The Treatment of Elderly Patients with Aggressive Non-Hodgkin's Lymphomas: Feasibility and Efficacy of an Intensive Multidrug Regimen

Abstract

The results of a prospective trial of an 8 week treatment for elderly patients with advanced intermediate-high grade NHL are reported. Our aim was to reduce general toxicity without losing an antilymphoma effect. For this reason the use of growth factor was studied. We also analysed the behavior of different histological groups (E + F vs G + H). From November 1991 to November 1993 100 patients older than 65 years with combination intermediate-high grade advanced stage NHL were treated with the P-VEBEC regimen, an original including epirubicin 50 mg/sqm, cyclophosphamide 300 mg/sqm and etoposide 100 mg/sqm on weeks 1, 3, 5, 7; vinblastine 5 mg/sqm and bleomycin 5 mg/sqm on weeks 2, 4, 6, 8; prednisone 50 mg/sqm/day per os in the first two weeks and thereafter every other day .46 pts received rG-CSF 5 micrograms/Kg/day throughout the treatment starting on day 2 of every week for 4 consecutive days. Twenty eight pts had B symptoms, 41 had bulky disease, 37 LDH levels above normal, 50 stage IV patients and 30 had bone marrow involvement. Sixty two percent achieved a complete remission (CR). Adverse prognostic factors for CR were E and F histology, stage IV disease, bone marrow infiltration, serum LDH levels above normal, international Prognostic Index (I.I.) intermediate-high and high risk categories and relative dose intensity (RDI) less than 0.80. Severe toxicity was rarely recorded and only one toxic death was observed. With a median follow-up of 33 months OS, DFS and EFS were 44%, 60% and 30% respectively. EFS was influenced by stage, BM involvement, level of LDH and I.I. intermediate-high and high risks. The 52 patients with DLCL (diffuse large cell lymphomas--G + H according to WF) did better with a higher CR, OS, DFS and EFS rates, than the other WF subtypes. In conclusion P-VEBEC is a feasible combination to use in elderly patients, mainly in DLCL. The use of rG-CSF improves the RDI. A RDI > 0.80 could play a role in improving the outcome, especially in patients with adverse prognostic factors. For other subgroups another schedule is probably justified.

Are prophylactic haematopoietic growth factors of value in the management of patients with aggressive non-Hodgkin's lymphoma?

“…h Including the nonrandomised trial by Bertini et al (1996). Aviles et al (1994) 1.47 (0.69 -3.10) Bertini et al (1996) 0.91 (0.55 -1.50) Fridik et al (1997) 1.14 (0.67 -1.97) 1.16 (0.66 -2.04), 5 years Gisselbrecht et al (1997) 0 Bertini et al (1996).…”

“…Our simple cost-effectiveness analysis, based on direct costs alone, suggests that using G-CSF as a primary prophylaxis for Table 2 The relative risk (or ratio) in relation to specified outcomes, comparing the rate in the G-CSF group with the rate in the non-G-CSF group Defined as -ANCo0.5 Â 10 9 l À1 and fever X37.51C (Pettengell); severity score 2 -4 (Gerhartz et al, 1993); not specified (Aviles et al, 1994); Xgrade 3 (Bertini et al, 1996); described as 'documented infection' (Fridik et al, 1997); Xgrade 2 (Gisselbrecht et al, 1997); described as 'clinically relevant' (Zinzani et al, 1997). The ratio of the mean number of days in hospital in the G-CSF group to the mean in the non-G-CSF group.…”

“…f Excluding the nonrandomised trial by Bertini et al (1996). Excluding the trial by Aviles et al (1994) because the results were based on number of cycles, not patients.…”

“…The analyses presented here were based on the six randomised controlled trials (Pettengell et al, 1992;Gerhartz et al, 1993;Aviles et al, 1994;Fridik et al, 1997;Gisselbrecht et al, 1997;Zinzani et al, 1997) and one nonrandomised trial (Bertini et al, 1996), which assessed the use of HGF in patients with aggressive NHL who had not been treated previously. All but one trial used granulocyte colony-stimulating factor (G-CSF), the other trial used granulocyte-macrophage-CSF (GM-CSF) (Gerhartz et al, 1993).…”

“…All but one trial used granulocyte colony-stimulating factor (G-CSF), the other trial used granulocyte-macrophage-CSF (GM-CSF) (Gerhartz et al, 1993). The dose was specified as 5 mg kg day À1 in five trials (Aviles et al, 1994;Bertini et al, 1996;Fridik et al, 1997;Gisselbrecht et al, 1997;Zinzani et al, 1997), 5.6 mg kg day À1 in one trial (Gerhartz et al, 1993) and 230 mg m À2 in another trial (Pettengell et al, 1992). Information on the following outcomes were obtained for each treatment group from each published report, where available: the incidence of severe neutropenia (neutrophil count o0.5 Â 10 9 l À1 ) the incidence of severe or clinically important infections.…”