Etoposide in Treating Patients With Relapsed Non-Hodgkin's Lymphoma

OBJECTIVES: I. Evaluate the response rate and response duration in patients with relapsed
non-Hodgkin's lymphoma when treated with daily oral etoposide. II. Describe the toxic
effects of daily oral etoposide in these patients. III. Monitor etoposide trough levels and
determine whether etoposide concentrations correlate with age, response, and toxicity.

OUTLINE: Patients receive oral etoposide daily for 21 days. Treatment is repeated every 28
days in the absence of disease progression or unacceptable toxicity. Patients in complete or
partial remission receive 2 courses past best response (minimum 6 courses). Patients with
stable disease after 3 courses may be removed from study. Patients are followed every 6
months for 2 years, then annually for survival.

PROJECTED ACCRUAL: Approximately 97 patients will be accrued for this study over 2 years.

DISEASE CHARACTERISTICS: Histologically documented non-Hodgkin's lymphoma Needle or core
biopsy not acceptable as sole means of diagnosis No mantle cell or transformed lymphoma
One of the following International Working Formulation (IWF) histologic subtypes required:
Small lymphocytic with absolute lymphocytic count less than 5,000 (IWF A) Follicular,
predominately small cleaved cell (IWF B) Follicular, mixed (IWF C) Follicular, large cell
(IWF D) Diffuse, small cleaved cell (IWF E) Diffuse, mixed (IWF F) Diffuse, large cell
(IWF G) Large cell, immunoblastic (IWF H) Recurrent or refractory disease treated with no
more than 4 prior chemotherapy regimens Rebiopsy of a node at first relapse recommended
Prior etoposide (oral or intravenous) allowed if given for no more than 5 days every 3
weeks The following are considered 1 prior therapy each: Identical drugs given on 2
different schedules Bone marrow transplant preparative regimen (single cycle of
chemotherapy used solely to mobilize peripheral blood stem cells considered part of
preparative regimen) Ineligible for protocol CLB-9551 (aminocamptothecin) Measurable
disease by physical exam or imaging study required Indicator lesion larger than 1 x 1 cm
No prior radiotherapy to indicator lesion unless progression clearly documented The
following are not considered measurable: Barium study Ascites or pleural effusions Bony
disease Bone marrow involvement No known parenchymal or leptomeningeal CNS disease Lumbar
puncture not required prior to study

PATIENT CHARACTERISTICS: Age: Not specified Performance status: CALGB 0-2 Hematopoietic:
Absolute granulocyte count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic:
Bilirubin no greater than 1.5 times normal Renal: Creatinine no greater than 1.5 times
normal Other: HIV negative (testing required for patients at risk) No uncontrolled
infection No other serious medical condition that would interfere with evaluation of study
agent No psychiatric condition that would preclude protocol completion or informed consent
No second malignancy within 5 years except curatively treated: Basal cell skin cancer
Cervical cancer Not pregnant or nursing Adequate contraception required of fertile
patients

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease
Characteristics At least 3 weeks since prior chemotherapy (3 weeks for nitrosoureas,
melphalan, or mitomycin) Endocrine therapy: No concurrent corticosteroids except for
physiologic replacement Radiotherapy: At least 3 weeks since prior radiotherapy Surgery:
Not specified Other: No other concurrent investigational agent