Haematologica 2002; 87:(11)ELT43
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Low-dose epirubicin in combination with cyclophosphamide, vinblastine and prednisone (mini-CEOP) for the treatment of aggressive non-Hodgkin's lymphoma in elderly patients
Dino Veneri, Flavia Zanetti, *Massimo Franchini, Mauro Krampera, Giovanni Pizzolo
*Dipartimento di Medicina Clinica e Sperimentale, Sezione di Ematologia, Università di Verona; *Servizio di Immunoematologia e Trasfusione, Azienda Ospedaliera di Verona, Verona, Italy.
Correspondence: Dr. Dino Veneri, Dipartimento di Medicina Clinica e Sperimentale, Sezione di Ematologia, Università di Verona, 37134 Verona, Italy. E-mail: dino.veneri@univr.it

We report the response to mini-CEOP chemotherapy combination (epirubicin, cyclophosphamide, vinblastine and prednisone) in 44 elderly patients with aggressive non-Hodgkin's lymphoma (NHL) treated in a single institution. Complete remission (CR) was achieved in 21 patients (47.7%) and partial remission in 12 patients (27.3%). We observed one toxic death. The median disease free survival was 22 months (range 6-87 months). Twelve patients (27.2%) are in continuous CR. These data show that mini-CEOP is an effective and safe chemotherapy regimen for elderly patients with aggressive-histology NHL.
High grade non-Hodgkin's lymphomas (NHL) have a peak of incidence in patients (pts) over 60 years. Aggressive full dose chemotherapy regimes are often difficult do deliver in these pts.1,2
In this study we evaluated the feasibility and efficacy of mini-CEOP chemotherapy regimen (low-dose epirubicin associated with cyclophosphamide, vinblastine and prednisone)3 in 44 consecutive untreated elderly pts affected by aggressive non-Hodgkin's lymphoma (median age: 73 years; range: 67-86 years; M/F 20/24). All patients were admitted to our Department between March 1994 and July 2001. Forty cases were large B cell lymphomas and 4 were peripheral T cell lymphomas. According to the Ann Arbor staging system, 22 pts (50%) were in stage II, 3 pts (6.8%) in stage III and 19 pts (43.2%) in stage IV. Four pts (9.1%) had bulky disease at diagnosis and 36 pts (81.8%) had extranodal involvement (7 liver, 7 spleen, 3 gut, 3 stomach, 3 Waldeyer's ring, 3 lung, 1 thyroid, 1 testicle, 2 tongue, 1 breast, 2 pleura, 1 jaw, 1 palate, 1 pancreas). All pts were negative at human immunodeficiency-virus test. According to International Prognostic Factor Index (IPI),4 3 were low-risk (6.8%), 14 low/intermediate risk (31.8%), 12 intermediate/high risk 27.3%) and 15 high risk (34.1%) pts. Mini-CEOP regimen is shown in Table 1. Treatment consisted of 4 cycles in stage II, 6 cycles in stage III and 8 cycles in stage IV and was completed in 27/44 pts (61.3%). Additional involved-field radiotherapy (25-30 Gy) was carried out in 19/44 cases (43.1%), i.e. in 11/19 pts (57,8%) in stage II and in 8/19 pts (42%) with residual mass after chemotherapy. Complete remission (CR) was achieved in 21 pts (47.7%) and partial remission (PR) in 12 pts (27.2%). Nine/21 pts in CR (42.8%) eventually relapsed. Rescue treatments were carried out in most of them. Twelve/21 pts are in continuos CR (CCR) with a median disease free survival of 22 months (range 6-87). In total, 12/44 pts (27.2%) are in CCR. Figure 1 reports the overall and disease free survival curves. A CR was observed in all 3 pts with low IPI, in 10/14 (71.4%) with low-intermediate IPI, in 5/12 (41.7%) with intermediate-high IPI and 3/15 (20%) with high risk IPI. No response was observed in 4 pts (9.1%) and progression during treatment occured in 6 pts (13.6%). During the treatment course we observed symptomatic infections in 4 pts, mild kidney failure in 1 pt, fever of unknown origin in 8 pts. Toxic death occured in 1/44 (2.3%) pts. Ten pts needed blood transfusion support because of moderate anemia and G-CSF was administered in 11 pts due to severe neutropenia (neutrophils < 0.5x109/L).
As reported by many authors1,2,5,6 aggressive non-Hodgkin lymphomas in elderly pts have a more severe clinical presentation and poorer outcome as compared to younger pts. Most of our pts were in advanced stage and had an unfavorable IPI and extranodal involvement at diagnosis. In spite of these poor prognostic indicators and of the advanced median age of our pts (73 years), mini-CEOP proved its efficacy both in terms of CR (47.7%) and of disease free survival (57.1%), with low incidence of toxic effects. These results are as good as those obtained with more intensive regimens5 and might be further improved in association with anti-CD20 monoclonal antibody.6

 

References

  1. Salvagno L, Errante D, Bianco A, Palmisano V, Ballerini F, Boccalon M, et al. S. Treatment of non-Hodgkin lymphoma in the elderly. The Italian studies. Tumori (Suppl) 2002; 88:20-5.
  2. Tirelli U, Bernardi D. Non-Hodgkin's lymphoma in the elderly. Tumori (Suppl) 2002; 88:17-9.
  3. Bertini M, Merli F, Pergo D, Cabras M, Liberati M, Vitolo U, et al.. Evaluation of efficacy, tolerability and QQL of P-VEBEC vs. mini-CEOP, two schedules specifically devised for elderly patients affected by diffuse large cell lymphoma: prelimimary results a randomized trial. Proc. Am. Soc. Clin. Oncol. 19, 38 Meet., 40a, 2000.
  4. A predictive model for aggressive non-Hodgkin's lymphoma. The International Non-Hodgkin's Lymphoma Prognostic Factors Project. N Engl J Med. 1993; 329:987-94.
  5. Zinzani PL, Storti S, Zaccaria A, Moretti L, Magagnoli M, Pavone E, et al. Elderly aggressive-histology non-Hodgkin's lymphoma: first-line VNCOP-B regimen experience on 350 pts. Blood 1999; 94:33-8.
  6. Coiffier B, Haioun C, Ketterer N, Engert A, Tilly H, Ma D, et al. Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma: a multicenter phase II study. Blood. 1998; 92:1927-32.

 

 

 

Table 1. Mini-CEOP regimen

 

Drug Dose Timing

 

Cyclophosphamide 750 mg/m2 iv day 1

Epirubicin 50 mg/m2 iv day 1

Vinblastine 5 mg/m2 iv day 1

Prednisone 60 mg/m2 oral days 1-5

 

Note: cycles every 28 days.