title: The role of dose size in a chemotherapy regimen (ProMECE-CytaBOM) for the first-line treatment of large B-cell lymphomas: a randomized trial by the Gruppo Italiano Studio Linfomi (GISL).
abstract: BACKGROUND
  It is still unclear the actual contribute of dose intensity (DI), dose size (DS) and dose density (DD) in the conventional chemotherapy of large, B-cell non-Hodgkin lymphomas.
  
  
  METHODS
  A prospective, randomized trial compared the cyclic schedule of ProMECE-CytaBOM chemotherapy (cyc-PC, 6 cycles) with a modified version of it, which administered the same drugs sequentially (seq-PC), with the same planned cumulative DI and an 83% DD, within the same time frame (113 days), but with three times higher DS of all the drugs except vincristine.
  
  
  RESULTS
  Fifty-six patients received cyc-PC and 52 seq-PC. The actual mean cumulative DI was 0.79 +/- 0.15 with cyc-PC, 0.78 +/- 0.17 with seq-PC. Response was complete in 59% and 52%, partial in 20% and 21%, null in 5% and 6%, respectively. There were four toxic deaths (two per arm). Relapses occurred in 36% and 37%, respectively. Toxicity was similar in both arms. Overall, failure-free, progression-free and disease-free survival (median follow-up: 54 months) were statistically indifferent.
  
  
  CONCLUSIONS
  The very similar DI actually delivered in both arm seems to be the main common determinant of the indifferent results recorded. Increasing DS--at least within the limits clinically attainable without stem cell rescue--does not improve results.
authors.affiliation: Medicina Interna, Oncologia e Gastroenterologia, Università di Pavia, IRCCS Policlinico S. Matteo, Pavia, Italy. gobbipg@smatteo.pv.it
authors.forename: P G
authors.initials: PG
authors.lastname: Gobbi
authors.forename: C
authors.initials: C
authors.lastname: Broglia
authors.forename: F
authors.initials: F
authors.lastname: Valentino
authors.forename: C
authors.initials: C
authors.lastname: Mammi
authors.forename: M
authors.initials: M
authors.lastname: Lombardo
authors.forename: F
authors.initials: F
authors.lastname: Merli
authors.forename: S
authors.initials: S
authors.lastname: Luminari
authors.forename: G
authors.initials: G
authors.lastname: Polimeno
authors.forename: A
authors.initials: A
authors.lastname: Riezzo
authors.forename: P
authors.initials: P
authors.lastname: Lambelet
authors.forename: A
authors.initials: A
authors.lastname: Rovati
authors.forename: G R
authors.initials: GR
authors.lastname: Corazza
authors.forename: M
authors.initials: M
authors.lastname: Federico
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D015251:Epirubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D003561:Cytarabine; D001761:Bleomycin; D015251:Epirubicin; D014750:Vincristine; D005047:Etoposide; D003520:Cyclophosphamide; D011241:Prednisone; D008727:Methotrexate