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

We have previously reported that combination chemotherapy based on the drugs cytarabine/platinum is effective in recurring lymphomas. In this phase II study, we prospectively studied a combination regimen of mesna/ifosfamide, mitoxantrone and etoposide (MINE) in patients with recurring lymphoma who had already received cytarabine/platinum but did not respond to the treatment.

48 patients received MINE at the following doses: mesna 1.33 g/m2 i.v. daily x 3, and 500 mg p.o. daily 4 hours after each i.v. dose; ifosfamide 1.33 g/m2 i.v. daily, given concurrently with mesna, x 3 d; mitoxantrone 8 mg/m2 i.v. on day 1; and etoposide 65 mg/m2 i.v. daily x 3. Treatment cycles were 21-28 days apart, depending on patients' blood counts, with a maximum number of 6 cycles in responding patients. The histologic grade of the lymphomas according to the Working Formulation was low in 8 patients and intermediate in 40 patients. In the latter group, 12 were transformed from low grade.

Overall, 48% of the patients responded, with 21% having a complete response (CR), and 27% having a partial response (PR). The median survival time was 9 months, and the median follow-up of survivors is 51 months at this writing. Median time to treatment failure was 12 months for patients with complete responses, and 5 months for patients with partial responses. The most serious complication was myelosuppression, with 2 deaths resulting from neutropenic infection.

The MINE regimen induced responses in a moderate fraction of patients after their prior exposure to cytarabine/platinum salvage therapy, indicating there is no absolute cross resistance between these drug regimens.