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 refractory lymphoma. To evaluate response and its duration after administration of intravenous Etoposide, methylprednisolone, high-dose cytosine arabinoside, and cisplatin (ESHAP) as consolidation therapy after complete or partial responses (CR or PR, respectively) or after crossover therapy for progressive disease. Methods: Patients received MINE(o) consisting of mesna, 1.33 g/m² infused over 1 hour daily × 3 followed 4 hours later by oral mesna at 500 mg; ifosfamide, 1.33 g/m² infused over 1 hour daily × 3; mitoxantrone, 8 mg/m² intravenously on day 1, and oral VP-16, 30 mg/m² daily × 13. The ESHAP regimen consisted of intravenous VP-16, 40 mg/m² infused over 2 hours daily × 4; methylprednisolone, 500 mg intravenously daily × 4; cytosine arabinoside, 1.5 g/m² infused over 3 hours on day 4; and cisplatin, 25 mg/m² given as a continuous 24-hour infusion daily × 4. Statistical analysis was performed using the 2-stage design described by Simon. For the oral VP-16 regimen to be of interest, at least 36% patients had to achieve a complete remission. Results: The overall response rate achieved with MINE(o) was 40% (15% CR, 25% PR). Seven patients with prior exposure to cytosine arabinoside and cisplatin (AP) received MINE(o) alone of whom only one achieved a response (CR). Thirteen patients without prior exposure to AP received consolidation (2 patients) or crossover (11 patients) therapy with ESHAP. Crossover therapy with ESHAP further improved the response in only two of five patients with partial response to MINE(o) and none of six patients who failed MINE(o). Median response 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 therapy with ESHAP did not further improve the response rate. The duration of response after MINE(o)/ESHAP was short.