Efficacy of HIPEC in the Treatment of Locally Advanced Gastric Cancer After radIcal Gastrectomy With D2
Efficacy of HIPEC in the Treatment of Locally Advanced Gastric Cancer After radIcal Gastrectomy With D2
HIPEC-01 is a prospective, open, randomized multicenter phase III clinical study conducted in
 China. To determine the efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) in the
 treatment of locally advanced gastric cancer, patients are randomized into HIPEC group and
 control group. In HIPEC group, the patients undergo radical gastrectomy with D2
 lymphadenectomy and HIPEC with paclitaxel and postoperative chemotherapy. Patients in the
 control group just undergo radical gastrectomy with D2 lymphadenectomy followed by
 postoperative chemotherapy. Patients in both groups receive 6-8 cycles of postoperative
 systemic chemotherapy (XELOX or SOX regimens) and are followed up for 5 years or until death.
Gastric cancer (GC) is the fourth most common cancer, and the second leading cause of
 cancer-related death worldwide. Advances in diagnostic and therapeutic approaches have
 achieved long-term survival for early GC. However, receiving perioperative/postoperative
 systemic chemotherapy and gastrectomy with D1-D2 lymph node dissection, 5-year survival rates
 of advanced gastric cancer remain under 30%. 40-60% of recurrences are peritoneal and/or
 locoregional. hyperthermic intraperitoneal chemotherapy (HIPEC) technique is increasingly
 used in the curative treatment of primary and digestive peritoneal carcinomatosis, in
 association with cytoreductive surgery. Theoretically, HIPEC eliminates free cancer cells
 that can be released into peritoneal cavity during the gastrectomy and prevents peritoneal
 carcinomatosis recurrences. The benefit of using HIPEC as an adjuvant treatment for advanced
 gastric cancer has been reported in several randomized studies and a meta-analysis. Surgical
 resection combined with HIPEC significantly reduces the peritoneal recurrences and improves
 the overall survival of GC patients. But there is not a prospective and randomized phase III
 clinical study of HIPEC in the treatment of locally advanced gastric cancer after radical
 surgery in China so far.

 In order to evaluate the survival benefit and safety of radical surgery and HIPEC followed by
 postoperative chemotherapy in local advanced gastric cancer, patients who fulfill the
 inclusion and exclusion criteria will be recruited in this study and randomized to two
 treatment groups (HIPEC group and control group). In HIPEC group, the patients undergo
 radical gastrectomy with D2 lymphadenectomy and HIPEC with paclitaxel and postoperative
 chemotherapy. Patients in the control group just undergo radical gastrectomy with D2
 lymphadenectomy followed by postoperative chemotherapy. Patients in both groups receive 6-8
 cycles of postoperative systemic chemotherapy (XELOX or SOX regimens) . Patients are followed
 up for 5 years and the survival outcome will be analyzed.
Inclusion Criteria:

 -  18 < age ≤ 70 years old

 -  Male or Non pregnant female

 -  The Eastern Cooperative Oncology Group (ECOG) status 0-1

 -  T3 or T4 gastric adenocarcinoma (visual determination according to AJCC 2010 7th
 edition)

 -  No distance metastasis, eligible for D2 lymphadenectomy

 -  Have not received cytotoxic chemotherapy, radiotherapy or immunotherapy

 -  White blood cells > 4,000/mm3

 -  neutrophils ≥ 1,500/mm3

 -  platelets ≥ 100,000/mm3

 -  hemoglobin>9g/l

 -  Alanine transaminase (ALT) and aspartate aminotransferase (AST) < or = 2.5 times upper
 limit of nominal (ULN)

 -  total bilirubin (TBIL) < 1.5 times ULN

 -  serum creatinine < 1 times ULN

 -  Having given written informed consent prior to any procedure related to the study

 Exclusion Criteria:

 -  Have other cancer within 5 years

 -  Existence of distance metastasis during surgey (M1)

 -  Prior malignant tumors with detectable signs of recurrence or distant metastasis

 -  Poorly controlled disease e.g. atrial fibrillation, stenocardia, cardiac
 insufficiency, persistent hypertension despite medicinal treatment, ejection
 fraction<50%

 -  Epileptic seizures patients need medicine control

 -  Uncontroled mental disease or mental disorder

 -  Drug abuse or psychological or social factors affect the judgment of results

 -  Contraindication to any therapy contained in this regimen specific to the study

 -  Receiving other chemotherapy, radiotherapy or immunotherapy

 -  Without given written informed consent