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. 1998 Sep;228(3):347–354. doi: 10.1097/00000658-199809000-00007

Prospective randomized trial of early postoperative intraperitoneal chemotherapy as an adjuvant to resectable gastric cancer.

W Yu 1, I Whang 1, I Suh 1, A Averbach 1, D Chang 1, P H Sugarbaker 1
PMCID: PMC1191489  PMID: 9742917

Abstract

OBJECTIVE: Surgeons have postulated on numerous occasions that cancer resection may participate in the dissemination of a malignancy. This randomized trial sought to determine whether a large volume of chemotherapy solution used perioperatively to flood the peritoneal cavity could eliminate microscopic residual disease and thereby improve survival of patients with gastric cancer. SUMMARY BACKGROUND DATA: Surgical treatment failures in patients with gastric cancer are confined to the abdomen in most patients. Resection site and peritoneal surface spread, along with liver metastases, are the most common areas of recurrence. Survival and quality of life of patients with gastric cancer would be improved if disease progression at these anatomic sites was reduced. METHODS: In a prospective randomized trial of 248 patients, intraperitoneal mitomycin C on day 1 and intraperitoneal 5-fluorouracil on days 2 through 5 were administered after gastric cancer resection. Patients who were thought to have stage II or stage III disease were randomized after resection to surgery alone versus surgery plus early postoperative intraperitoneal chemotherapy. After final pathologic examinations, there were 39 patients with stage I, 50 with stage II 95 with stage III, and 64 with resected stage IV cancer. RESULTS: The 5-year survival of the surgery-only group was 29.3%, and the surgery-plus-intraperitoneal chemotherapy group was 38.7% (p = 0.219). In a subset analysis, the patients with stage I, stage II, and stage IV disease showed no statistically significant difference in survival. The 5-year survival rate of patients with stage III disease who underwent surgery only was 18.4% versus a survival rate of 49.1% for patients who underwent surgery plus intraperitoneal chemotherapy (p = 0.011). CONCLUSIONS: In a subset analysis, patients with stage III gastric cancer have shown a statistically significant improvement in survival when treated with perioperative intraperitoneal chemotherapy. Further studies in patients with gastric cancer with surgically directed chemotherapy are suggested.

