title: A pilot study on the use of the ProMACE-CytaBOM regimen as a first-line treatment of advanced follicular non-Hodgkin's lymphoma. Gruppo Italiano per lo Studio dei Linfomi.
abstract: BACKGROUND
  The role of intensive conventional dose chemotherapy in advanced low grade non-Hodgkin's lymphomas is a matter of debate. The Gruppo Italiano per lo Studio dei Linfomi conducted a study to evaluate the efficacy and toxicity of a third-generation polychemotherapeutic regimen, ProMACE-CytaBOM, as a first-line therapy in a selected group of patients with advanced follicular non-Hodgkin's lymphoma (Fo-NHL) who were younger than 60 years.
  
  
  METHODS
  Thirty-nine patients were included in the study (14 males, 25 females; median age, 44 years; age range, 22-60 years). Their WF histotypes were B (9 patients), C (23 patients), and D (7 patients). All of the patients had disease in an advanced clinical stage (Stage III, 15 patients; Stage IV, 24 patients), and 9 patients had B symptoms. According to the age-adjusted International Prognostic Index (IPI), 20 patients exhibited low-intermediate risk, 14 high-intermediate risk, and 5 high risk. Three of the patients were not considered evaluable because they withdrew their consent after three (one patient) and four (two patients) cycles of therapy (one of these patients was in complete remission [CR], and two were in partial remission [PR]). Of the 36 evaluable patients, 4 received IF-RT after the 6 planned cycles of therapy.
  
  
  RESULTS
  CR was achieved in 20 patients (55.5%) and PR in 14 (38.8%). One patient (2.7%) experienced disease progression during the treatment program. Eight of the 20 patients with CR (40%) relapsed. Eight patients (22.2%) died: 6 died of disease progression, 1 died of therapy consequences, and 1 died of an unrelated cause. With a median follow-up of 49 months (range, 28-79 months), the disease free survival rate was 60%. The overall survival rate was 80% after a median follow-up of 44 months (range, 3-79 months). The IPI stratification of patients showed a borderline statistical difference in terms of time to treatment failure and overall survival. The main hematologic toxicity was neutropenia (Grade 3 in approximately 10% of patients). One patient died of sepsis. Cotrimoxazole prophylaxis was always given. Cardiac toxicity (Grade 3) was observed in 1 patient at the end of the planned therapy. The average relative dose intensity of the drugs was 89% of the projected dose, without the regular use of growth factors.
  
  
  CONCLUSIONS
  This study indicates that ProMACE-CytaBOM could be a suitable regimen for adult patients with advanced Fo-NHL, allowing a good CR rate and very good disease free survival rate. However, the occurrence of severe, albeit limited, adverse effects suggests that this regimen should first be used in controlled therapeutic protocols to verify its efficacy with respect to less intensive approaches.
authors.affiliation: Servizio di Ematologia, Istituto di Scienze Mediche, Università di Milano, Ospedale Maggiore, I.R.C.C.S., Italy.
authors.forename: L
authors.initials: L
authors.lastname: Baldini
authors.forename: A
authors.initials: A
authors.lastname: Guffanti
authors.forename: P
authors.initials: P
authors.lastname: Gobbi
authors.forename: M
authors.initials: M
authors.lastname: Colombi
authors.forename: M
authors.initials: M
authors.lastname: Federico
authors.forename: P
authors.initials: P
authors.lastname: Avanzini
authors.forename: L
authors.initials: L
authors.lastname: Cavanna
authors.forename: C
authors.initials: C
authors.lastname: Pieresca
authors.forename: V
authors.initials: V
authors.lastname: Silingardi
authors.forename: A T
authors.initials: AT
authors.lastname: Maiolo
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001761:Bleomycin / Q000009:adverse effects / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D003561:Cytarabine / Q000009:adverse effects / Q000627:therapeutic use; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D005047:Etoposide / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D010865:Pilot Projects; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D012074:Remission Induction; D016019:Survival Analysis; D017211:Treatment Failure; D014750:Vincristine / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D003561:Cytarabine; D001761:Bleomycin; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone; D008727:Methotrexate