Advances in Chemotherapy for Large Cell Lymphoma

Three generations of chemotherapy regimens for the treatment of aggressive lymphomas have evolved in the past decade. The first-generation combination regimen, CVP, also known as COP (cyclophosphamide, vincristine, prednisone), produced maximum long-term survivals in considerably less than 20% of patients. With the MOPP (mechlorethamine, vincristine, procarbazine, prednisone) regimen, 40% of patients achieved complete remission (CR). This signal study was paralleled by other first-generation studies including CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), HOP (doxorubicin, vincristine, prednisone), CHOP-Bleo/BACOP (CHOP plus bleomycin), and COMLA (cyclophosphamide, vincristine, methotrexate, leucovorin, cytarabine). None of the regimens was shown to be particularly superior to the others. Survival plateaus were seen in approximately 20% to 40% of patients. Second-generation therapies, COP-BLAM (cyclophosphamide, vincristine, prednisone, bleomycin, doxorubicin, procarbazine), ProMACE-MOPP (prednisone, methotrexate, doxorubicin, cyclophosphamide, etoposide, mechlorethamine, vincristine, procarbazine, prednisone), M-BACOD (methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, dexamethasone), and m-BACOD (same as M-BACOD, but with a moderate dose of methotrexate and modified leucovorin given on days 8 and 15 instead of just day 10) were characterized by an increasing number of drugs, more frequent administration of myelosuppressive agents, and flexible dose schedules. This new treatment intensity resulted in CRs in excess of 70%. The third generation regimens have been characterized by innovative concepts of chemotherapy, including alternative modes of drug administration, greater use of marrow-sparing, cycle-active, and/or putatively non-cross-resistant agents, and more frequent and/or intense dose administration. These regimens, COP-BLAM III, MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin), ProMACE-CytaBOM (ProMACE plus cytarabine, bleomycin, vincristine, methotrexate), and high-dose doxorubicin with cytarabine, have produced over 80% CRs and survival plateaus in excess of 60%. In the COP-BLAM III regimen, 84% of patients achieved a pathologic CR. Overall, 65% of patients are alive, well, and free of disease, and potentially in the survival plateau. COD-BLAM IV (same as COP-BLAM, except dexamethasone is substituted for prednisone) is a new program that further intensifies treatment by using sequential, rather than alternate-cycle, infusions of bleomycin and vincristine. Results are still preliminary, with a short median follow-up of 19 months.(ABSTRACT TRUNCATED AT 400 WORDS)