Long-term results of an intensive regimen: VEBEP plus involved-field radiotherapy in advanced Hodgkin's disease

Simonetta Viviani, Valeria Bonfante, Armando Santoro, Marcello Zanini, Liliana Devizzi, Anna Di Russo, Fulvia Soncini, Fabrizio Villani, Guido Ragni, Pinuccia Valagussa, Gianni Bonadonna

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

PURPOSE: This pilot study was conducted to evaluate the efficacy and toxicity of a new intensive drug regimen, combined with involved-nodal-field radiotherapy, in advanced Hodgkin's disease not treated by chemotherapy. PATIENTS AND METHODS: From September 1990 to March 1993, 73 evaluable patients with newly diagnosed stage IIB, III (A and B), and IV (A and B) Hodgkin's disease or who were relapsing after primary subtotal or total nodal irradiation were treated with eight cycles of etoposide, epirubicin, bleomycin, cyclophosphamide, and prednisolone (VEBEP) followed by radiotherapy (30-36 Gy) to the nodal site or sites of pretreatment disease. The median duration of follow-up was 68 months. RESULTS: The complete remission rate was 94% (95% CI: 86-98). At 6 years, freedom from progression and overall survival rates were 78% (95% CI: 68-88) and 82% (95% CI: 73-91), respectively. There was one episode of fatal sepsis after bone marrow aplasia that occurred after VEBEP and extended-field irradiation. Hematologic toxicity during chemotherapy was acceptable; without the support of growth factors, grade IV leukopenia and grade IV neutropenia, as determined within cycles, occurred in 38% and 85% of patients, respectively, but was reversible in the vast majority of patients by the day of treatment recycle. No episodes of epidoxorubicin-related cardiomyopathy or symptomatic pulmonary toxicity were documented. Overt and/or subclinical hypothyroidism occurred in 38% of cases. Gonadal damage was evident in the large majority of male patients but reversible in half of them, whereas permanent sterility was observed in females at least 35 years of age. No secondary leukemia has been so far detected. DISCUSSION: VEBEP followed by involved-nodal-field radiotherapy is an effective treatment for chemotherapy-naive Hodgkin's disease and is associated to acceptable rates of acute and intermediate-term toxicity. This intensive regimen, which does not routinely require the support of hematopoietic growth factors and can be delivered in an outpatient setting, warrants a prospective comparison in a randomized trial versus one of the more effective standard-combination regimens.

Original languageEnglish
Pages (from-to)275-282
Number of pages8
JournalThe cancer journal from Scientific American
Volume5
Issue number5
Publication statusPublished - Sep 1999

Fingerprint

Hodgkin Disease
Radiotherapy
Drug Therapy
Intercellular Signaling Peptides and Proteins
Epirubicin
Bleomycin
Leukopenia
Etoposide
Prednisolone
Hypothyroidism
Neutropenia
Cardiomyopathies
Cyclophosphamide
Infertility
Sepsis
Leukemia
Outpatients
Survival Rate
Bone Marrow
Lung

Keywords

  • Advanced stage
  • Chemotherapy
  • Hodgkin's disease
  • Involved-field radiotherapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Long-term results of an intensive regimen : VEBEP plus involved-field radiotherapy in advanced Hodgkin's disease. / Viviani, Simonetta; Bonfante, Valeria; Santoro, Armando; Zanini, Marcello; Devizzi, Liliana; Di Russo, Anna; Soncini, Fulvia; Villani, Fabrizio; Ragni, Guido; Valagussa, Pinuccia; Bonadonna, Gianni.

In: The cancer journal from Scientific American, Vol. 5, No. 5, 09.1999, p. 275-282.

