Flavopiridol and Paclitaxel in Treating Patients With Locally Advanced or Metastatic Esophageal Cancer That Has Not Responded to Previous Paclitaxel

OBJECTIVES:

• Determine the response rate in patients with paclitaxel-refractory locally advanced or metastatic esophageal cancer treated with sequential paclitaxel and flavopiridol.
• Determine the toxicity of this regimen in these patients.
• Assess the quality of life of patients treated with this regimen.
• Obtain pharmacokinetic information about this regimen.

OUTLINE: This is a multicenter study.

Patients receive paclitaxel IV over 3 hours on day 1 and flavopiridol IV continuously over 24 hours on day 2 weekly for 3 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

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

PROJECTED ACCRUAL: A total of 12-37 patients will be accrued for this study within 6-18 months.

DISEASE CHARACTERISTICS:

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

• If tumor extends below the GE junction into the proximal stomach, 50% of the tumor must involve the esophagus or GE junction
• No gastric cancers with only a minor involvement of the GE junction or distal esophagus
• Metastatic or locally advanced disease that is considered surgically unresectable
• Must have failed a prior chemotherapy regimen that included paclitaxel for metastatic disease OR
• Failed prior combination taxane-based chemotherapy and radiotherapy for locally advanced disease

• Must have documented evidence of the following:

• Disease progression while on taxane-based neoadjuvant or adjuvant therapy OR
• Recurrent disease within 6 months of therapy
• Measurable disease

• Accurately measured in at least 1 dimension

• At least 20 mm by conventional techniques OR
• At least 10 mm by spiral CT scan
• The following are considered nonmeasurable:

• Bone lesions
• Leptomeningeal disease
• Ascites
• Pleural/pericardial effusions
• Inflammatory breast disease
• Lymphangitis cutis/pulmonis
• Abdominal masses that are 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:

• Absolute 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 active angina or myocardial infarction within the past 6 months
• No significant ventricular arrhythmia requiring antiarrhythmic medication
• Atrial fibrillation that is well controlled on standard management allowed

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 2 months after study
• No preexisting peripheral neuropathy of grade 2 or greater
• No serious concurrent infection
• No uncontrolled, nonmalignant medical illness that would preclude study
• HIV negative
• No other active malignancy within the past 5 years except:
• Nonmelanoma skin cancer or
• Carcinoma in situ of the cervix
• History of T1a or T1b prostate cancer (detected incidentally during transurethral resection of the prostate and comprising less than 5% of resected tissue) allowed if PSA normal since surgery
• No medical or psychiatric condition that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent immunotherapy

Chemotherapy:

• See Disease Characteristics
• No more than 6 months since prior paclitaxel
• No other concurrent chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• Prior radiotherapy allowed (indicator lesion must be outside of prior radiation port unless recent evidence of disease progression at that site)
• No concurrent radiotherapy

Surgery:

• See Disease Characteristics

Other:

• No prior cyclin-dependent kinase or protein kinase C inhibitors for esophageal cancer
• Recovered from toxic effects of any prior therapy
• No concurrent vitamins, antioxidants or herbal preparations or supplements