A PHASE-II TRIAL OF ORAL ETOPOSIDE WITH MITOXANTRONE AND IFOSFAMIDE MESNA CONSOLIDATED WITH INTRAVENOUS ETOPOSIDE, METHYLPREDNISOLONE, HIGH-DOSE ARABINOSIDE, AND CISPLATIN AS SALVAGE THERAPY FOR RELAPSING AND OR REFRACTORY LYMPHOMAS/

Purpose: To evaluate the response to oral Etoposide when combined with mesna,ifosfamide, and mitoxantrone in patients with relapsed and/or r efractory lymphoma. To evaluate response and its duration after admini stration of intravenous Etoposide, methylprednisolone, high-dose cytos ine arabinoside, and cisplatin (ESHAP) as consolidation therapy after complete or partial responses (CR or PR, respectively) or after crosso ver therapy for progressive disease. Methods: Patients received MINE(o ) consisting of mesna, 1.33 g/m(2) infused over 1 hour daily x 3 follo wed 4 hours later by oral mesna at 500 mg; ifosfamide, 1.33 g/m(2) inf used over 1 hour daily x 3; mitoxantrone, 8 mg/m(2) intravenously on d ay 1, and oral VP-16, 30 mg/m(2) daily x 13. The ESHAP regimen consist ed of intravenous VP-16, 40 mg/m(2) infused over 2 hours daily x 4; me thylprednisolone, 500 mg intravenously daily x 4; cytosine arabinoside , 1.5 g/m(2) infused over 3 hours on day 4; and cisplatin, 25 mg/m(2) given as a continuous 24-hour infusion daily x 4. Statistical analysis was performed using the 2-stage design described by Simon. For the or al VP-16 regimen to be of interest, at least 36% patients had to achie ve a complete remission. Results: The overall response rate achieved w ith MINE(o) was 40% (15% CR, 25% PR). Seven patients with prior exposu re to cytosine arabinoside and cisplatin (AP) received MINE(o) alone o f whom only one achieved a response (CR). Thirteen patients without pr ior exposure to AP received consolidation (2 patients) or crossover (1 1 patients) therapy with ESHAP. Crossover therapy with ESHAP further i mproved the response in only two of five patients with partial respons e to MINE(o) and none of six patients who failed MINE(o). Median respo nse duration for the patients who received MINE(o)/ESHAP was 12 weeks (range, 4-55 weeks). Conclusions: Oral VP-16 combined with ifosfamide/ mesna and mitoxantrone at the doses and schedules indicated has little activity against relapsed and/or refractory lymphomas. Crossover ther apy with ESHAP did not further improve the response rate. The duration of response after MINE(o)/ESHAP was short.