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Selected References

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  1. Akoh J. A., Macintyre I. M. Improving survival in gastric cancer: review of 5-year survival rates in English language publications from 1970. Br J Surg. 1992 Apr;79(4):293–299. doi: 10.1002/bjs.1800790404. [DOI] [PubMed] [Google Scholar]
  2. Averbach A. M., Sugarbaker P. H. Methodologic considerations in treatment using intraperitoneal chemotherapy. Cancer Treat Res. 1996;82:289–309. doi: 10.1007/978-1-4613-1247-5_18. [DOI] [PubMed] [Google Scholar]
  3. COLE W. H., ROBERTS S. S., WEBB R. S., Jr, STREHL F. W., OATES G. D. DISSEMINATION OF CANCER WITH SPECIAL EMPHASIS ON VASCULAR SPREAD AND IMPLANTATION. Ann Surg. 1965 May;161:753–770. doi: 10.1097/00000658-196505000-00014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cunliffe W. J., Sugarbaker P. H. Gastrointestinal malignancy: rationale for adjuvant therapy using early postoperative intraperitoneal chemotherapy. Br J Surg. 1989 Oct;76(10):1082–1090. doi: 10.1002/bjs.1800761030. [DOI] [PubMed] [Google Scholar]
  5. FISHER E. R., TURNBULL R. B., Jr The cytologic demonstration and significance of tumor cells in the mesenteric venous blood in patients with colorectal carcinoma. Surg Gynecol Obstet. 1955 Jan;100(1):102–108. [PubMed] [Google Scholar]
  6. Fisher B., Gunduz N., Saffer E. A. Influence of the interval between primary tumor removal and chemotherapy on kinetics and growth of metastases. Cancer Res. 1983 Apr;43(4):1488–1492. [PubMed] [Google Scholar]
  7. Fujimura T., Yonemura Y., Muraoka K., Takamura H., Hirono Y., Sahara H., Ninomiya I., Matsumoto H., Tsugawa K., Nishimura G. Continuous hyperthermic peritoneal perfusion for the prevention of peritoneal recurrence of gastric cancer: randomized controlled study. World J Surg. 1994 Jan-Feb;18(1):150–155. doi: 10.1007/BF00348209. [DOI] [PubMed] [Google Scholar]
  8. Gunderson L. L., Sosin H. Adenocarcinoma of the stomach: areas of failure in a re-operation series (second or symptomatic look) clinicopathologic correlation and implications for adjuvant therapy. Int J Radiat Oncol Biol Phys. 1982 Jan;8(1):1–11. doi: 10.1016/0360-3016(82)90377-7. [DOI] [PubMed] [Google Scholar]
  9. Gunduz N., Fisher B., Saffer E. A. Effect of surgical removal on the growth and kinetics of residual tumor. Cancer Res. 1979 Oct;39(10):3861–3865. [PubMed] [Google Scholar]
  10. Hagiwara A., Takahashi T., Kojima O., Sawai K., Yamaguchi T., Yamane T., Taniguchi H., Kitamura K., Noguchi A., Seiki K. Prophylaxis with carbon-adsorbed mitomycin against peritoneal recurrence of gastric cancer. Lancet. 1992 Mar 14;339(8794):629–631. doi: 10.1016/0140-6736(92)90792-2. [DOI] [PubMed] [Google Scholar]
  11. Hallissey M. T., Dunn J. A., Ward L. C., Allum W. H. The second British Stomach Cancer Group trial of adjuvant radiotherapy or chemotherapy in resectable gastric cancer: five-year follow-up. Lancet. 1994 May 28;343(8909):1309–1312. doi: 10.1016/s0140-6736(94)92464-3. [DOI] [PubMed] [Google Scholar]
  12. Hamazoe R., Maeta M., Kaibara N. Intraperitoneal thermochemotherapy for prevention of peritoneal recurrence of gastric cancer. Final results of a randomized controlled study. Cancer. 1994 Apr 15;73(8):2048–2052. doi: 10.1002/1097-0142(19940415)73:8<2048::aid-cncr2820730806>3.0.co;2-q. [DOI] [PubMed] [Google Scholar]
  13. Hermans J., Bonenkamp J. J., Boon M. C., Bunt A. M., Ohyama S., Sasako M., Van de Velde C. J. Adjuvant therapy after curative resection for gastric cancer: meta-analysis of randomized trials. J Clin Oncol. 1993 Aug;11(8):1441–1447. doi: 10.1200/JCO.1993.11.8.1441. [DOI] [PubMed] [Google Scholar]
  14. Iitsuka Y., Kaneshima S., Tanida O., Takeuchi T., Koga S. Intraperitoneal free cancer cells and their viability in gastric cancer. Cancer. 1979 Oct;44(4):1476–1480. doi: 10.1002/1097-0142(197910)44:4<1476::aid-cncr2820440442>3.0.co;2-r. [DOI] [PubMed] [Google Scholar]
  15. Ikeguchi M., Kondou A., Oka A., Tsujitani S., Maeta M., Kaibara N. Effects of continuous hyperthermic peritoneal perfusion on prognosis of gastric cancer with serosal invasion. Eur J Surg. 1995 Aug;161(8):581–586. [PubMed] [Google Scholar]
  16. Jacquet P., Stuart O. A., Dalton R., Chang D., Sugarbaker P. H. Effect of intraperitoneal chemotherapy and fibrinolytic therapy on tumor implantation in wound sites. J Surg Oncol. 1996 Jun;62(2):128–134. doi: 10.1002/(SICI)1096-9098(199606)62:2<128::AID-JSO9>3.0.CO;2-A. [DOI] [PubMed] [Google Scholar]
  17. Kaibara N., Sumi K., Yonekawa M., Ohta M., Makino M., Kimura O., Nishidoi H., Koga S. Does extensive dissection of lymph nodes improve the results of surgical treatment of gastric cancer? Am J Surg. 1990 Feb;159(2):218–221. doi: 10.1016/s0002-9610(05)80265-x. [DOI] [PubMed] [Google Scholar]