Research output: Contribution to journalArticle

Viviani, Simonetta ; Bonfante, Valeria ; Santoro, Armando ; Zanini, Marcello ; Devizzi, Liliana ; Di Russo, Anna ; Soncini, Fulvia ; Villani, Fabrizio ; Ragni, Guido ; Valagussa, Pinuccia ; Bonadonna, Gianni. / Long-term results of an intensive regimen : VEBEP plus involved-field radiotherapy in advanced Hodgkin's disease. In: The cancer journal from Scientific American. 1999 ; Vol. 5, No. 5. pp. 275-282.
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abstract = "PURPOSE: This pilot study was conducted to evaluate the efficacy and toxicity of a new intensive drug regimen, combined with involved-nodal-field radiotherapy, in advanced Hodgkin's disease not treated by chemotherapy. PATIENTS AND METHODS: From September 1990 to March 1993, 73 evaluable patients with newly diagnosed stage IIB, III (A and B), and IV (A and B) Hodgkin's disease or who were relapsing after primary subtotal or total nodal irradiation were treated with eight cycles of etoposide, epirubicin, bleomycin, cyclophosphamide, and prednisolone (VEBEP) followed by radiotherapy (30-36 Gy) to the nodal site or sites of pretreatment disease. The median duration of follow-up was 68 months. RESULTS: The complete remission rate was 94{\%} (95{\%} CI: 86-98). At 6 years, freedom from progression and overall survival rates were 78{\%} (95{\%} CI: 68-88) and 82{\%} (95{\%} CI: 73-91), respectively. There was one episode of fatal sepsis after bone marrow aplasia that occurred after VEBEP and extended-field irradiation. Hematologic toxicity during chemotherapy was acceptable; without the support of growth factors, grade IV leukopenia and grade IV neutropenia, as determined within cycles, occurred in 38{\%} and 85{\%} of patients, respectively, but was reversible in the vast majority of patients by the day of treatment recycle. No episodes of epidoxorubicin-related cardiomyopathy or symptomatic pulmonary toxicity were documented. Overt and/or subclinical hypothyroidism occurred in 38{\%} of cases. Gonadal damage was evident in the large majority of male patients but reversible in half of them, whereas permanent sterility was observed in females at least 35 years of age. No secondary leukemia has been so far detected. DISCUSSION: VEBEP followed by involved-nodal-field radiotherapy is an effective treatment for chemotherapy-naive Hodgkin's disease and is associated to acceptable rates of acute and intermediate-term toxicity. This intensive regimen, which does not routinely require the support of hematopoietic growth factors and can be delivered in an outpatient setting, warrants a prospective comparison in a randomized trial versus one of the more effective standard-combination regimens.",
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AU - Zanini, Marcello

AU - Devizzi, Liliana

AU - Di Russo, Anna

AU - Soncini, Fulvia

AU - Villani, Fabrizio

AU - Ragni, Guido

AU - Valagussa, Pinuccia

AU - Bonadonna, Gianni

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N2 - PURPOSE: This pilot study was conducted to evaluate the efficacy and toxicity of a new intensive drug regimen, combined with involved-nodal-field radiotherapy, in advanced Hodgkin's disease not treated by chemotherapy. PATIENTS AND METHODS: From September 1990 to March 1993, 73 evaluable patients with newly diagnosed stage IIB, III (A and B), and IV (A and B) Hodgkin's disease or who were relapsing after primary subtotal or total nodal irradiation were treated with eight cycles of etoposide, epirubicin, bleomycin, cyclophosphamide, and prednisolone (VEBEP) followed by radiotherapy (30-36 Gy) to the nodal site or sites of pretreatment disease. The median duration of follow-up was 68 months. RESULTS: The complete remission rate was 94% (95% CI: 86-98). At 6 years, freedom from progression and overall survival rates were 78% (95% CI: 68-88) and 82% (95% CI: 73-91), respectively. There was one episode of fatal sepsis after bone marrow aplasia that occurred after VEBEP and extended-field irradiation. Hematologic toxicity during chemotherapy was acceptable; without the support of growth factors, grade IV leukopenia and grade IV neutropenia, as determined within cycles, occurred in 38% and 85% of patients, respectively, but was reversible in the vast majority of patients by the day of treatment recycle. No episodes of epidoxorubicin-related cardiomyopathy or symptomatic pulmonary toxicity were documented. Overt and/or subclinical hypothyroidism occurred in 38% of cases. Gonadal damage was evident in the large majority of male patients but reversible in half of them, whereas permanent sterility was observed in females at least 35 years of age. No secondary leukemia has been so far detected. DISCUSSION: VEBEP followed by involved-nodal-field radiotherapy is an effective treatment for chemotherapy-naive Hodgkin's disease and is associated to acceptable rates of acute and intermediate-term toxicity. This intensive regimen, which does not routinely require the support of hematopoietic growth factors and can be delivered in an outpatient setting, warrants a prospective comparison in a randomized trial versus one of the more effective standard-combination regimens.

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