Combination Chemotherapy in Treating Patients With Locally Advanced or Metastatic Cancer of the Esophagus

OBJECTIVES:

• Determine the objective tumor response rate in patients with previously untreated locally advanced unresectable or metastatic esophageal cancer treated with irinotecan and cisplatin.
• Determine the dysphagia relief in patients treated with this regimen.
• Determine the time to progression and overall survival of patients treated with this regimen.
• Determine the safety of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive cisplatin IV over 1-2 hours and irinotecan IV over 30 minutes on days 1 and 8. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study within 1 year.

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous cell carcinoma or adenocarcinoma of the esophagus

• Previously untreated
• Locally advanced unresectable or metastatic disease
• More than 50% of tumor must involve esophagus or gastroesophageal (GE) junction if tumor extends below the GE junction into the proximal stomach
• At least 1 unidimensionally measurable lesion

• At least 20 mm by conventional techniques OR
• At least 10 mm by spiral CT scan
• The following are not considered measurable disease:

• Bone lesions
• Leptomeningeal disease
• Ascites
• Pleural/pericardial effusions
• Lymphangitis cutis/pulmonis
• Abdominal masses not confirmed and followed by imaging techniques
• Cystic lesions
• Tumor lesions in previously irradiated areas
• No carcinomatous meningitis or untreated brain metastases

• Brain metastases allowed if asymptomatic and patient is on stable or tapering dose of steroids
• Large pleural effusions must have been previously drained and sclerosed or otherwise controlled

• Small, stable, asymptomatic pleural effusions allowed
• Dysphagia allowed

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy:

• At least 3 months

Hematopoietic:

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

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• AST no greater than 3 times upper limit of normal (ULN) (5 times ULN if liver metastases present)
• No known Gilbert's disease

Renal:

• Creatinine no greater than 1.5 mg/dL
• Calcium less than 12.0 mg/dL

Cardiovascular:

• No history of significant cardiovascular disease
• No inadequately controlled hypertension
• No unstable angina
• No myocardial infarction within the past 6 months
• No ventricular cardiac arrhythmias requiring medication
• No history or treatment for congestive heart failure

Pulmonary:

• No interstitial pneumonia
• No fibroid lung

Other:

• No serious active infection
• No uncontrolled diabetes mellitus (random blood sugar at least 300 mg)
• No peripheral neuropathy grade 2 or greater
• No other malignancy within the past 3 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or any other malignancy that does not carry a worse prognosis than advanced esophageal cancer
• No other serious underlying medical condition that would preclude study
• No other concurrent disease that would preclude study
• No psychiatric illness or other significant mental impairment that would preclude study
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• See Disease Characteristics

Radiotherapy:

• See Disease Characteristics
• At least 2 weeks since prior radiotherapy and recovered
• No prior radiotherapy to the pelvis

Surgery:

• See Disease Characteristics
• Not specified

Other:

• No concurrent phenytoin or phenobarbital