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