The length of treatment of aggressive non-Hodgkin's lymphomas established according to the international prognostic index score

Long-term results of the GISL LA03 study

Massimo Federico, Stefano Luminari, Paolo G. Gobbi, Stefano Sacchi, Nicola Di Renzo, Marco Lombardo, Francesco Merli, Luca Baldini, Caterina Stelitano, Giovanni Partesotti, Giuseppe Polimeno, Antonella Montanini, Caterina Mammi, Maura Brugiatelli

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Objectives: To compare two different schedules of two different anthracycline-containing regimens, where length of treatment is modulated according to the international prognostic index (IPI) in patients with aggressive non-Hodgkin's Lymphoma (NHL). Methods: In 1993 the Gruppo Italiano per lo Studio dei Linfomi (GISL) started a randomized 2 × 2 factorial phase III clinical trial for patients with newly diagnosed aggressive NHL comparing ProME(Epidoxorubicin)CE-CytaBOM (PE-C) to ProMI(Idarubicin)CE-CytaBOM (PI-C) and a fixed to a flexible treatment schedule where anthracycline dose was to be modulated according to observed hematological toxicity. Patients with low or low-intermediate IPI (IPI 0-2) and those with intermediate-high or high IPI (IPI 3-5) should receive six or eight courses, respectively. Involved-field radiotherapy was allowed for patients with initial bulky disease or with residual masses. Results: Three hundred and fifty-six patients were registered into the study and randomized. Patients were well balanced among the four study arms in terms of clinical characteristics and prognostic factors. Three hundred and forty-five patients were available for evaluation of study endpoints. At the end of induction therapy complete remission rate was 61%, 5-year failure-free survival (FFS) rate was 40% and 5-year overall survival (OS) rate was 59%; no differences were observed according to treatment arms. Patients in the flexible arm received higher dose intensity of anthracycline (P <0.001) with no apparent increase in toxicity. However, the flexible schedule was not superior to the fixed one. Patients with IPI 3-5 showed lower response rates (45% vs. 67%: P <0.0001) and lower 5-year FFS (29% vs. 45%: P <0.0001) compared to those with IPI 0-2. Conclusions: six courses of fixed or flexible PE-C or PI-C can determine a promising success rate in patients with advanced aggressive NHL with IPI 0-2, whereas the same regimens are less effective in patients with IPI 3-5, even if two additional courses are delivered. For the latter group of patients innovative approaches are warranted.

Original languageEnglish
Pages (from-to)217-229
Number of pages13
JournalEuropean Journal of Haematology
Volume76
Issue number3
DOIs
Publication statusPublished - Mar 2006

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Non-Hodgkin's Lymphoma
Anthracyclines
Therapeutics
Idarubicin
Appointments and Schedules
Survival Rate
Phase III Clinical Trials
Radiotherapy
Survival

Keywords

  • Aggressive NHL
  • Epidoxorubicin
  • Idarubicin
  • IPI
  • ProMACE-CytaBOM

ASJC Scopus subject areas

  • Hematology

Cite this

The length of treatment of aggressive non-Hodgkin's lymphomas established according to the international prognostic index score : Long-term results of the GISL LA03 study. / Federico, Massimo; Luminari, Stefano; Gobbi, Paolo G.; Sacchi, Stefano; Di Renzo, Nicola; Lombardo, Marco; Merli, Francesco; Baldini, Luca; Stelitano, Caterina; Partesotti, Giovanni; Polimeno, Giuseppe; Montanini, Antonella; Mammi, Caterina; Brugiatelli, Maura.

In: European Journal of Haematology, Vol. 76, No. 3, 03.2006, p. 217-229.

