RATIONALE: Drugs used in chemotherapy, such as FR901228 and flavopiridol, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving FR901228 together with flavopiridol may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of FR901228 when given together with flavopiridol in treating patients with advanced lung, esophageal, or pleural cancer.

OBJECTIVES:

Primary

• Determine the maximum tolerated dose and dose-limiting toxic effects of FR901228 (depsipeptide) when administered with flavopiridol in patients with advanced primary lung or esophageal cancer, malignant pleural mesothelioma, or lung or pleural metastases.
• Determine the pharmacokinetics of this regimen in these patients.

Secondary

• Analyze gene expression in laser-captured tumor cells, buccal mucosa, and peripheral blood mononuclear cells of these patients before and after treatment with this regimen.
• Analyze mcl-1 protein expression and apoptosis in tumor biopsies from these patients before and after treatment with this regimen.

OUTLINE: This is a dose-escalation study of FR901228 (depsipeptide).

Patients receive FR901228 IV over 4 hours followed by flavopiridol IV continuously over 72 hours beginning on days 1 and 15. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of FR901228 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. Six additional patients receive treatment at the MTD.

PROJECTED ACCRUAL: A total of 48 patients will be accrued for this study within 1-2 years.

• Esophageal Cancer
• Lung Cancer
• Malignant Mesothelioma
• Metastatic Cancer

• Drug: alvocidib
• Drug: romidepsin

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed advanced malignancy of 1 of the following types:

  • Primary small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC)

    • No limited-stage SCLC or operable NSCLC

  • Esophageal cancer

    • Inoperable disease
  • Malignant pleural mesothelioma
  • Epithelial thymoma

  • Cancer of nonthoracic origin with metastases to the lungs or pleura

    • No potentially treatable pulmonary metastases from lymphomas or germ cell tumors
• Tumor must be amenable to biopsy by endoscopic or percutaneous fine needle aspiration techniques
• Chemonaïve patients allowed provided they refused potentially effective first-line chemotherapy

• Intracranial or leptomeningeal metastases allowed provided the following are true:

  • Treated by surgery or radiotherapy
  • No evidence of active disease
  • No requirement for anticonvulsant therapy or steroids

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 3 months

Hematopoietic

• Platelet count > 100,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3 (transfusion and cytokine independent)

Hepatic

• PT normal
• Bilirubin < 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 1.5 times ULN

Renal

• Creatinine ≤ 1.6 mg/dL OR
• Creatinine clearance > 70 mL/min

Cardiovascular

• No myocardial infarction within the past 6 months
• Ejection fraction ≥ 45%
• QTc ≤ 500 msec
• No unstable angina
• No cardiac ischemia
• No left ventricular hypertrophy
• No deep venous thrombosis requiring anticoagulation within the past 6 months

• No known cardiac abnormalities including any of the following:

  • Uncontrolled arrhythmias
  • History of sustained ventricular tachycardia, ventricular fibrillation, Torsades de Pointes, or cardiac arrest without an automatic implantable cardioverter defibrillator in place
  • Congenital long QT syndrome or QTc > 480 msec
  • Mobitz II second degree block without a pacemaker in place

  • Any cardiac arrhythmia requiring antiarrhythmic medication

    • Beta blockers and calcium channel blockers allowed
  • New York Heart Association class II or IV decompensated heart failure
  • Left ventricular ejection fraction < 50% by MUGA scan or echocardiogram
  • Hypertrophic or restrictive cardiomyopathy from prior treatment or other causes
  • Left ventricular hypertrophy
  • Uncontrolled hypertension (i.e., blood pressure ≥ 160/95)
  • Myocardial infarction within the past year
  • Clinically significant active myocardial ischemia by nuclear imaging or angiography
  • History of coronary artery disease (e.g., Canadian class II-IV angina or positive stress imaging study)

Pulmonary

• FEV_1 and DLCO > 30% of predicted
• pCO_2 < 50 mm Hg by arterial blood gas (ABG) on room air
• pO_2 > 60 mm Hg by ABG on room air
• No pulmonary embolism requiring anticoagulation within the past 6 months

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active infection
• HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 30 days since prior biologic therapy for the malignancy
• No concurrent cytokine support

Chemotherapy

• See Disease Characteristics
• Prior FR901228 (depsipeptide) or flavopiridol allowed provided patient did not experience dose-limiting toxicity at the dose they are scheduled to receive on study
• At least 30 days since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) for the malignancy

Endocrine therapy

• See Disease Characteristics

Radiotherapy

• See Disease Characteristics
• At least 30 days since prior radiotherapy for the malignancy
• At least 14 days since prior localized radiotherapy to non-target lesions and recovered

Surgery

• See Disease Characteristics

Other

• No more than 2 prior systemic cytotoxic treatment regimens
• No concurrent hydrochlorothiazide
• No concurrent digoxin