NEW NEOADJUVANT TREATMENT STRATEGIES FOR GASTRIC AND GASTROESOPHAGEAL JUNCTION CANCERS

Objective: The feasibility of neoadjuvantchemotherapy for clinically unresectable gastric and gastroesophageal (GE) junction cancers.Methods: Eleven patients with gastric and GE junction cancers underwent preoperative combined modality chemo and radiotherapy and a subsequent attempt for surgical resection.Results: Combined modality periadjuvant therapies downsized 9 of 11 T3-4 gastric and gastroesophageal junction cancers and produced 4 pathologically proven complete remissions. Treatment appeared to convert lymph nodes to a cancer free status for 7 of 11 patients. After treatment, exploratory surgery found that 3 patients had only minute foci of occult metastatic disease. The quality of the responses was underestimated by both endoscopic ultrasound and CT scans. Responses were sometimes only achieved after 2-3 months of therapy.Conclusion: Combined modality therapydemonstrates the feasibility of a flexible multistep approach to neoadjuvant therapy incorporating new drugs such as methotrexate and hydroxyurea in addition to fluorouracil and cisplatin. Long delays in surgery (gastrectomy) appear to be safe in the context of combined modality therapy. Median survival exceeds 2 years. The experience suggests new early end points for evaluation of neoadjuvant treatments: quality of life, quality of lymph node sterilization and extent of required gastrectomy in comparison to standard surgery.Key Words: Neoadjuvant, Gastric cancer, Gastroesophageal cancer, Combined modality treatment

___

  • Kelsen DP. Adjuvant and neoadjuvant therapy of gastric cancer. Semin-Oncol 1996; 23: 379-389.
  • Gunderson I.L, Sosin ft. Adenocarcinoma of the
  • stomach: Areas of failure in a reoperation
  • seriesisecond or symptomatic look) clinicopathologic correlation and implications for adjuvant therapy. Int J Radiation Oncol Biol Phys 1981; 8:1-1 I.
  • Ajani JA, Ota DPI, Jessup JP1, et al. Resectable gastric carcinoma. An evaluation of preoperative and postoperative chemotherapy. Cancer 1991; 68:1501-1506.
  • Hermans J, Bonenkamp JJ, Boon PIC, et ah. Adjuvant therapy after curative resection for gastric cancer: Meta analysis of randomized trials. J Clin Oncol 1993; I 1:1441 -1447.
  • Regine WF, Mohiuddln M. Impact of adjuvant therapy on locally advanced adenocarcinoma of the stomach. Int J Radiat Oncol Biol Phys 1992; 24:921-927.
  • Kiyabu PI, Leichman L, Chandrasoma P. Effects of preoperative chemotherapy on gastric adenocarcinoma. Cancer 1992; 70:2239-2245.
  • Ajani JA, Player RJ, Ota DPI, et al. Preoperative and postoperative combination chemotherapy for potentially resectable gastric carcinoma. J Hat Cancer Inst 1993; 85:1839-1844.
  • Wilke H, Preusser P, Fink U, et al. Preoperative chemotherapy in locally advanced and non- resectable gastric cancer: A phase II study with etoposide, doxorubicin, cisplatin. J Clin Oncol 1989; 7:1318-1326.
  • Ajani JA, Roth JA, Ryan P1B, et al. Intensive preoperative chemotherapy with colony stimulating factor for resectable adenocarcinoma of the esophagus or gastroesophageal junction. J Clin Oncol 1993; 11:22-28.
  • Rougier P, Plahjoubi PI, Lasser P, et al. Heoadjuvant chemotherapy in locally advanced gastric
  • Marmara Medical Journal Volume 12 No: 1 January 1999
  • carcinoma- a phase II trial with combined continuous intravenous 5fiuorouracii and bolus cisplatinum. Eur J of Cancer ¡994; 30:1269-1275.
  • Tsukiyama 1, Akine Y, Kajiura Y, et al. Radiation therapy for advanced gastric cancer. Int J Radi at Oncol Biol Phys 1988; 15:123-127.
  • Gunderson LL, Burch FA, Donahue Jtl. The role of irradiation as a component of combined modality treatment for gastric cancer. J Infus Chemother 1995; 5:1 17-124.
  • Elinsky BD. The role of radiation therapy in gastric cancer. Semin Oncol 1996; 23:390-396.
  • Bruckner fl. Effective treatment for adenocarcinoma of the stomach when surgery is contraindicated. Am J Gastroenterol 1988; 83:699- 700.
  • Smith JW, Brennan MF, Botet JF, et al. Preoperative endoscopic ultrasound can predict the risk of
  • recurrence after operation for gastric carcinoma. J Clin Oncol 1993; 1 1:2380-2385.
  • Lemoine NR, Jain S, Silvestre F, et al. Amplifications and over expression of the EGF receptor on C-erb B- 2 proto-oncogenes in human stomach cancer. Br J Cancer 1991; 64:79-83.
  • Johnston PG, Lenz fIJ, Leichman CO, et al. Thymidilate synthase protein and gene expression correlate and are associated with response to 5- fluorouracil in human colorectal and gastric tumors. Cancer Res 1995; 55:1407-14 12.
  • Robey-Cafferty SS, Ajani J A, OtaDM, et al. Histologic observations and P-glycoprotein expression in gastric and esophageal adenocarcinomas treated with preoperative chemotherapy. Arch Pathol Lab Med 1991; 115:807-812.