title: A variant of ProMACE-CytaBOM chemotherapy for non-Hodgkin's lymphoma with threefold higher drug dose size but identical cumulative dose intensity. A pilot study of the Italian lymphoma study group (GISL).
abstract: OBJECTIVE
  The positive results of high-dose chemotherapy followed by rescue with bone marrow progenitor cell transplantation are generally ascribed to the high dose size (DS) of the drugs given. However, a concomitant marked increase in dose intensity (DI) is always involved. With the aim of comparing the role of DS and DI in non-Hodgkin's lymphomas, a variant of Fisher's ProMACE-CytaBOM regimen was designed in which the projected cumulative drug DIs remained the same as in the original schedule but the DSs were tripled.
  
  
  METHODS
  Dosages in mg/m(2), route and days of administration were the following: cyclophosphamide 1,950 i.v. on days 1, 64; methotrexate 360 i.v. days 15, 78; vincristine 1.4 iv days 15, 78, 43, 106; etoposide 360 i.v. days 29, 92; epirubicin 120 i.v. days 29, 92; bleomycin 15 i.v. days 43, 106; cytarabine 900 i.v. days 50, 113. Thirty-six outpatients with intermediate- and high-grade non-Hodgkin's lymphomas entered the pilot study; 29 were untreated and 7 had relapse disease. Clinical stage was I in 1 patient, II in 7, III in 5 and IV in 23; 10 had B symptoms; the IPI score was 0-2 in 29 cases and > or =3 in the remaining 7.
  
  
  RESULTS
  Of the 29 previously untreated patients, 16 achieved complete remission, 8 partial remission, 4 developed progressive disease and 1 was withdrawn early from the study because of acute viral hepatitis; subsequently 4 relapsed and 3 died (2 of disease progression, 1 of causes unrelated to the disease). In the pre-treated group 3 patients obtained complete remission, 2 partial remission and in 1 patient the disease progressed; 3 of these pre-treated patients died (1 of progressive disease, 1 of a new relapse, 1 of myocardial infarction during therapy). With a 20-month median follow-up, the 30-month overall and relapse-free survival were 0.58 and 0.70, respectively. G-CSF was administered to all but 2 patients, with median delivery throughout the whole regimen of 8, 400 microg per patient. Actual cumulative DI was 0.82+/-0.11. Grade 3-4 hematologic toxicity consisted of anemia in 3 cases, of leukopenia in 8 and of thrombocytopenia in 2; the same grade of non-hematologic toxicity involved the liver in 2 cases, the heart in 1 (the above mentioned death), the digestive mucosa in 2 and the peripheral nerves in 1 patient.
  
  
  CONCLUSIONS
  The iso-DI sequential variant of the ProMACE-CytaBOM regimen can be considered feasibile, relatively non-toxic, and can be given on an out-patient basis. Limited use of G-CSF is required (about 3 vials after each drug administration). Thus, a randomized trial with the original ProMACE-CytaBOM regimen can be designed.
authors.affiliation: Medicina Interna e Oncologia Medica, Università di Pavia, Policlinico S. Matteo, P.le Golgi 2, 27100 Pavia, Italy. gobbipg@smatteo.pv.it
authors.forename: P G
authors.initials: PG
authors.lastname: Gobbi
authors.forename: M L
authors.initials: ML
authors.lastname: Ghirardelli
authors.forename: P
authors.initials: P
authors.lastname: Avanzini
authors.forename: L
authors.initials: L
authors.lastname: Baldini
authors.forename: G
authors.initials: G
authors.lastname: Quarta
authors.forename: C
authors.initials: C
authors.lastname: Stelitano
authors.forename: C
authors.initials: C
authors.lastname: Broglia
authors.forename: C
authors.initials: C
authors.lastname: Loni
authors.forename: V
authors.initials: V
authors.lastname: Silingardi
authors.forename: E
authors.initials: E
authors.lastname: Ascari
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D001761:Bleomycin / Q000008:administration & dosage / Q000633:toxicity; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000633:toxicity; D003561:Cytarabine / Q000008:administration & dosage / Q000633:toxicity; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000633:toxicity; D005047:Etoposide / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D006801:Humans; D007558:Italy; D008228:Lymphoma, Non-Hodgkin / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000633:toxicity; D008875:Middle Aged; D010865:Pilot Projects; D011241:Prednisone / Q000008:administration & dosage / Q000633:toxicity; D012008:Recurrence; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage / Q000633:toxicity
chemical_list: D003561:Cytarabine; D001761:Bleomycin; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone; D008727:Methotrexate