Surgery is the only curative therapeutic approach for gastrointestinal tumors. If the tumor is deeply Infiltrating through serosa or invading regional lymph nodes, the 5-year patient's survival is about 60 % and < 40 %, respectively. The natural history and prognosis of neoplasms from colon, rectum and stomach are different. Despite the unsatisfactory results obtained with radical treatment of advanced disease, there are positive studies on adjuvant treatment of colon and rectal cancer, whereas the role of such an approach is still controversial for gastric cancer. The combination of fluorouracil containing chemotherapy with radiotherapy was suggested as the most effective adjuvant treatment for patients with Dukes’ B and C rectal cancer. However, the choice of chemotherapeutic regimen is still debated. A recent report, from the North Central Cancer Tumor Group, stated survival and disease-free survival advantages for patients with Dukes’ C colon cancer treated with FU + levamisole for 1 year after radical surgery. Since this regimen was not proven effective in advanced disease, ongoing adjuvant trials are comparing it with the combination of FU + biochemical modulator. The role of adjuvant therapy for gastric cancer is debated. The recent development of regimens active on advanced disease result in more promising future adjuvant trials.
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References
1.
AlcobendasF., MillaA., EstapeJ., CurtoJ., PeraC.: Mitomycin C as an adjuvant in resected gastric cancer.Ann. Surg., 178: 13–17, 1983.
2.
AllumW., HallisseyN., KellyK.: Adjuvant chemotherapy in operable gastric cancer: 5-year follow-up of first British stomach cancer group trial.Lancet, 1: 571–574, 1989.
3.
ArnaudJ.P., BuyseM., NordlingerB., MartinF., PectorJ.C., ZeitounP., AdloffA., DuezN.: Adjuvant therapy of poor prognosis colon cancer with levamisole: Results of an EORTC double-blind randomized clinical trial.Br. J. Surg., 76: 284–289, 1989.
4.
BakerL.H., TalleyR.W., MatterR., LehaneD.E., RuffnerB.W., JonesS.E., MorrisonF.S., StephensR.L., GehanE.A., VaitkeviciusV.K.: Phase III comparison of the treatment of advanced gastrointestinal cancer with bolus weekly 5-Fu, versus Methyl-CCNU plus bolus weekly 5-Fu: a Southwest Oncology Group Study.Cancer, 38: 1–7, 1976.
5.
BruknerH.W., MotwaniB.T.: Chemotherapy and advanced cancer of the colon and rectum.Semin. Oncol., 18, 5: 443–461, 1991.
6.
BuyseM., Zeleniuch-JacquotteA., ChalmersT.C.: Adjuvant therapy of colorectal cancer: Why we still don't know.JAMA, 259: 3571–3578, 1988.
7.
CalabrettaB., KaczmarekL., MingP.M., AuF., MingS.C.: Expression of c-myc and other cell cycle-dependent genes in human colon neoplasia.Cancer Res., 45: 6000–6004, 1985.
8.
CohenA.M., ShankB., FriedmanM.A.: Colorectal cancer. In: DevitaV.T., HellmanS., RosenbergS.A. (Eds.): Cancer: Principles and Practice of Oncology, pp. 895–964. Lippincott, Philadelphia, 1989.
9.
CoombesR.C., ScheinP.S., ChilversC.E., WilsJ., BerettaG., BlissJ.M., RuttenA., AmadoriD., Cortes-FunesH., Villar-GrimaltA.: A randomized trial comparing adjuvant fluorouracil, doxorubicin and mitomycin with no treatment in operable gastric cancer.J. Clin. Oncol., 8: 1362, 1990.
10.
DouglassH.O., LavinP.T., GoudsmitA., KlassenD.J.: Phase II-III evaluation of combinations of methyl-CCNU, mitomycin-C, adriamycin and 5-fluorouracil in advanced measurable gastric cancer.Proc. Am. Soc. Clin. Oncol., 2: 121, 1983.
11.
DiwightR.W.: Adjuvant chemotherapy in cancer of the large bowel.Am. J. Surg., 107: 609–613, 1964.
