Fibrin-Sealant-Delivered Cisplatin Chemotherapy Versus Cisplatin Hyperthermic Intraperitoneal Perfusion Chemotherapy for Locally Advanced Gastric Cancer Without Peritoneal Metastases: A Randomized Phase-II Clinical Trial with a 40-Month Follow-up

Abstract

A new intraoperative cisplatin administration method for patients with locally advanced gastric cancer (AGC) and without peritoneal metastasis, fibrin-sealant-delivered cisplatin chemotherapy, was reported, and its safety, pharmacokinetics, and efficacy were compared with cisplatin hyperthermic intraperitoneal perfusion chemotherapy. Forty-two AGC patients were randomly divided into 2 groups: fibrin-sealant-delivered cisplatin chemotherapy (FS) (n = 21) and cisplatin hyperthermic intraperitoneal perfusion chemotherapy (CHIC) (n = 21). Both groups received 120 mg cisplatin after complete cytoreductive surgery. At different time points, cisplatin concentrations in patients' sera and urine samples were measured to determine time-dependent maximal concentration (Cmax) and the area under the curve (AUC). The primary and secondary end-points were overall survival (OS) and safety profiling, respectively. Occurrence of grade-3 to grade-4 liver or kidney dysfunction was less frequent in the FS group than in the CHIC group (28.6 % vs 47.6 %). Cisplatin Cmax and AUC for the serum and urine of the FS patients were significantly lower than that of the CHIC patients. Elimination half-life of cisplatin in the FS group was significantly longer than in the CHIC group (24.1 h vs 14.2 h). After a median follow-up of 40 months, 1-, 2-, and 3-years OS were 90.5 %, 71.4 %, and 61.9 % in the FS group, and 61.9 %, 47.6 %, and 42.8 % in the CHIC group, respectively. The median OS was 35.9 months in the FS group and 29.1 months in the CHIC group. Fibrin-sealant-delivered cisplatin chemotherapy was as effective and had a favorable pharmacokinetic profile with similar survival outcomes as cisplatin hyperthermic intraperitoneal perfusion chemotherapy following complete cytoreductive surgery of locally advanced GC without peritoneal metastases.

The 30-year experience—A meta-analysis of randomised and high-quality non-randomised studies of hyperthermic intraperitoneal chemotherapy in the treatment of gastric cancer

“…The flow diagram in Figure 1 details the selection process. We divided studies into two groups of analysis: treatment of AGC without carcinomatosis (nine RCTs(6, 13–20) and nine NRCTs(6, 23–30)) and treatment of GCPC (two RCTs(21, 22) and twelve NRCTs(24–26, 28–36)). Six authors(24–26, 28–30) of NRCTs reported in the same article both categories with separate analysis.…”

“…In the analysis of AGC without carcinomatosis, we included a total of 1810 patients, 731 undergoing gastrectomy+HIPEC and 1079 standard gastrectomy alone. The nine RCTs(6, 13–20) contributed 970 cases, 404 of them allocated in the HIPEC group. In the GCPC analysis, we included a total of 620 patients, 289 undergoing CRS+HIPEC, while 331 patients served as control cases (244 received cytoreduction surgery and 87 systemic chemotherapy).…”

“…We did not analyze this group because it met the exclusion criteria for the meta-analysis. Eight studies(6, 14–16, 18, 26, 30) reported the use of Mitomycin C (MMC), eight studies(9, 16, 27, 30, 33, 42–44) a combination of MMC with cisplatin 8,12,18,23 or etoposide(25) or cisplatin+etoposide(24, 27, 29), one study(20) cisplatin alone, and another study(19) cisplatin combined with fluorouracil. The studies provided limited data regarding administration of neoadjuvant and adjuvant treatments.…”

Intraperitoneal perfusion chemotherapy and whole abdominal hyperthermia using external radiofrequency following radical D2 resection for treatment of advanced gastric cancer

“…A study by Cui et al found that neoadjuvant chemotherapy along with postoperative IP perfusion chemotherapy with hyperthermia achieved a better progression-free survival (33 vs. 26 months), and overall survival (OS) (36 vs. 27 months) than neoadjuvant chemotherapy alone [15]. In contrast, a study by Huang et al found that adjuvant IP chemotherapy with hyperthermia did not prolong OS (29.1 vs. 35.9 months) compared with chemotherapy alone [16]. A recently published study showed that in ovarian cancer the addition of HIPEC to interval cytoreductive surgery resulted in longer recurrence-free survival and OS than surgery alone and had no higher rates of adverse effects [17].…”

Efficacy and safety of intraperitoneal chemotherapy in patients with advanced gastric cancer: a cumulative meta-analysis of randomized controlled trials

“…However, the treatment effect of IPC in carcinomatosis of gastric origin remains disappointing and inconclusive. Several trials have indicated that IPC may increase survival rate in advanced gastric cancer [ 9 – 15 ], while the results of another trial showed adverse effects on survival rate [ 16 ]. Furthermore, most relevant trials have suggested that IPC has no significant effect on survival rate [ 17 – 31 ].…”