COPBLAM: Infusion Chemotherapy for Large Cell Lymphoma

Early in 1977, a new combination chemotherapy program was initiated at the New York Hospital-Cornell Medical Center for large cell lymphoma (LCL). This program, known as COPBLAM: {cyclophosphamide, Oncovin, (vincristine), prednisone, bleomycin, Adriamycin, Matulane (procarbazine)} was an intensive multidrug regimen designed to maximize tumor cell kill1. Unique to this treatment for LCL was the incorporation of then novel concepts and features which were as follows: 1)Dosage escalation provisions for two major drug components (cyclo-phosphamide, Adriamycin) appropriate to patient tolerance, thereby allowing fullest implementation of these agents. Protocols in the past had provided dosage reduction schedules when treatment proved too intense, but few had ever contained provisions for increasing treatment intensity, notwithstanding the steep dose-response relationship of these drugs2.2)Treatment cycles of 21 days, in contrast to the customary monthly schedules used in the past. Toxicity from both cyclophosphamide and Adriamycin is usually ameliorated in this interval, and shorter cycles provided for further intensification of treatment2.3)The use of six drugs rather than the customary four or five, all putatively non-cross-resistant with differing mechanisms of action. Procarbazine was added to the standard BACOP (bleomycin, Adriamycin, cyclophosphamide, Oncovin, prednisone) combination because of its ability to cross the blood brain barrier. Its previous incorporation in the COP (cyclophosphamide, Oncovin, prednisone) regimen to form the C-MOPP (cyclophosphamide, Oncovin, procarbazine, prednisone) program greatly augmented the cure rate3.4)The fuller use of nonmyelosuppressive agents, particularly vin-cristine, prednisone and bleomycin, of which the latter was given at day 14, allowing further tumor treatment in the face of nadir blood counts.