title: 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.
abstract: OBJECTIVE
  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 x 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.
authors.affiliation: Dipartimento di Oncologia ed Ematologia, Università di Modena e Reggio Emilia, Modena, Italy. federico@unimore.it
authors.forename: Massimo
authors.initials: M
authors.lastname: Federico
authors.forename: Stefano
authors.initials: S
authors.lastname: Luminari
authors.forename: Paolo G
authors.initials: PG
authors.lastname: Gobbi
authors.forename: Stefano
authors.initials: S
authors.lastname: Sacchi
authors.forename: Nicola
authors.initials: N
authors.lastname: Di Renzo
authors.forename: Marco
authors.initials: M
authors.lastname: Lombardo
authors.forename: Francesco
authors.initials: F
authors.lastname: Merli
authors.forename: Luca
authors.initials: L
authors.lastname: Baldini
authors.forename: Caterina
authors.initials: C
authors.lastname: Stelitano
authors.forename: Giovanni
authors.initials: G
authors.lastname: Partesotti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Polimeno
authors.forename: Antonella
authors.initials: A
authors.lastname: Montanini
authors.forename: Caterina
authors.initials: C
authors.lastname: Mammi
authors.forename: Maura
authors.initials: M
authors.lastname: Brugiatelli
mesh_terms: D018943:Anthracyclines / Q000008:administration & dosage* / Q000633:toxicity; D015251:Epirubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005965:Glucuronates / Q000008:administration & dosage; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D011379:Prognosis; D012074:Remission Induction; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines; D005965:Glucuronates; C074868:epidoxorubicin glucuronide; D015251:Epirubicin; D015255:Idarubicin