TITLE:
Intraperitoneal Chemotherapy as a Multimodal Treatment for Gastric Cancer Patients with Peritoneal Metastasis
AUTHORS:
Sachio Fushida, Katsunobu Oyama, Jun Kinoshita, Tomoya Tsukada, Kouichi Okamoto, Hidehiro Tajima, Itasu Ninomiya, Hirohisa Kitagawa, Takashi Fujimura, Tetsuo Ohta
KEYWORDS:
Peritoneal Metastasis; Gastric Cancer; Intraperitoneal Chemotherapy
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.4 No.9A,
October
10,
2013
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.