Bryostatin 1 Plus Paclitaxel in Treating Patients With Locally Advanced or Metastatic Esophageal Cancer or Stomach Cancer

OBJECTIVES:

• Determine the complete and partial response rates in patients with unresectable or metastatic esophageal cancer or carcinoma of the gastroesophageal junction treated with sequential paclitaxel and bryostatin 1.
• Determine the toxicity of this regimen in this patient population.
• Determine the survival of patients after treatment with this regimen.
• Determine the quality of life of patients treated with this regimen.
• Examine pre- and post-treatment tissue biopsies for markers of apoptosis in selected patients.

OUTLINE: This is a multicenter study.

Patients receive paclitaxel IV over 1 hour on day 1 and bryostatin 1 IV over 24 hours on day 2 weekly for 2 weeks. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.

Quality of life is assessed at baseline, after courses 1 and 2, and then after every 2 courses thereafter.

PROJECTED ACCRUAL: A total of 19-33 patients will be accrued for this study within 1-2 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous cell carcinoma or adenocarcinoma of the esophagus or carcinoma of the gastroesophageal (GE) junction

• If tumor extends below GE junction into the proximal stomach, 50% of the tumor must involve the esophagus or GE junction
• No gastric cancer with only a minor involvement of GE junction or distal esophagus
• Locally advanced and considered surgically unresectable or metastatic
• Measurable disease

• Accurately measured in at least 1 dimension as at least 20 mm with conventional techniques or at least 10 mm with spiral CT scan
• No truly nonmeasurable lesions only:

• Bone lesions
• Leptomeningeal disease
• Ascites
• Pleural/pericardial effusions
• Inflammatory breast disease
• Lymphangitis cutis/pulmonis
• Abdominal masses not confirmed and followed by imaging techniques
• Cystic lesions
• No brain metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 70-100%

Life expectancy:

• Not specified

Hematopoietic:

• Granulocyte count at least 1,500/mm^3
• Platelet count at least 150,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 mg/dL

Renal:

• Creatinine no greater than 1.5 mg/dL

Cardiovascular:

• No history of active angina
• No myocardial infarction within the past 6 months
• No history of significant ventricular arrhythmia requiring medication with antiarrhythmics
• Well-controlled atrial fibrillation on standard management allowed

Pulmonary:

• DLCO at least 60%

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 2 months after study participation
• No preexisting neurotoxicity of grade 3 or greater
• No serious concurrent infection or nonmalignant medical illness that is uncontrolled or whose control may be jeopardized by complications of study therapy
• No concurrent psychiatric disorders that would preclude study compliance
• No other active malignancy within the past 5 years except:

• Nonmelanoma skin cancer
• Carcinoma in situ of the cervix
• History of T1a or b prostate cancer (detected incidentally at transurethral resection of prostate [TURP] and comprising less than 5% of resected tissue) provided prostate-specific antigen remained normal since TURP removal
• HIV negative
• No other concurrent medical condition that would preclude study therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent immunotherapy

Chemotherapy:

• Recovered from prior chemotherapy
• No more than 1 prior neoadjuvant or adjuvant regimen for esophageal cancer
• No prior taxanes for esophageal cancer
• No prior bryostatin 1 for esophageal cancer
• No other concurrent chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• Prior radiotherapy allowed provided recent evidence of disease progression if indicator lesion is within prior radiation field
• Recovered from prior radiotherapy
• No concurrent radiotherapy

Surgery:

• Not specified