12.
EngstromP., LavinP., DouglasH., BrunnerK.W.: Postoperative adjuvant 5-fluorouracil plus methyl-CCNU therapy for gastric cancer patients.Cancer, 55: 1868–1873, 1985.
13.
EstapeJ., GrauJ.J., LocobendasF., CurtoJ., DanielsM., VignolasN., PeraC.: Mitomycin C as an adjuvant treatment to resected gastric cancer.Ann. Surg., 213: 219–221, 1991.
14.
FisherB., WolmarkN., RocketteH., RedmondC., DeutschM., WickerhamD.L., FisherE.R., CaplanR.: Postoperative adjuvant chemotherapy or radiation therapy for rectal cancer: results from NSABP protocol R-01. J.Natl. Cancer Inst., 80: 21–29, 1988.
15.
Gastrointestinal Tumor Study Group: Controlled trial of adjuvant chemotherapy following curative resection for gastric cancer.Cancer,49: 1116–1122, 1982.
16.
Gastrointestinal Tumor Study Group: Prolongation of disease free interval in surgically treated rectal carcinoma.N. Engl. J. Med., 312: 1465–1472, 1985.
17.
HattoriT., MoriA., HirataK., ItoI.: Five-year survival rate of gastric cancer patients treated with gastrectomy, large-dose mitomycin-C and/or allogenic bone marrow transplantation.Jpn. J. Cancer Res. (Gann.), 63: 517–522, 1972.
18.
HigginsG.A., AmedeoJ.H., McElhinneyJ.: Efficacy of prolonged intermittent therapy with combined 5-FU and methyl-CCNU following resection for carcinoma of the large bowel.Cancer, 53: 1–8, 1984.
19.
HigginsG., AmadeoJ., SmithD.E., HumphreyE.W., KeehnR.J.: Efficacy of prolonged intermittent therapy with combined 5-FU and methyl-CCNU following resection for gastric carcinoma.Cancer, 52: 1105–1112, 1983.
20.
InokuchiK., HattoriT., TaguchiT., AbeO., OgawaN.: Postoperative adjuvant chemotherapy for gastric carcinoma - analysis of data on 1,805 patients followed for 5 years.Cancer, 53: 2293–2397, 1984.
21.
GremJ.L.: Levamisole as a therapeutic agent for colorectal carcinoma.Cancer Cells, 2: 131–137, 1990.
KemenyN.: Role of chemotherapy in the treatment of colorectal carcinoma.Semin. Surg. Oncol., 3: 190–214, 1987.
24.
KennedyB.J.: TNM classification for stomach cancer.Cancer, 26: 971–983, 1979.
25.
KleinH.O.: Long-term results with FAMTX (5-fluorouracil, adriamycin, methotrexate) in advanced gastric cancer.Anticancer Res., 9: 1025–1026, 1989.
26.
KodamaY., SugimaschiK., SoejimaK., MatsusakaT.: Evaluation of extensive lymph node dissection of carcinoma of the stomach.World J. Surg., 5: 241–248, 1981.
LaurieJ.A., MoertelC.G., FlemingT.R., WieandH.S., LeighJ.E., RubinJ., McCormackG.W., GerstnerJ.B., KrookJ.E., MailliardJ.: Surgical adjuvant therapy of large-bowel carcinoma: An evaluation of levamisole and the combination of levamisole and fluorouracil.J. Clin. Oncol., 7: 1447–1456, 1989.
29.
LessnerH.E., MayerR.J., EllenbergS.: Adjuvant therapy of colon cancer - Results of a prospectively randomized trial.N. Eng. J. Med., 310: 737–743, 1984.
30.
MacDonaldJ.S., ScheinP.S., WoolleyP.V.: 5-Fluorouracil, doxorubicin and mitomycin (FAM) combination chemotherapy for advanced gastric cancer.Ann. Intern. Med., 93: 533–536, 1980.
31.