  18. Koga S., Hamazoe R., Maeta M., Shimizu N., Murakami A., Wakatsuki T. Prophylactic therapy for peritoneal recurrence of gastric cancer by continuous hyperthermic peritoneal perfusion with mitomycin C. Cancer. 1988 Jan 15;61(2):232–237. doi: 10.1002/1097-0142(19880115)61:2<232::aid-cncr2820610205>3.0.co;2-u. [DOI] [PubMed] [Google Scholar]
  19. Korenaga D., Moriguchi S., Orita H., Kakeji Y., Haraguchi M., Maehara Y., Sugimachi K. Trends in survival rates in Japanese patients with advanced carcinoma of the stomach. Surg Gynecol Obstet. 1992 May;174(5):387–393. [PubMed] [Google Scholar]
  20. Landry J., Tepper J. E., Wood W. C., Moulton E. O., Koerner F., Sullinger J. Patterns of failure following curative resection of gastric carcinoma. Int J Radiat Oncol Biol Phys. 1990 Dec;19(6):1357–1362. doi: 10.1016/0360-3016(90)90344-j. [DOI] [PubMed] [Google Scholar]
  21. Lise M., Nitti D., Marchet A., Sahmoud T., Buyse M., Duez N., Fiorentino M., Dos Santos J. G., Labianca R., Rougier P. Final results of a phase III clinical trial of adjuvant chemotherapy with the modified fluorouracil, doxorubicin, and mitomycin regimen in resectable gastric cancer. J Clin Oncol. 1995 Nov;13(11):2757–2763. doi: 10.1200/JCO.1995.13.11.2757. [DOI] [PubMed] [Google Scholar]
  22. MELENEY F. L., JOHNSON B. A., TENG P. Further experiences with local and systemic bacitracin in the treatment of various surgical and neurosurgical infections and certain related medical infections. Surg Gynecol Obstet. 1952 Apr;94(4):401–425. [PubMed] [Google Scholar]
  23. Maruyama K., Okabayashi K., Kinoshita T. Progress in gastric cancer surgery in Japan and its limits of radicality. World J Surg. 1987 Aug;11(4):418–425. doi: 10.1007/BF01655804. [DOI] [PubMed] [Google Scholar]
  24. Sautner T., Hofbauer F., Depisch D., Schiessel R., Jakesz R. Adjuvant intraperitoneal cisplatin chemotherapy does not improve long-term survival after surgery for advanced gastric cancer. J Clin Oncol. 1994 May;12(5):970–974. doi: 10.1200/JCO.1994.12.5.970. [DOI] [PubMed] [Google Scholar]
  25. Shchepotin I. B., Chernyi V. A. Effektivnost' vnutribriushinnoi khimioterapii v kombinirovannom lechenii raka zheludka. Klin Khir. 1990;(5):7–9. [PubMed] [Google Scholar]
  26. Stearns M. W., Jr, Schottenfeld D. Techniques for the surgical management of colon cancer. Cancer. 1971 Jul;28(1):165–169. doi: 10.1002/1097-0142(197107)28:1<165::aid-cncr2820280133>3.0.co;2-8. [DOI] [PubMed] [Google Scholar]
  27. Sugarbaker P. H., Graves T., DeBruijn E. A., Cunliffe W. J., Mullins R. E., Hull W. E., Oliff L., Schlag P. Early postoperative intraperitoneal chemotherapy as an adjuvant therapy to surgery for peritoneal carcinomatosis from gastrointestinal cancer: pharmacological studies. Cancer Res. 1990 Sep 15;50(18):5790–5794. [PubMed] [Google Scholar]
  28. Sugarbaker P. H. Peritoneal carcinomatosis: natural history and rational therapeutic interventions using intraperitoneal chemotherapy. Cancer Treat Res. 1996;81:149–168. doi: 10.1007/978-1-4613-1245-1_13. [DOI] [PubMed] [Google Scholar]
  29. Tanida O., Kaneshima S., Iitsuka Y., Kuda H., Kiyasu Y., Koga S. Viability of intraperitoneal free cancer cells in patients with gastric cancer. Acta Cytol. 1982 Sep-Oct;26(5):681–687. [PubMed] [Google Scholar]
  30. Turnbull R. B., Jr, Kyle K., Watson F. R., Spratt J. Cancer of the colon: the influence of the no-touch isolation technic on survival rates. Ann Surg. 1967 Sep;166(3):420–427. doi: 10.1097/00000658-196709000-00010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Wanebo H. J., Kennedy B. J., Chmiel J., Steele G., Jr, Winchester D., Osteen R. Cancer of the stomach. A patient care study by the American College of Surgeons. Ann Surg. 1993 Nov;218(5):583–592. doi: 10.1097/00000658-199321850-00002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Wils J., Meyer H. J., Wilke H. Current status and future directions in the treatment of localized gastric cancer. Ann Oncol. 1994;5 (Suppl 3):69–72. doi: 10.1093/annonc/5.suppl_3.s69. [DOI] [PubMed] [Google Scholar]
  33. Wisbeck W. M., Becher E. M., Russell A. H. Adenocarcinoma of the stomach: autopsy observations with therapeutic implications for the radiation oncologist. Radiother Oncol. 1986 Sep;7(1):13–18. doi: 10.1016/s0167-8140(86)80120-7. [DOI] [PubMed] [Google Scholar]
  34. Yu W. S., Sugarbaker P. H. Early postoperative intraperitoneal chemotherapy for gastric cancer. Cancer Treat Res. 1991;55:265–275. doi: 10.1007/978-1-4615-3882-0_14. [DOI] [PubMed] [Google Scholar]

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