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Adjuvant therapy in gastric cancer.

Romeo Giuli MD, resident.
School of General and Emergency Surgery.
University of Siena.   Italy.

September 2001.     Review Article.    To the first updating    To the second updating

Postoperative chemotherapy as an adjuvant to potentially curative resection of gastric cancer remains investigational despite more than 30 years of investigation in the West.
On the basis of the results from the numerous trials of various adjuvant therapies for patients with gastric carcinoma, the routine use of these therapies cannot be recommended currently ( 1, 5 ).

In Asia the perception of the benefit of adjuvant therapy differs from that in the West. However many of these results have been found only in subgroup analyses, which detracts from their validity. The studies demonstrating a benefit of immunochemotherapy often have lacked treatments controls.
The benefit seen in the Asia studies may be due to early initiation of chemotherapy and the use of immunotherapy, which in general has received more emphasis in Asia.
In fact adjuvant therapy in patients in the west is often initiated 6 weeks after surgery, and this gives the microscopic tumor burden time to increase.Such delayed therapy is likely to be ineffective.

Many newer approaches warrant investigation: more effective chemotherapy combinations or chemoradiotherapy; drugs with newer mechanisms of actions, such as antiangiogenesis inhibitors, metalloproteinase inhibitors, antibodies to oncogenes, or gene therapy; and preoperative therapy of potentially resectable gastric carcinoma ( 1 ).

MacDonald and colleagues demonstrate (in a randomized study) that chemoradiotherapy after resection for gastric cancer (fluorouracil plus leucovorin and radiation) significantly improves relapse-free and overall survival among patients at high risk for recurrence of adenocarcinoma of the stomach or gastroesophageal junction who have undergone curative resection.
Resection of all detectable disease was required for partecipation in the trial. An extensive (D2) lymph node dissection was recommended but patients were not excluded on the basis of the extent of lymphadenectomy ( 2, 3, 4 ).

Moreover we cite two recent korean studies published in Cancer 2001 about adjuvant chemotherapy.

In the first Jeen and colleagues note that the results of chemotherapy for patients with gastric carcinoma generally have been modest, although regimens developed more recently have produced higher response rates. One such regimen is epirubicin, cisplatin and protracted infusion of 5-fluorouracil (ECF). The advantage of a long-term oral administration of uracil and tegafur (UFT) is that this treatment may be used to mimic the protracted infusion of 5 fluorouracil (5FU). In addition UFT treatment combined with leucovorin had a favourable activity and tolerable toxicity in patients with advanced gastric carcinoma. Instead of the inconvenience of an infusion pump and intravenous catheter for the protracted infusion of 5FU, the authors administered UFT plus leucovorin in an ECF regimen for the treatment of patients with advanced gastric carcinoma ( 6 ).

In the second study Jeung and colleagues underline that adjuvant chemotherapy with 5-FU plus doxorubicin for 60 weeks after D2-3 dissection induced promising survival duration with acceptable toxicities. Full administration of the planned dosage of the combined drugs is recommendable as opposed to early termination of the chemotherapy in gastric carcinoma. Prospective randomized studies based on SDI could induce more information about appropriate dosage and chemotherapy duration of combined regimen for gastric carcinoma ( 7 ).


1) Ken Shimada, Jaffer A Ajani. Adjuvant therapy for gastric canrcinoma patients in the past 15 years. A Review of western and oriental trials. Cancer 1999; 86: 1657-68.

2) J S MacDonald, SR Smalley, J Benedetti et al. Chemoradiotherapy after surgery compared with surgery alone for Adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med, 2001,volume 345: 725-730.

3) MacDonald JS, Smalley s, Benedetti J et al. Postoperative combined radiation and chemotherapy improves disease-free survival (DFS) and overall survival (OS) in resected adenocarcinoma of the stomach and GE junction. Proc Am Soc Clin Oncol 2000; 19: 1a.

4) S Smalley, BenedettiJ et al. Intergroup 0116 ( SWOG 9008)- phase III trial of postoperative adjuvant radiochemotherapy for high risk gastric and gastroesophageal junction Adenocarcinoma: evaluation of efficacy and radiotherapy treatment planning. Int J Radiat Oncol Biol Phys 2000; 48 Suppl: 111-112.

5) CP Scuhmacher, U Fink, K Becker, R Busch, H-J Dittler, James Mueller and J R Siewert. Neoadjuvant therapy for patients with locally advanced gastric carcinoma with etoposide, doxorubicin and cisplatin. Cancer 2001; 91:918-27.

6) Y T Jeen et al. Phase II trial of epirubicin, cisplatin, oral uracil and tegafur and leucovorin in patients with advanced gastric carcinoma. Cancer 2001; 91: 2288-93.

7) HC Jeung et al.Adjuvant 5 fluorouracil plus doxorubicin in D2-3 resected gastric carcinoma. Cancer 2001; 91: 2016-25.

8) YH Kim et al. Paclitaxel, 5 FU and cisplatin combination chemotherapy for the treatment of advanced gastric carcinoma. Cancer 1999; 85: 295-301.

9) Susan Partyka, Pamela Dumas, Jaffer Ajani. Combination chemotherapy with granulocyte-macrophage-colony stimulating factor in patients with locoregional and metatsatic gastric adenocarcinoma. Cancer 1999; 85: 2336-9.

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