European experience with ifosfamide in lymphomas

In malignant lymphomas, ifosfamide-containing regimens were at first used mainly in second-line therapy and response-adapted protocols. Currently, in combination with other drugs, ifosfamide is being used in several phase-III trials. As salvage therapy in non-Hodgkin's lymphoma (NHL), IMV-Bleo (ifosfamide, methotrexate, etoposide, bleomycin) produced a complete remission (CR) rate of 41% and seemed to be particularly effective in patients with suboptimal response to first-line treatment. IBEP (ifosfamide, bleomycin, etoposide, procarbazine), in combination with procarbazine and bleomycin was an effective non-cross-resistant alternative in CHOP (cyclophosphamide, hydroxydauomycin/doxorubicin, vincristine, prednisone)-refractory NHL. In a trial of response-oriented therapy in high-grade malignant lymphoma patients, the investigators concluded that consolidation therapy was necessary even in patients with rapid response to CHOP. Patients with NHL resistant to or relapsing from conventional chemotherapy or with MOPP-ABVD (mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine, decarbazine)-resistant Hodgkin's disease (HD) were treated with BMV-VIP [bleomycin, plus high-dose methylprednisolone plus ifosfamide, etoposide, plus methylprednisolone]. In high-grade malignant NHL, patients received three cycles of COP-BLAM (cyclophosphamide, vincristine, procarbazine, prednisone, bleomycin, doxorubicin). Those who achieved CR received two more cycles of COP-BLAM and IMV (ifosfamide, methotrexate, etoposide) as consolidation therapy. Patients in partial remission (PR) or with less of a response to COP-BLAM were switched to IMV. After reaching CR, patients received two additional cycles as consolidation therapy. After the second restaging, patients were randomized to observation v additional radiotherapy. Of 191 patients, 148 have passed first restaging with 51% in CR; 85 went through the second restaging with 61% in CR. Of 32 patients who only reached PR after the first restaging, 15 (47%) achieved CR with IMV. For primary treatment of HD, the German Hodgkin Study Group added a third non-cross-resistant regimen, IMEP (ifosfamide, methotrexate, etoposide, prednisone), to supplement COPP (cyclophosphamide, vincristine, procarbazine, prednisone) and ABV in the primary treatment of HD. In a pilot study, 87% of 63 evaluable patients reached CR. The current phase-III protocol is comparing COPP/ABVD with fast alternating cycles of COPP/ABV/IMEP.