MachoverD., Goldschmidt, CholletP., MetzgerG., ZittounJ., MarquetJ., VandenbulckeJ.M., MissetJ.L., SchwarzenbergL.: Treatment of advanced colorectal and gastric adenocarcinoma with 5-fluorouracil and high-dose folinic-acid.J. Clin. Oncol., 4: 685–696, 1986.
32.
MetzgerU., LafferU., CastiglioneM., SennH.J. for the Swiss Group for Clinical Cancer Research: Adjuvant intraportal chemotherapy for colorectal cancer - 4 year results of the randomized Swiss study (Sakk 40/81). Proc.Am. Soc. Clin. Oncol., 8: 105, 1989.
33.
MoertelC.G., FlemingT.R., MacDonaldJ.S., HallerD., LaurieJ.: Levamisole and fluorouracil for adjuvant therapy for resected colon carcinoma.N. Engl. J. Med., 322: 352–358, 1990.
34.
MoertelC.G., FlemingT.R., MacDonaldJ., HallerD., LaurieJ.: The intergroup study of fluorouracil (5-FU) plus levamisole (Lev) and levamisole alone as adjuvant therapy for stage C colon cancer. A final report abstr. 457. Proc.Am. Soc. Clin. Oncol., 11: 161, 1992.
35.
MoertelC.G., LavinP.T.: An evaluation of 5-FU, nitrosourea, and « lactone » combinations in the therapy of upper gastrointestinal cancer.Proc. Am. Assoc. Cancer Res. and ASCO, 18: 344, 1977.
36.
MoertelC.G., LoprinziL.L., WitzigT.E., WieandH.S., GonchoroffN.J., ReimanH.M., GalandiukS., FitzgibbonsR.J., BarlowJ.F., DonohueJ.H.: The dilemma of B2 colon cancer. Is adjuvant therapy justified? A Mayo/North Central Cancer Therapy Group Study.Proc. Am. Soc. Clin. Oncol., 9: 108, 1990.
37.
MoertelC.G., MittelmanA., BakemeierR.F., EngstromP., HarleyJ.: Sequential and combination chemotherapy of advanced gastric cancer.Cancer, 38: 678–682, 1976.
38.
NakajimaT., TakahashiT., TakagiK., KunoK., KajitaniT.: Comparison of 5-fluorouracil with ftorafur in adjuvant chemotherapies with combined inductive and maintenance therapies for gastric cancer.J. Clin. Oncol., 2: 1366–1371, 1984.
39.
NIH Consensus Conference on Adjuvant Therapy for Patients with Colon and Rectal Cancer.JAMA, 264: 1444–1450, 1990.
40.
NiimotoM., HattoriT., TamadaR., SugimachiK., InorkuchiK., OgawaN.: Postoperative adjuvant immunochemotherapy with mitocymin-C, Farlutal and PSK for gastric cancer, an analysis of data on 579 patients followed for five years.JPN J. Surg., 18: 681–686, 1988.
41.
NoguchiY., ImadaT., MatsumotoA.: Radical surgery for gastric cancer: A review of the Japanese experience.Cancer, 64: 2053–2062, 1989.
42.
OkudaH., SuzukiS., SuzukiH., KurokawaK., KitamuraY., MitsunagaA., HashimotoH., ObataH.: Diagnosis and prognosis of early gastric cancer, the experience in Japan.Trop, Gastroenterol., 9: 7–13, 1988.
43.
PanettiereF.J., GoodmanP.J., CostanziJ.J., CruzA.B.Jr., VaitkeviciusV.K., McCrackenJ.D., BrownleeR.W., LaufmanL., StephenR.L., BonnetJ.: Adjuvant therapy in large bowel adenocarcinoma: Long-term results of a Southwest Oncology Group study.J. Clin. Oncol., 6: 947–954, 1988.
44.
PorshenR., KriegelA., LangenC., ClassenS., HilseM., LoheB., HengelK.J., BochardF.: Assessment of proliferative activity in carcinomas of the human alimentary tract by Ki-67 immunostaining.Int. J. Cancer, 4: 688–691, 1991.
45.
