Results of treatment with high intensity, brief duration chemotherapy in poor prognosis non‐hodgkin's lymphoma

A novel chemotherapeutic approach was designed for the treatment of intermediate and high‐grade histology non‐Hodgkin's lymphoma using augmented (but subtransplantation) doses of chemotherapy administered at frequent intervals in the inpatient setting. For the initial evaluation of this regimen, poor prognosis patients were treated with a projected long‐term survival rate of less than 25% in response to standard therapy. Between March 1982 and May 1988, 56 previously untreated patients were entered into this study; all patients had either high‐grade histology (20 patients) or predominantly large cell lymphoma (36 patients). Median age was 41.5 years (range, 18 to 69 years). Poor prognosis features included: Stage IV, 71%; poor performance status (Eastern Cooperative Oncology Group scale, 2 to 4), 55%; multiple extranodal sites of disease, 52%; elevated lactic dehydrogenase (> 300 IU/I), 43%; and bulky (> 10 cm) tumor masses, 30%. Thirty‐three of 56 patients (59%) were in Shipp's Category 3. During the 6‐year study, the chemotherapy regimen was modified in an attempt to improve efficacy and reduce toxicity. However, most patients received a 2‐month course of therapy as follows: cyclophosphamide 1500 mg/m² intravenously (IV) on days 1, 2, and 29; etoposide 400 mg/m² IV on days 1, 2, and 3 and 100 mg/m² on days 29, 30, 31; doxorubicin 45 mg/m² IV on days 29, 30; vincristine 1.4 mg/m² IV on days 8, 22, 36, and 50; bleomycin 10 units/m² IV on days 8, 22, 36, and 50; methotrexate 200 mg/m² IV on days 15 and 43 followed 24 hours later by leucovorin 15 mg/m² IV every 6 hours for six doses; and prednisone 60 mg/m² orally on days 1 to 7 and 29 to 35. The complete response (CR) rate was 77% (95% confidence interval, 64% to 86%). There were ten relapses, only one of which occurred after 18 months of follow‐up. Overall event‐free survival (EFS) was 52% (95% confidence interval, 36% to 68%), with a median follow‐up of 36 months. Eleven of 13 patients with small noncleaved lymphoma had CR; actuarial EFS in this subgroup was 61%. Myelosuppression occurred in all patients, with severe leukopenia (< 1000/μl) lasting a median of 12 days (range, 3 to 29 days); toxic deaths occurred in five patients (9%; 95% confidence interval, 4% to 19%). This intensive approach improved the response and survival of very poor risk non‐Hodgkin's lymphoma patients.