Topotecan and Vinorelbine in Treating Patients With Recurrent Lung Cancer

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of topotecan when combined with vinorelbine ditartrate in patients with recurrent lung cancer.

Secondary

• Assess the response and stable disease rates and the time to disease progression among treated patients.

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

Patents receive vinorelbine ditartrate IV over 8-10 minutes and topotecan IV over 30 minutes on days 1 and 8. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which ≥ 2 of 6 patients experience dose-limiting toxicity.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed lung cancer

• All histologic types eligible
• Recurrent or progressive disease after ≥ 1 prior chemotherapy regimen with or without radiotherapy

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) ≤ 2
• Karnofsky PS ≥ 60%
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Total bilirubin ≤ 1.5 mg/dL
• Creatinine ≤ 1.5 mg/dL
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other active invasive malignancy
• No uncontrolled illness including, but not limited to:

• Ongoing or active infection
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• No psychiatric illness/social situation that would limit compliance with study requirements
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to topotecan or vinorelbine ditartrate

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 2 weeks since prior radiotherapy
• No prior therapy with topotecan or vinorelbine ditartrate
• No chemotherapy within the past 4 weeks (6 weeks for nitrosoureas or mitomycin C)
• Recovered from agents administered > 4 weeks earlier
• No other concurrent investigational agents
• No concurrent palliative radiotherapy
• No other concurrent anticancer therapies or agents
• No concurrent hormones or other chemotherapy except for the following:

• Steroids for adrenal failure
• Hormones for nondisease-related conditions (e.g., insulin for diabetes)
• Intermittent dexamethasone as an antiemetic