CODBLAM IV chemotherapy for large cell lymphoma: sequential use of infusional vincristine and bleomycin and "high dose" consolidation.

BACKGROUND: Based on prior results in large cell lymphoma (LCL) with COPBLAM (Cyclophosphamide, Oncovin, Prednisone, Bleomycin, Adriamycin, Matulane) I and COPBLAM III, CODBLAM (Cyclophosphamide, Oncovin, Dexamethasone, Bleomycin, Adriamycin, Matulane) IV was developed to intensify treatment further by utilizing four sequential cycles of infusional chemotherapy followed by high-dose chemotherapy and cycle active agents. METHODS: Sixty-one patients with LCL, mostly B-cell lymphoma, with 54% >60 years of age, were treated with daily continuous infusion of vincristine 1.0 mg/m2 days 1-2, bleomycin 4 mg/m2 i.v. push x 1 only followed by daily infusion 4 mg/m2 days 1-5, dexamethasone 10 mg/m2 days 1-5, procarbazine 100 mg/m2 orally days 1-5, doxorubicin 35 mg/m2 i.v. push day 1 (escalated), and cyclophosphamide 350 mg/m2 i.v. push day 1 (escalated), all given every 3 weeks for four cycles. After infusions, patients were restaged and treated with single courses of doxorubicin 90 mg/ m2 i.v. push followed at 3 weeks with cyclophosphamide 1500 mg/m2 i.v. push (both with concomitant vincristine 1 mg/m2 i.v. push and dexamethasone 10 mg/m2 p.o. daily for 5 days). Remaining treatment consisted of methotrexate 120 mg/m2 i.v. push with citrovorum rescue, cytarabine 250 mg/m2 i.v. push, and etoposide 100 mg/m2 i.v. infusion over 1 h, all given every 10 days for six cycles. RESULTS: The overall complete response (CR) rate was 88%. Of all patients, 36 (59%) are sustained disease free at a median follow-up time of 55 months. In patients age < or = 60 years, 89% achieved CR and 85% of patients age >60 years attained CR. CR was achieved in 83% of patients with constitutional B-type symptoms, 69% of patients with bulky adenopathy, and 86% of patients with immunoblastic histology. Toxicity was primarily pulmonary, occuring in 15% of patients. One toxic death was observed. CONCLUSIONS: Infusional CODBLAM IV may represent an effective and unique treatment for LCL.

COPBLAM III: infusional combination chemotherapy for diffuse large-cell lymphoma.

COPBLAM III, a polychemotherapy regimen consisting of cyclophosphamide, infusional vincristine, prednisone, infusional bleomycin, doxorubicin, and procarbazine, was administered to 51 patients with diffuse large-cell lymphoma. Ninety-six percent of patients age 60 or younger achieved a complete response (CR); none have relapsed. Overall, 88% of patients are alive and well and potentially in the survival plateau. For patients greater than 60 years, CR was obtained in 73%, with 42% potentially in the survival plateau, the difference resulting in part from four relapses, three toxic deaths, and one presumed unrelated death. These results in the elderly were paralleled by a relatively reduced ability to tolerate therapy. Toxicity was primarily pulmonary, occurring in 39% of patients, two of whom died. With an overall CR rate of 84%, of which 92% are sustained at a median follow-up of 40 months, COPBLAM III represents a highly effective treatment in a sizeable cohort of patients.