Comparison of two non-anthracycline-containing regimens for elderly patients with diffuse large-cell non Hodgkin's lymphoma - possible pitfalls in results reporting and interpretation

Age over 65 years is a risk factor per sa for doxorubicin administration, a nd coexisting diseases pose additional problems. There is still controversy whether chemotherapy regimens for elderly patients with aggressive NHL sho uld be fulldose doxorubicin containing or whether development of non-anthra cycline containing regimens is warranted. In this prospective study, 47 patients aged over 65 years with diffuse larg e cell NHL,clinical Stage I/IE bulky-IV and no other initial exclusion crit eria were randomized to receive either BCNU 120 mg/m(2) d. 1,VP16 60 mg/m(2 ) d. 2-4, procarbazine 85 mg/m2 d. 2-8 (arm A, 27 patients) or mitoxantrone 6 mg/m(2) d. 1. with VP16 and procarbazine in the same dosage and schedule (Arm B, 20 patients). Partial responders received additional irradiation t reatment if feasible. Arms were well balanced according to age, sex, clinic al stage and performance status. Ten patients from arm A and 13 from arm B had PS 2 or 3; 14 patients from arm A and 8 from arm B had clinically signi ficant antecedent and/or concomitant disease (SACD: cardiac, vascular, cere brovascular, neurological, renal or other). On the intent-to-treat basis, t he results were the following. ARM A: median number of cycles 3 (range id); early death 3 patients; 16/27 responses (59%), 7 complete: (30%). ARM B: m edian number of cycles 3 (range 1-6); early death 4 patients; 12/20 respons es 60%, 3 complete (15%). There was no difference either in response rate o r survival between the two arms, and pooled results from the two arms displ ayed a plateau on the survival curve from the 20-th mouth onwards on the pr obability level of 0.40. Clinical stage of NHL, bulky disease, age and sex did not influence survival. Initial performance status did influence surviv al at the significance level of p = 0.045. Although presence of SACD did no t influence initial performance status, it had a strong negative impact an survival (p = 0.0004). The results point to the existence of two prognostic categories of elderly patients with large cen NHL, one with a poor survival, the other achieving a significant response rate and relapse free survival. Comorbidity(SACD) ap parently accounts for the poor survival in a subpopulation of elderly patie nts. Clinical trials with elderly patients with NHL with PS 0 or 1 and no s erious coexisting disease as inclusion criteria, analyzed on an evaluable p atients basis, target only to a prognostically better subpopulation among t hese patients.