Irofulven in Treating Patients With Relapsed or Refractory Non-small Cell Lung Cancer

OBJECTIVES: I. Determine the response rate to 6-hydroxymethylacylfulvene (HMAF) as salvage
chemotherapy in patients with relapsed or refractory non-small cell lung cancer. II.
Determine the duration of response to this regimen in this patient population. III.
Determine the effect of prior response to chemotherapy on the response to HMAF in these
patients. IV. Determine the survival and failure-free survival of patients treated with
HMAF. V. Evaluate the toxicity profile of HMAF as salvage therapy in these patients.

OUTLINE: Patients are stratified into relapsed or refractory patient groups based on results
achieved with prior therapy. Patients receive 6-hydroxymethylacylfulvene IV over 5 minutes
daily for 5 days. Courses repeat every 28 days. Patients with stable or responding disease
are treated for a minimum of 6 courses (2 courses beyond optimal response) in the absence of
unacceptable toxic effects or disease progression. Patients are followed at least every 3
months for 1 year, then every 6 months until death.

PROJECTED ACCRUAL: A total of 66 patients (33 for each stratum) will be accrued for this
study within 12-18 months.

DISEASE CHARACTERISTICS: Histologically or cytologically proven recurrent or refractory
non-small cell lung cancer Squamous cell Adenocarcinoma (including bronchoalveolar cell)
Large cell anaplastic (giant and clear cell carcinomas) Measurable disease (not bone
disease only, pleural or pericardial effusions, or irradiated lesions, unless progression
is documented after radiotherapy) No CNS metastases

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-1 Life expectancy:
Not specified Hematopoietic: Granulocyte count at least 1,500/mm3 Platelet count at least
100,000/mm3 Hepatic: Bilirubin no greater 1.5 mg/dL SGOT no greater than 2 times upper
limit of normal (ULN) Renal: Creatinine no greater than ULN Cardiovascular: No active
cardiac disease No unstable angina No myocardial infarction within 6 months No congestive
heart failure No inability to tolerate hypotension Other: Not pregnant or nursing Fertile
patients must use effective contraception HIV negative No uncontrolled diabetes mellitus
No psychiatric disorders No concurrent secondary malignancies except nonmelanomatous skin
cancer or patients with less than a 30% risk of relapse

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: At least 4 weeks
since prior chemotherapy (6 weeks since mitomycin) At least 1 prior chemotherapy agent or
combination, including adjuvant or neoadjuvant therapy for non-small cell lung cancer No
more than 1 prior chemotherapy agent or combination for metastatic or recurrent disease No
prior HMAF No other concurrent chemotherapy Endocrine therapy: No concurrent hormonal
therapy except for nondisease related conditions Radiotherapy: See Disease Characteristics
At least 4 weeks since prior radiotherapy No concurrent palliative radiotherapy Surgery:
Not specified