Experience with ifosfamide combinations in malignant lymphomas

Results of a salvage combination regimen, MIME (methyl-glyoxal-bis-guanylhydrazone [methyl-GAG], ifosfamide, methotrexate, etoposide), as well as a front-line study, both containing ifosfamide, are described. The MIME regimen is associated with an overall response rate of 60% and a complete response (CR) rate of 24% in 208 patients. Twenty-five percent of complete responders with aggressive lymphomas have had sustained remissions longer than 2 years. The long-term survival of the whole group of patients with intermediate-grade lymphoma is 15%. Complete responders with low-grade lymphoma, in contrast, show an initially favorable relapse pattern, but a plateau has not been observed in the relapse-free survival curve. In view of the activity observed with ifosfamide as a single agent, a front-line regimen was devised that was aimed at maximizing the CR rate by changing the chemotherapy according to the response obtained after every three courses. CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) was administered initially, and if CR was not obtained, a second regimen, HOAP-Bleo (doxorubicin, vincristine, cytarabine, prednisone, bleomycin), was given. Again if after three courses CR was not attained, IMVP-16 (ifosfamide, methotrexate, etoposide) was administered. The CR rate was 81% and the long-term survival (at 10 years) was 62%, which compares favorably with other third-generation regimens.