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
Eur J Haematol 2006. © Blackwell Munksgaard 2006. 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.
Document Type: Research Article
Affiliations: 1: Dipartimento di Oncologia ed Ematologia, Università di Modena e Reggio Emilia, Modena, Italy 2: Medicina Interna e Oncologia Medica, Università di Pavia, IRCCS Policlinico San Matteo, Pavia, Italy 3: Unità Operativa di Ematologia ed Oncologia Medica, C.R.O.B., Ospedale Oncologico Regionale, Rionero in Vulture (PZ), Italy 4: Dipartimento di Oncologia, USL di Pescara, Ospedale Santo Spirito, Pescara, Italy 5: Servizio di Ematologia, Azienda Ospedaliera Arcispedale S. Maria Nuova, Reggio Emilia, Italy 6: Unità Malattie Linfoproliferative, Dipartimento di Ematologia, Centro G. Marcora, Ospedale Maggiore, IRCCS, Milano, Italy 7: Divisione di Ematologia, Azienda Ospedaliera ‘Bianchi-Melacrino-Morelli’, Reggio Calabria, Italy 8: Divisione di Medicina, Ospedale Civile, Sassuolo (MO) 9: U.O Semplice di Oncoematologia, Divisione di Medicina, Ospedale ‘F. Miulli’, Acquaviva delle Fonti (BA), Italy 10: Divisione di Ematologia, Azienda Ospedaliera Papardo, Messina, Italy
Publication date: March 1, 2006