A brief-duration combination chemotherapy for elderly patients with poor-prognosis non-Hodgkin's lymphoma

Abstract

Curative combination chemotherapy is available for many patients with aggressive non-Hodgkin's lymphoma (NHL); however, treatment of elderly patients with these regimens is difficult due to excessive toxicity. From 1983 to 1988 the authors treated 26 patients 65 years and older with aggressive NHL with a novel 8-week chemotherapy regimen containing bleomycin, etoposide, cyclophosphamide, doxorubicin, methotrexate with leucovorin, and prednisone (BECALM), designed to preserve dose intensity and minimize toxicity. Median age was 75 years. Histologic types included the following: 20 intermediate grade (16 large noncleaved cell; two large cleaved cell; one intermediate grade, unspecified); six high grade (four small noncleaved cell; one immunoblastic sarcoma B-cell; one high grade, unspecified), Twenty-one patients were Stage I11 or IV. Twenty-two of 26 patients had one or more of the following: tumor greater than 10 cm; multiple extranodal sites; lactate dehydrogenase (LDH) 400 IU/1 or greater; small noncleaved cell histologic type. Chemotherapy consisted of bleomycin 20 U intravenously (IV) weeks 1 and 7; etoposide 75 mg/m2 IV every day X 3 days on week 4; cyclophosphamide 600 mg/mz IV weeks 1 , 4 , 7 ; doxorubicin 40 mg/mz IV weeks 1 , 7 ; methotrexate 50 mg/mz IV weeks 1 , 2 , 4 , 5 , 7, 8 with oral leucovorin rescue; prednisone 60 mg orally for 10 days on weeks 1 , 4 , 7. Eighteen patients completed the 8-week treatment course. There were 13 complete responses (CR); seven patients remain in continuous CR at a median follow-up of 37.5 months. There have been five relapses, including one late relapse; and one patient died of an intercurrent illness in CR. Overall and actual event-free survivals are 38% and 27%, respectively. The major toxicities were neutropenic fever and mucositis. There were four treatment-related deaths. The authors conclude that BECALM chemotherapy can be administered to elderly patients with aggressive NHL. Although neurotoxicity and cumulative toxicity from bleomycin and anthracycline are avoided, the regimen remains moderately toxic, particularly with respect to myelosuppression. Treatment results compare favorably with other reported regimens in this group of patients with multiple poor prognostic features. Cancer 67:1487-1492,1991. ONSIDERABLE UNCERTAINTY exists regarding the C optimal approach to the treatment of non-Hodg-kin's lymphoma (NHL) in the elderly. Advances in therapy over the last 15 years have resulted in improved long-From the Division of Oncology and Hematology, Vanderbilt Uni

Mitoxantrone is superior to doxorubicin in a multiagent weekly regimen for patients older than 60 with high-grade lymphoma: results of a BNLI randomized trial of PAdriaCEBO versus PMitCEBO

“…Initiatives to improve cytotoxic delivery without compromising benefit have led investigators to develop weekly, multiagent chemotherapy regimens. [20][21][22][23]25,[36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55] Improvements in supportive care enable the delivery of chemotherapy at standard doses and intensity to deliver maximum benefit to patients. 56 The minimum age of entry of 60 was chosen because patients younger than this were eligible for high-dose regimens and because this age carried prognostic significance in the international prognostic index (IPI) analyses.…”

“…[14][15][16] During the 1980s, second-and third-generation combination chemotherapy regimens adapted for the elderly suggested similar outcomes with reduced toxicity in comparison to regimens for younger patients with similar histologies. [17][18][19][20][21][22][23][24][25] In the prednisolone, adriamycin, cyclophosphamide, etoposide, bleomycin, oncovin (vincristine), methotrexate (PACEBOM) alternating, weekly, combination chemotherapy regimen, the major toxicity problem was mucositis, which could be markedly reduced by the omission of methotrexate. 26 In this modified regimen, PAdriaCEBO, the greatest contributor to toxicity is adriamycin.…”

Complications of cytotoxic chemotherapy in older patients: focus on myelotoxicity in lymphomas

“…Recently, age-adapted treatment regimens, from the first to the third generation, have been designed and tested for their feasibility and efficacy in elderly aggressive-histology non-Hodgkin's lymphoma patients [16,[31][32][33][34][35][36][37][38][39][40]. In addition, progress has been made in defining maximally tolerated doses of the cytotoxic drugs and specifically testing anthracyclines with reduced cardiotoxicity [11,[41][42][43], as well as in investigating the advantages of applying hematopoietic growth factors in this older population.…”

Treatment of non-Hodgkin's lymphoma in the elderly: an update

“…McMaster et al 21 treated 26 patients with a novel 8-week chemotherapy regimen containing bleomycin, etoposide, cyclophosphamide, adriamycin, methotrexate with leucovorin and prednisone (BECALM). Eleven patients (42 per cent) achieved a CR and seven remain in continuous CR at a median follow-up of 37 months.…”