Abstract
Peritoneal metastasis of gastric cancer is mainly caused by the dispersion of free cancer cells from the serosal surface of the invaded stomach, from surgically transected lymphatic channels, and from tumor cell-containing blood from the primary lesion into the peritoneal cavity. Intraperitoneal chemotherapy (IPC) combined with surgery has performed for the prevention and treatment of peritoneal metastasis in gastric cancer. The efficacy of this technique is influenced by the pharmacokinetic advantage achievable with the anticancer drug, timing of administration, combination with hyperthermia, and tumor volume. The pharmacokinetic advantage for peritoneal cavity exposure relative to peripheral circulation by intraperitoneal delivery for drugs including cisplatin (10-fold advantage), mitomycin C (20- to 30-fold advantage), docetaxel (500-fold advantage), and paclitaxel (1000-fold advantage) has been confirmed. To avoid uneven drug distribution in the peritoneal cavity and the re-growth of residual tumor, it seems to be reasonable to perform IPC perioperatively; however, early perioperative intraperitoneal chemotherapy (EPIC) has a relatively high morbidity rate compared with intraoperative IPC. Hyperthermia has both cytotoxicity of itself and a synergistic effect with anticancer drugs, especially mitomycin C. In the adjuvant setting, patients with either hyperthermic intraperitoneal chemotherapy (HIPEC) or EPIC showed a significant improvement of survival compared to those with surgery alone. In addition, extensive intraoperative peritoneal lavage (EIPL) seems also to be a reasonable method to reduce free cancer cells in the peritoneal cavity. For the treatment of peritoneal metastasis, cytoreductive surgery which achieves R0 or R1 resection followed by IPC has demonstrated a survival benefit, whereas gross residual tumor (R2) treated by IPC has shown poor prognosis. Extensive cytoreductive surgery, such as peritonectomy, followed by IPC achieved long-term survival for selected patients, though this aggressive procedure led to high morbidity and mortality rates. It seems that combined chemotherapy (systemically and intraperitoneally) followed by conversion surgery can be expected to be a powerful procedure for the patients with gross peritoneal tumors.
Highlights
One of the most characteristic features of gastric cancer and the most frequent causes of death from this disease is peritoneal metastasis
To avoid uneven drug distribution in the peritoneal cavity and the re-growth of residual tumor, it seems to be reasonable to perform Intraperitoneal chemotherapy (IPC) perioperatively; early perioperative intraperitoneal chemotherapy (EPIC) has a relatively high morbidity rate compared with intraoperative IPC
The treatment of peritoneal metastasis has consisted of systemic chemotherapy with sequential methotrexate (MTX) and 5-FU, or IPC with mitomycin C (MMC), cisplatin, OK432, and other agents
Summary
One of the most characteristic features of gastric cancer and the most frequent causes of death from this disease is peritoneal metastasis. Considering the efficacy and survival benefit of S-1 in patients with peritoneal metastasis, which have been documented by many case reports and other reports [28, 29], it will be necessary to include S-1 in the regimen of a randomized study for treatment of peritoneal metastasis Taxanes such as docetaxel and paclitaxel bind to tubulin, leading to microtubule stabilization, mitotic arrest and, subsequently, cell death [30,31]. The activity of taxanes may depend on the property of killing tumor cells in the absence of wild-type p53 function [32], unlike other drugs requiring wild-type p53, and taxanes may be effective against gastric cancer cells, which frequently have p53 mutations [33,34] These compounds have high sensitivity against poorly differentiated adenocarcinoma, which is a common type of peritoneal tumor, and some of these compounds, when administered intravenously, are transported into the peritoneal cavity [35,36]. It is hoped that this review will help renew the interest of oncologists in IPC
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