• Analysis of biopsy specimens [ Designated as safety issue: No ]
  
• Drug effect as measured by changes in microarray expression patterns [ Designated as safety issue: No ]
  

• Patterns of gene expression pre- and post-treatment [ Designated as safety issue: No ]
  

OBJECTIVES:

• Determine the maximum tolerated dose of oblimersen administered with cisplatin and fluorouracil in patients with advanced esophageal, gastroesophageal junction, or gastric cancer.
• Determine the toxic effects of this regimen in these patients.

OUTLINE: This is a pilot, multicenter, dose-escalation study of oblimersen.

• Phase I: Patients receive oblimersen IV continuously on days 1-7, fluorouracil IV continuously on days 4-8, and cisplatin IV on day 4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of oblimersen until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional 12 patients are treated at the MTD.

• Phase II: Patients receive treatment as in phase I with oblimersen at the MTD.

PROJECTED ACCRUAL: Approximately 37-97 patients (3-36 for phase I and 34-67 for phase II) will be accrued for this study within 15-18 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the esophagus, gastroesophageal junction, or stomach

  • Squamous cell carcinoma of the esophagus also eligible
• Locally advanced, recurrent, or metastatic disease not amenable to complete surgical resection or definitive radiotherapy
• Clinically evaluable disease

• Measurable disease or clinically evaluable disease

  • Patients with inaccessible tumor tissue must have at least 1 measurable tumor deposit
• No known brain metastases

PATIENT CHARACTERISTICS:

Age

• Over 18

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• More than 12 weeks

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin normal
• AST and ALT no greater than 2.5 times upper limit of normal

Renal

• Creatinine normal OR
• Creatinine clearance at least 60 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception
• No prior allergic reaction attributed to compounds of similar chemical or biological composition to antisense oligonucleotides, cisplatin, fluorouracil, or other study agents
• No other concurrent uncontrolled illness
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• Willing to undergo 2 biopsies (for patients with accessible tumor only, defined as tumors reachable by esophagogastroduodenoscopy OR metastases which can be biopsied with commonly utilized methods [e.g., CT-guided biopsy])

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent growth factors during the first course of study therapy

Chemotherapy

• No more than 1 prior chemotherapy regimen for advanced, recurrent, or metastatic disease

  • Prior significant full-dose chemotherapy (at least 2 months of therapy) during primary treatment is considered a prior regimen of chemotherapy (unless at least 6 months have elapsed since completion of treatment)
  • An additional chemotherapy regimen allowed for recurrent or progressive disease more than 6 months after the completion of prior significant chemotherapy
• At least 3 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• At least 3 weeks since prior radiotherapy and recovered

Surgery

• Prior surgery allowed

Other

• More than 4 weeks since prior photodynamic therapy
• No prior oblimersen
• No other concurrent investigational agents
• No concurrent combination antiretroviral therapy for HIV-positive patients
• Concurrent photodynamic therapy for obstruction untreatable by stent, laser, or dilation allowed