A phase II trial of mesna/ifosfamide, mitoxantrone and etoposide for refractory lymphomas

BACKGROUND: We have previously reported that combination chemotherapy basedon the drugs cytarabine/platinum is effective in recurring lymphomas.In this phase II study, we prospectively studied a combinationregimen of mesna/ifosfamide, mitoxantrone and etoposide (MINE)in patients with recurring lymphoma who had already receivedcytarabine/ platinum but did not respond to the treatment. PATIENTS AND METHODS: 48 patients received MINE at the following doses: mesna 1.33g/m² IV daily x3, and 500 mg p.o. daily 4 hours after each IVdose; ifosfamide 1.33 g/m² IV daily, given concurrently withmesna, x3 d; mitoxantrone 8 mg/m² IV on day 1; and etoposide65 mg/m² IV daily x3. Treatment cycles were 21–28 daysapart, depending on patients' blood counts, with a maximum numberof 6 cycles in responding patients. The histologic grade ofthe lymphomas according to the Working Formulation was low in8 patients and intermediate in 40 patients. In the latter group,12 were transformed from low grade. RESULTS: Overall, 48% of the patients responded, with 21% having a completeresponse (CR), and 27% having a partial response (PR). The mediansurvival time was 9 months, and the median follow-up of survivorsis 51 months at this writing. Median time to treatment failurewas 12 months for patients with complete responses, and 5 monthsfor patients with partial responses. The most serious complicationwas myelosuppression, with 2 deaths resulting from neutropenicinfection. CONCLUSION: The MINE regimen induced responses in a moderate fraction ofpatients after their prior exposure to cytarabine/platinum salvagetherapy, indicating there is no absolute cross resistance betweenthese drug regimens. ifosfamide, salvage therapy, lymphoma