PoseyL.E., MorganL.R.: Methyl-CCNU versus methyl-CCNU and 5-fluorouracil in carcinoma of the large bowel.Cancer Treat. Rep., 61: 1453–1458, 1977.
46.
PreusserP., WilkeH., AchterrathW., FinkU., LenazL., HeinickeA., MeyerJ., MeyerH.J., BuenteH.: Phase II study with the combination etoposide, doxorubicin and cisplatin in advanced measurable gastric cancer.J. Clin. Oncol., 7: 1310–1317, 1989.
47.
RougierP.H., ZarbaJ., DucreuxM.: Efficacy of combined 5-FU and CDDP in advanced pancreatic adenocarcinoma (APC).International Conference on Biology and Treatment of Gastrointestinal Malignancies. Frankfurt, February 1992 (Abstr.).
SilverbergE., BoringC.C., SquiresT.S.: Cancer statistics, 1990.C.A., 40: 9–26, 1990.
50.
TaguchiT., UsuganeS., InokuchiK.: Efficacy of postoperative cancer chemotherapy with MMC and tegafur for stomach cancer, SACGC the 2nd report.(In Japanese) Gan to Kagakuryoho (Cancer Chemotherapy), 12: 1833–1839, 1985.
51.
TaylorI., MachinD., MuleeM., TrotterG., CookeT., WestC.: A randomized controlled trial of adjuvant portal vein cytotoxic perfusion in colorectal cancer.Br. J. Surg., 72: 359–363, 1985.
52.
The Italian Gastrointestinal Tumor Study Group: Adjuvant treatments following curative resection for gastric cancer.Br. J. Surg., 75: 1100–1104, 1988.
53.
VerhaegenH.: Post-operative levamisole in colorectal cancer. In RainerH. (Ed.): Immunotherapy of Malignant Diseases, pp. 94–101. Schattauer-Verlag, Stuttgart, 1978.
Weaver D., Lindblad A.S., for the Gastrointestinal Tumor Study Group (GITSG): Radiation therapy and 5-fluorouracil (5-FU) with or without MeCCNU for the treatment of patients with surgically adjuvant adenocarcinoma of the rectum.Proc. ASCO,9: 106, 1990.
56.
WilkeH., PreusserP., FinkU., AchterrathW., MeyerH.J., StahlM., LenazL., MeyerJ., SiewertJ.R., GeerlingsH.: New developments in the treatment of gastric carcinoma.Semin. Oncol.,17 (Suppl. 2): 61–70, 1990.
57.
WilsJ., CoombesR.C., ChilversC., PalmerA., BlissJ., AmadoriD., BerettaG., Cortes-FunesH., McArdleC., RauscheckerH., Villar-GrimaltA., ScheinP.: Randomized trial of FAM chemotherapy versus control adjuvant treatment for resected gastric cancer: 4-5 year results.Proc. ASCO, 7: 97: 1988.
58.
WilsJ., WagenerD.J. Th.: Combined modality adjuvant treatment of high-risk rectal cancer: a treatment of choice or a choice of treatment? Ann.Oncol., 3: 197–199, 1992.
59.
WindleR., BellP.R.F., ShawD.: Five years results of a randomized trial of adjuvant 5-fluorouracil and levamisole in colorectal cancer.Br. J. Surg., 74: 569–572, 1987.
60.
WolmarkN., FisherB., RocketteH., RedmondC., WickerhamD.L., FisherE.R., JonesJ., GlassA., LernerH., LawrenceW.: Postoperative adjuvant chemotherapy or BCG for colon cancer: Results from NSABP protocol C-01. J.Natl. Cancer Inst., 80: 30–36, 1988.
61.
WolmarkN., RocketteH., WickerhamD.L., FisherB., RedmondC., FisherE.R., PotvinM., DaviesR.J., JonesJ., RobidouxA.: Adjuvant therapy of Dukes’ A, B, and C adenocarcinoma of the colon with portal vein fluorouracil hepatic infusion: Preliminary results of NSABP protocol C-02. J.Clin. Oncol., 8: 1466–1475, 1990.
