Source: DGNews  |  Posted 6 years ago

By Chris Berrie

LUGANO, SWITZERLAND -- June 10, 2005 -- The addition of a cisplatin, idarubicin, and prednisone (CIP) regimen as a consolidation therapy for the P-VABEC regimen remains safe and improves survival for elderly patients with diffuse large-cell lymphoma (DLCL), according to the long-term follow-up of a multicentre phase 2 trial.

The 8-cycle P-VABEC, delivered on an outpatient basis, consisted of weeks 1, 3, 5, and 7 administration of doxorubicin 30 mg/m[^]2[], cyclophosphamide 350 mg/m[^]2[], etoposide 100 mg/m[^]2[]; weeks 2, 4, 6, and 8 administration of vincristine 1.2 mg/m[^]2[], bleomycin 15 mg/td, with prednisone 50 mg/td.

Maurizio Martelli, MD, haematology researcher and principal investigator, haematology, University of Rome "La Sapienza," Rome, Italy, reported the findings here June 8[^]th[] on behalf of the Italian Cooperative Study Group at the 9[^]th[] International Conference on Malignant Lymphoma (ICML).

"In our previous study [Martelli et al. Ann. Oncol. 1999] we showed that P-VABEC is active for elderly patients, but with time, many of the patients relapsed," Dr. Martelli said. This new study was thus designed to improve on the progression-free survival (PFS) following the P-VABEC regimen in elderly patients through a reduction in relapse.

Of the 214 previously untreated elderly patients with DLCL who were registered from 1995 to 2000 (mean age, 70 years; range, 60-85 years), 107 were randomised at diagnosis to receive P-VABEC (male, 54%) and 95 to P-VABEC-CIP (male, 57%).

The subsequent CIP regimen consisted of cisplatin 40 mg/td on day 1, idarubicin 15 mg/m[^]2[] on day 8, and prednisone 50 mg/td on days 1 to 4 and 8 to 11. This 3-week cycle was repeated for 3 courses.

With no significant differences in the full range of patients' clinical characteristics between the 2 treatment arms, according to their age-adjusted International Prognostic Index (IPI) scores, 89 of the patients were considered as low risk (IPI, 0-1) and 113 as high risk (IPPI, 2-3).

Based on this intention-to-treat analysis, the 5-year overall survival (OS) and PFS were significantly greater in the CIS arm than in the with P-VABEC alone arm (OS, 59% vs 40%, P =.016; PFS, 51% vs 38%, P =.053).

When divided according to the IPI risk, the low-risk patients showed no significant differences in OS and PFS over the 5 years with or without CIP (OS, 69% vs 62%, P =.66; PFS, 62% vs 54%, P =.42). However, the high-risk patients showed significant 5-year improvement with the addition of CIP (OS, 49% vs 26%, P =.01; PFS, 40% vs 26%, P =.09).

In the intention-to-treat analysis between the P-VABEC and P-VABEC-CIP arms, respectively, the responses to the therapy showed no significant differences in the complete (58% vs 64%), partial (24% vs 24%), and nonresponders (14% vs 7%), and in the early deaths (4% vs 5%) and treatment-related mortality (6% vs 6%). All cases of treatment-related mortality occurred during the P-VABEC phase of treatment.

There were no significant differences in toxicities between the 2 treatment groups.

Dr. Martelli also indicated that a direct comparison between the 8-week P-VABEC and P-VABEC-CIP treatment and the use of the 24-week CHOP regimen of the GELA study demonstrated very favourable 5-year OS for the use of CIP (40% vs 59% vs 45%, respectively) and PFS (38% vs 51% vs 30%).

On the basis that the combination of rituximab with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) has now become the standard therapy for these patients, Dr. Martelli concluded, "A brief chemotherapy regimen that can be devised for elderly patients would use P-VABEC plus rituximab in the low risk patients and P-VABEC plus rituximab followed by CIP for those with high risk, which should be employed for elderly patients who are not eligible for R-CHOP and needs to be compared with R-CHOP in a prospective study."

[Study title: Cisplatinum, Idarubicin, Prednisone (CIP) After P-VABEC Chemotherapy Improves Survival in Elderly Patients With Diffuse Large-Cell Lymphoma: Long-Term Follow-Up. Abstract 229]