Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy improves survival of gastric cancer with peritoneal carcinomatosis: evidence from an experimental study

Abstract

BackgroundCytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) has been considered as a promising treatment modality for gastric cancer with peritoneal carcinomatosis (PC). However, there have also been many debates regarding the efficacy and safety of this new approach. Results from experimental animal model study could help provide reliable information. This study was to investigate the safety and efficacy of CRS + HIPEC to treat gastric cancer with PC in a rabbit model.MethodsVX2 tumor cells were injected into the gastric submucosa of 42 male New Zealand rabbits using a laparotomic implantation technique, to construct rabbit model of gastric cancer with PC. The rabbits were randomized into control group (n = 14), CRS alone group (n = 14) and CRS + HIPEC group (n = 14). The control group was observed for natural course of disease progression. Treatments were started on day 9 after tumor cells inoculation, including maximal removal of tumor nodules in CRS alone group, and maximal CRS plus heperthermic intraperitoneal chemoperfusion with docetaxel (10 mg/rabbit) and carboplatin (40 mg/rabbit) at 42.0 ± 0.5°C for 30 min in CRS + HIPEC group. The primary endpoint was overall survival (OS). The secondary endpoints were body weight, biochemistry, major organ functions and serious adverse events (SAE).ResultsRabbit model of gastric cancer with PC was successfully established in all animals. The clinicopathological features of the model were similar to human gastric PC. The median OS was 24.0 d (95% confidence interval 21.8 - 26.2 d ) in the control group, 25.0 d (95% CI 21.3 - 28.7 d ) in CRS group, and 40.0 d (95% CI 34.6 - 45.4 d ) in CRS + HIPEC group (P = 0.00, log rank test). Compared with CRS only or control group, CRS + HIPEC could extend the OS by at least 15 d (60%). At the baseline, on the day of surgery and on day 8 after surgery, the peripheral blood cells counts, liver and kidney functions, and biochemistry parameters were all comparable. SAE occurred in 0 animal in control group, 2 animals in CRS alone group including 1 animal death due to anesthesia overdose and another death due to postoperative hemorrhage, and 3 animals in CRS + HIPEC group including 1 animal death due to anesthesia overdose, and 2 animal deaths due to diarrhea 23 and 27 d after operation.ConclusionsIn this rabbit model of gastric cancer with PC, CRS alone could not bring benefit while CRS + HIPEC with docetaxel and carboplatin could significantly prolong the survival with acceptable safety.

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from colorectal cancer: A case‐control study from a Chinese center

“…The most important finding was that the median OS could be extended from 8.5 months in Control group to 13.7 months in Study group, with survival prolong rate (SPR) of 61.2%. This improvement is comparable with both experimental studies (23 vs. 40 days, SPR 60% ; 43 vs. 75 days, SPR 74% ) and clinical studies by Yang et al (6.5 vs. 11.0 months, SPR 69%), Verwaal et al (12.6 vs. 22.3 months, SPR 77%), Elias et al (23.9 vs. 62.7 months, SPR 162%), and Cashin et al (23.9 vs. 36.5 months, SPR 53%). Although this is not a strictly randomized study, and the two groups were different in terms of operation complexities, as the HIPEC group had more abdominal areas resection than the control group and thus longer operation time, there was no major selection bias in this study that could account for such big differences in OS.…”

Acetic acid induces cell death: An in vitro study using normal rat gastric mucosal cell line and rat and human gastric cancer and mesothelioma cell lines

“…The present study provides further evidence to support this idea. Moreover, we may suggest using an intraperitoneal application of acetic acid (but not ethanol) alone or in combination with intraperitoneal chemotherapy for treatment of peritoneal cancer . In the future, it will be of interest to test this idea in proper animal models by combining acetic acid with cisplatin, mitomycin‐C, 5‐FU, leucovorin, paclitaxel, S‐1, doxorubicin, and irinotecan …”

Current perspectives on hyperthermic intraperitoneal chemotherapy in gastric cancer

“…This study also showed that PDOX and HIPEC had a much more tolerable side-effect profile than the doxorubicin treatments. 68 Similarly, in another study, Tang et al 69 found that CRS-HIPEC could increase the survival of their diseased rabbits by 60%. Moreover, based on peripheral blood cell counts, liver function, kidney function, and blood chemistries, the side effects were comparable between the control group and the CRS-HIPEC group.…”