OBJECTIVES:

Primary

• Determine the dose-limiting toxicity and maximum tolerated dose of amrubicin when combined with irinotecan in patients with recurrent or relapsed extensive stage small cell lung cancer.

Secondary

• Determine the response rate in patients treated with this regimen.
• Determine the overall survival of patients treated with this regimen.
• Determine the frequency and severity of adverse events in patients treated with this regimen.

OUTLINE: This is a dose-escalation study of amrubicin.

Patients receive amrubicin on day 1 and irinotecan IV on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of up to 6 patients receive escalating doses of amrubicin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 1/3 (or 33%) of patients experience dose-limiting toxicity. An additional 6 patients are treated at the MTD.

PROJECTED ACCRUAL: A total of 6-30 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed small cell lung cancer

  • Extensive stage disease
• Recurrent or relapsed disease after 1-2 prior chemotherapy and/or radiotherapy regimens
• No unmanageable massive pleural effusion or pericardial effusion by chest CT scan
• No symptomatic brain metastasis

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• More than 3 months

Hematopoietic

• Absolute granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 8.5 g/dL

Hepatic

• ALT and AST ≤ 2 times upper limit of normal
• Bilirubin ≤ 1.5 mg/dL

Renal

• Creatinine normal

Cardiovascular

• No uncontrolled hypertension
• No unstable angina
• No congestive heart failure
• No myocardial infarction within the past year
• No ventricular arrhythmia requiring medical intervention
• No other serious cardiovascular disease

Pulmonary

• Arterial oxygen pressure (PaO_2) ≥ 70 torr
• No interstitial pneumonitis or pulmonary fibrosis by chest x-ray

Gastrointestinal

• No serious diarrhea
• No paralytic or obstructive ileus

Other

• Not pregnant or nursing
• No uncontrolled diabetes
• No severe infectious disorder

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• No prior anthracycline or its derivatives at > the upper dose limit (e.g., daunorubicin ≥ 25 mg/kg, doxorubicin ≥ 500 mg/m^2, or epirubicin ≥ 900 mg/m^2)

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics

Surgery

• Not specified