Phase III Study of the Effect of Radical Gastric Surgery Versus Conventional Surgery on Recurrence and Survival in Patients With Advanced Stage Gastric Cancer.
* TREATMENT PLAN
Patients are randomized intraoperatively into arm I (conventional [R0/R1] gastrectomy) or
arm II (extended radical [R3] lymph node dissection).
Arm I: Resection of stomach, greater omentum, lesser omentum, and adjacent organ(s) when the
primary tumor invaded directly. A total or distal subtotal gastrectomy is decided by the
proximal distance from cardia to the tumor. A margin of 3 cm was required for well-defined
(Borrmann I or II) tumors, and of 5 cm for ill-defined (Borrmann III or IV) tumors. When a
total gastrectomy is performed, the distal pancreas and spleen should be preserved unless
there is direct invasion into these organs. The left gastric artery should not be ligated at
its origin but distal to its bifurcation into ascending and descending branches.
Arm II: The procedure are the same as in Arm I, additionally, extended lymph node dissection
includes dissection of the N1, N2 and N3 nodes. These groups (N) are comprised of lymph node
stations which depended on the location of the primary tumors (Fig. 1).
1. For N2 dissection, the left gastric artery is ligated at its origin to facilitate the
dissection of No.7. If a total gastrectomy is indicated, a splenectomy is essential for
the dissection of station No. 10, and a distal pancreatectomy for the dissection of
station No.11. Combined resection of these adjacent organs is not performed during a
distal subtotal gastrectomy.
2. If the primary cancer is located at the middle or lower third of stomach, No.1 (nodes
at right cardiac) and 11 (nodes along the splenic artery) are excised routinely for
frozen section before gastric resection. If no cancer metastasis is seen in both No.1
and 11 lymph nodes is performed. If only No. 1 lymph nodes is positive for cancer
metastasis, total gastrectomy is performed instead of distal subtotal resection. If No.
11 lymph nodes are positive, splenectomy and distal pancreatectomy are performed in
addition to the radical resection of the stomach and lymph nodes.
3. For N3 dissection: No. 12 (nodes in the hepatoduodenal ligament), No. 13 (nodes at
retropancreatic region) and No. 14 (nodes at the root of mesentery) are dissected.
For patients who had gastric cancer recurrence after gastrectomy, chemotherapy with
cisplatin、 5-FU、Leucovorin will be given.
Cisplatin 20mg/m2 5-FU 450 mg/m2 Leucovorin 90 mg/m2
The above three drugs to be given in 500ml of normal saline and infused intravenously
simultaneously over 96 hours and repeated every 3 weeks. (21days)
Dose modification： Delay treatment for one week (if WBC<4000/dl immediately before
treatment). Reduce dose of subsequent cycles of 5-FU by 20% if WBC nadir <1000/dl.
Delay treatment for one week (if there is oral mucositis or diarrhea immediately before
treatment). Reduce dose of subsequent cycles of 5-FU by 10% for grade 2 and 20% for grade 3
or 4 mucositis or diarrhea.
Stop treatment for any grade 4 non-hematological toxicity. Stop cisplatin treatment if serum
creatinine > 2mg/dl.
Duration of treatment： Continue treatment for patients until disease progression.
* DATA AND PROTOCOL MANAGEMENT 10.1 Registration, randomization will be performed by the
Cancer Clinical Trial Operations Office by calling 789-9046. (47)& 7852459.
Quality control of the data will be performed by the Cancer Clinical Trial Operations
Office, Institute of Biomedical Sciences, Academia Sinica.
Data will be evaluated by the statistician and the study chairman before data analyzed
10.2 Protocol Compliance: the attending physician and oncology research nurse must see each
patient prior to treatment and at follow up to ensure all investigations, treatment
procedures and data records are done and recorded according to protocol.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
We expect to enter 50 patients per year and finish accrual of patient within 2.5 years.
Chew-Wun Wu, Ph.D.
Taipei Veterans General Hospital,Taiwan
Taiwan: Department of Health