A PHASE-II TRIAL OF PREDNISONE, ORAL ETOPOSIDE, AND NOVANTRONE (PEN) AS INITIAL TREATMENT OF NON-HODGKINS-LYMPHOMA IN ELDERLY PATIENTS

This phase II study was designed to improve the outcome of elderly pat ients with advanced aggressive non-Hodgkin's lymphomas (NHL's) by empl oying a novel chemotherapy regimen PEN (prednisone, oral etoposide and mitoxantrone), as initial treatment. Between July 1991 and September 1993, 43 patients (14 male, 29 female) aged 66-82 years (median 74) re ceived 1-8 (median 4) courses of PEN (total 192) q28 days (prednisone 50 mg od x 14 days, oral etoposide 50 mg od x 14 days and mitoxantrone 8 mg/m(2) i,v, day 1) in the ambulatory setting. Pathologies of patie nts' tumors classified by the Working Formulation (WF) included C = 4, D = 2, E = 1, F = 7, G = 25, H = 4. Eighteen patients (42%) had stage IV, 15 (35%) stage III, 9 (21%) stage II and 1 (2%) stage I disease. Nineteen patients (44%) had B symptoms, 7 (16%) primarily extranodal d isease and 15 (35%) bone marrow involvement. Patients with congestive heart failure, current anti-failure medication or pretreatment Muga le ft ventricular ejection fraction (LVEF) of <45% (median pretreatment 6 0%) were excluded from PEN. After a median follow-up of 8.5 months (ra nge 1-30), 14 of 33 evaluable patients (42%) have achieved CR of their disease for 8+ months (range 4-19) and 6 (18%) PR for 6+ months (rang e 5-10), giving an overall response rate of 61%. Ten (30%) patients di d not respond to PEN and 10 were not evaluable for response. Response to PEN was not predicted by any pretreatment characteristic. Twenty si x patients enrolled on study are alive, The estimated median survival is 26 months and the predicted survival at 2 years is 58% (Kapian-Meie r). Myelosuppression was the dose limiting toxicity of PEN. World Heal th Organization (WHO) grade > = 3 neutropenia (< 1.0 x 10(9)/L) occurr ed in 22 (51%) patients on at least one occasion and was associated wi th fever in 12(28%). However, only 8 (19%) patients had grade > = 3 ne utropenia for 2 consecutive weeks of a treatment cycle. Three patients (7%) died from treatment related neutropenic sepsis, Anemia and throm bocytopenia (WHO grade > = 3) occurred in 8 (19%) and 3 (7%) patients respectively. Cardiovascular events on study included 2 deep vein thro mboses, 3 pulmonary emboli (1 of whom died) and 2 episodes of congesti ve heart failure, Three patients (7%) developed an LVEF of < 45% on st udy. Other non-hematologic toxicities were minimal with only 2 patient s experiencing WHO grade > = 3 nausea, 3 stomatitis and 2 fatigue. In summary, PEN is an active, well-tolerated new regimen for use in elder ly patients with NHL's. It is particularly easy to administer on a onc e 4 weekly schedule in the ambulatory setting. Consideration should be given to a definitive phase III study of PEN versus CHOP with or with out hematopoietic growth factor support. Further study is merited due to the poor outcome and significant morbidity currently associated wit h the use of CHOP in elderly patients with NHL's.