 ± 5.9%, p = 0.001) in the HIPEC group vs. the control group with a trend toward improving cancer-specific survival (CSS) in the HIPEC-treated patients [45.1.0 ± 6.4% vs. 27.0 ± 6.7% (p = 0.050)]. Conclusions. While substantially improving long-term GC therapeutic effect, the proposed HIPEC regimen using cisplatin 50 mg/m2 in combination with doxorubicin 50 mg/m2 made it possible to minimize complications (frequency of 26.3%) and toxic reactions [the frequency of grade III toxic reactions was 9.2% (CTCAE, version 5.0)].