Research output: Contribution to journalArticle

Federico, Massimo ; Luminari, Stefano ; Gobbi, Paolo G. ; Sacchi, Stefano ; Di Renzo, Nicola ; Lombardo, Marco ; Merli, Francesco ; Baldini, Luca ; Stelitano, Caterina ; Partesotti, Giovanni ; Polimeno, Giuseppe ; Montanini, Antonella ; Mammi, Caterina ; Brugiatelli, Maura. / The length of treatment of aggressive non-Hodgkin's lymphomas established according to the international prognostic index score : Long-term results of the GISL LA03 study. In: European Journal of Haematology. 2006 ; Vol. 76, No. 3. pp. 217-229.
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abstract = "Objectives: To compare two different schedules of two different anthracycline-containing regimens, where length of treatment is modulated according to the international prognostic index (IPI) in patients with aggressive non-Hodgkin's Lymphoma (NHL). Methods: In 1993 the Gruppo Italiano per lo Studio dei Linfomi (GISL) started a randomized 2 × 2 factorial phase III clinical trial for patients with newly diagnosed aggressive NHL comparing ProME(Epidoxorubicin)CE-CytaBOM (PE-C) to ProMI(Idarubicin)CE-CytaBOM (PI-C) and a fixed to a flexible treatment schedule where anthracycline dose was to be modulated according to observed hematological toxicity. Patients with low or low-intermediate IPI (IPI 0-2) and those with intermediate-high or high IPI (IPI 3-5) should receive six or eight courses, respectively. Involved-field radiotherapy was allowed for patients with initial bulky disease or with residual masses. Results: Three hundred and fifty-six patients were registered into the study and randomized. Patients were well balanced among the four study arms in terms of clinical characteristics and prognostic factors. Three hundred and forty-five patients were available for evaluation of study endpoints. At the end of induction therapy complete remission rate was 61{\%}, 5-year failure-free survival (FFS) rate was 40{\%} and 5-year overall survival (OS) rate was 59{\%}; no differences were observed according to treatment arms. Patients in the flexible arm received higher dose intensity of anthracycline (P <0.001) with no apparent increase in toxicity. However, the flexible schedule was not superior to the fixed one. Patients with IPI 3-5 showed lower response rates (45{\%} vs. 67{\%}: P <0.0001) and lower 5-year FFS (29{\%} vs. 45{\%}: P <0.0001) compared to those with IPI 0-2. Conclusions: six courses of fixed or flexible PE-C or PI-C can determine a promising success rate in patients with advanced aggressive NHL with IPI 0-2, whereas the same regimens are less effective in patients with IPI 3-5, even if two additional courses are delivered. For the latter group of patients innovative approaches are warranted.",
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T2 - Long-term results of the GISL LA03 study

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AU - Gobbi, Paolo G.

AU - Sacchi, Stefano

AU - Di Renzo, Nicola

AU - Lombardo, Marco

AU - Merli, Francesco

AU - Baldini, Luca

AU - Stelitano, Caterina

AU - Partesotti, Giovanni

AU - Polimeno, Giuseppe

AU - Montanini, Antonella

AU - Mammi, Caterina

AU - Brugiatelli, Maura

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N2 - Objectives: To compare two different schedules of two different anthracycline-containing regimens, where length of treatment is modulated according to the international prognostic index (IPI) in patients with aggressive non-Hodgkin's Lymphoma (NHL). Methods: In 1993 the Gruppo Italiano per lo Studio dei Linfomi (GISL) started a randomized 2 × 2 factorial phase III clinical trial for patients with newly diagnosed aggressive NHL comparing ProME(Epidoxorubicin)CE-CytaBOM (PE-C) to ProMI(Idarubicin)CE-CytaBOM (PI-C) and a fixed to a flexible treatment schedule where anthracycline dose was to be modulated according to observed hematological toxicity. Patients with low or low-intermediate IPI (IPI 0-2) and those with intermediate-high or high IPI (IPI 3-5) should receive six or eight courses, respectively. Involved-field radiotherapy was allowed for patients with initial bulky disease or with residual masses. Results: Three hundred and fifty-six patients were registered into the study and randomized. Patients were well balanced among the four study arms in terms of clinical characteristics and prognostic factors. Three hundred and forty-five patients were available for evaluation of study endpoints. At the end of induction therapy complete remission rate was 61%, 5-year failure-free survival (FFS) rate was 40% and 5-year overall survival (OS) rate was 59%; no differences were observed according to treatment arms. Patients in the flexible arm received higher dose intensity of anthracycline (P <0.001) with no apparent increase in toxicity. However, the flexible schedule was not superior to the fixed one. Patients with IPI 3-5 showed lower response rates (45% vs. 67%: P <0.0001) and lower 5-year FFS (29% vs. 45%: P <0.0001) compared to those with IPI 0-2. Conclusions: six courses of fixed or flexible PE-C or PI-C can determine a promising success rate in patients with advanced aggressive NHL with IPI 0-2, whereas the same regimens are less effective in patients with IPI 3-5, even if two additional courses are delivered. For the latter group of patients innovative approaches are warranted.

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