Gastric cancer remains a major health care problem in the United States. While the number of newly diagnosed patients has remained essentially constant over the past 10-15 years, the incidence of proximal gastric cancers (which are more virulent) is rising rapidly. On a global basis, cancer of the stomach is one of the most prevalent malignancies known to man. While surgery remains the mainstay of potentially curative therapy, preoperative staging techniques are unsatisfactory, complete resection is possible in only a minority of patients, and survival rates even for these are poor. A substantial fraction of patients present with advanced inoperable cancer. There is a paucity of data regarding the biology of this important disease. We plan (1) To test the hypothesis that the outcome of high risk patients with local regional gastric cancer can be improved by intensive pre and postoperative adjuvant chemotherapy, given systemically and intraperitoneally (IP). High risk patients will be identified preoperatively using endoscopic ultrasonography and flow cytometry in addition to conventional staging techniques. The preoperative chemotherapy regimen used will be the FAMTX (fluorouracil, methotrexate, adriamycin, leucovorin) regimen, which has been shown in a random assignment MSKCC study to be well tolerated and capable of inducing complete remissions. The IP regimen of cisplatin and FU has already been studied at MSKCC in the postoperative adjuvant setting. (2) The biology of gastric cancer will be intensely studied in the same patient population entering the clinical trials, Using information obtained from earlier studies showing nonrandom chromosomal abnormalities as a guide, we will focus molecular genetic studies on abnormal genes on t;he appropriate chromosomes, and correlate genetic perturbations with clinical outcome. Biological data will be entered into an existing prospective computer data base containing clinical information on surgical and chemotherapy protocols involving the same patients. Sophisticated biostatistical techniques will be used to analyze the potential correlations between clinical and laboratory data.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
7R01CA056125-02
Application #
3200631
Study Section
Special Emphasis Panel (SRC (42))
Project Start
1991-09-30
Project End
1994-08-31
Budget Start
1992-09-01
Budget End
1993-08-31
Support Year
2
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065
Lydiatt, W M; Davidson, B J; Schantz, S P et al. (1998) 9p21 deletion correlates with recurrence in head and neck cancer. Head Neck 20:113-8
Kelsen, D; Karpeh, M; Schwartz, G et al. (1996) Neoadjuvant therapy of high-risk gastric cancer: a phase II trial of preoperative FAMTX and postoperative intraperitoneal fluorouracil-cisplatin plus intravenous fluorouracil. J Clin Oncol 14:1818-28
Davidson, B J; Lydiatt, W M; Abate, M P et al. (1996) Cyclin D1 abnormalities and tobacco exposure in head and neck squamous cell carcinoma. Head Neck 18:512-21
Lydiatt, W M; Murty, V V; Davidson, B J et al. (1995) Homozygous deletions and loss of expression of the CDKN2 gene occur frequently in head and neck squamous cell carcinoma cell lines but infrequently in primary tumors. Genes Chromosomes Cancer 13:94-8
Murty, V V; Li, R G; Mathew, S et al. (1994) Replication error-type genetic instability at 1q42-43 in human male germ cell tumors. Cancer Res 54:3983-5
Mathew, S; Murty, V V; Bosl, G J et al. (1994) Loss of heterozygosity identifies multiple sites of allelic deletions on chromosome 1 in human male germ cell tumors. Cancer Res 54:6265-9
Mitra, A B; Murty, V V; Pratap, M et al. (1994) ERBB2 (HER2/neu) oncogene is frequently amplified in squamous cell carcinoma of the uterine cervix. Cancer Res 54:637-9
Christman, K; Saltz, L; Schwartz, G et al. (1993) Granulocyte colony-stimulating factor: effective in ameliorating fluorouracil-based myelosuppression? J Natl Cancer Inst 85:826-7
Rao, P H; Mathew, S; Lauwers, G et al. (1993) Interphase cytogenetics of gastric and esophageal adenocarcinomas. Diagn Mol Pathol 2:264-8