title: A randomized trial comparing intensified CNOP vs. CHOP in patients with aggressive non-Hodgkin's lymphoma.
abstract: The standard CHOP regimen may cure 30-40% of patients with advanced aggressive non-Hodgkin's lymphoma (ANHL). Mitoxantrone is an anthracenedione, which is active in NHL and its toxicity profile may be more favorable than doxorubicin with respect to alopecia, mucositis and cardiotoxicity. This study was designed to compare the effectiveness of an escalated dose of mitoxantrone with that of standard doxorubicin, used in the CHOP regimen in patients with ANHL. One hundred and forty three eligible patients with ANHL were randomized to receive 6 cycles of either CHOP (n = 71) or intensified CNOP (iCNOP) (n = 72), with mitoxantrone 20 mg/m2, i.v., d.1 instead of doxorubicin. Complete responders (CR) were again randomized either to receive interferon-alpha (IFN-alpha) maintenance (3 MU t.i.w., s.c.) or not. The CR rate was 70 vs. 76% for iCNOP and CHOP (p = 0.45), and the overall response rate was 81 vs. 83%, respectively (p = 0.71). The 5-year failure free survival (FFS) was 48 and 50% in the iCNOP and CHOP arm, respectively (p = 0.45), and the 5-year overall survival (OS) was 61 vs. 64% (p = 0.56). IFN-alpha did not prolong relapse free survival (p = 0.91). iCNOP produced less alopecia (p = 0.001) but more febrile episodes (p = 0.04) than CHOP, while requiring more frequent G-CSF support (p = 0.01). Two cases of acute myelogenous leukemia (AML) were recorded, both in the iCNOP arm (p = 0.14). In conclusion, iCNOP was equally effective to CHOP in patients with ANHL, producing more leukopenia and febrile episodes, but less alopecia. The development of two cases of secondary AML in th e iCNOP arm is of concern.
authors.affiliation: Hematology Section, First Department of Internal Medicine, National and Kapodistrian University of Athens, School of Medicine, Laikon General Hospital, 16 Sevastoupoleos Str., P.O. Box 14044, Athens 11510, Greece. pangalis@otenet.gr
authors.forename: Gerassimos A
authors.initials: GA
authors.lastname: Pangalis
authors.forename: Theodoros P
authors.initials: TP
authors.lastname: Vassilakopoulos
authors.forename: Evridiki
authors.initials: E
authors.lastname: Michalis
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Roussou
authors.forename: Effimia
authors.initials: E
authors.lastname: Vrakidou
authors.forename: Panayiotis
authors.initials: P
authors.lastname: Repousis
authors.forename: Maria K
authors.initials: MK
authors.lastname: Angelopoulou
authors.forename: Marina P
authors.initials: MP
authors.lastname: Siakantaris
authors.forename: John
authors.initials: J
authors.lastname: Korantzis
authors.forename: Argyrios
authors.initials: A
authors.lastname: Symeonidis
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Grigorakis
authors.forename: Ekaterini
authors.initials: E
authors.lastname: Stefanoudakis
authors.forename: Marina
authors.initials: M
authors.lastname: Stamatellou
authors.forename: Konstantinos L
authors.initials: KL
authors.lastname: Bourantas
authors.forename: Themis
authors.initials: T
authors.lastname: Kalmantis
authors.forename: George
authors.initials: G
authors.lastname: Christopoulos
authors.forename: Garyfallia
authors.initials: G
authors.lastname: Kokkinis
authors.forename: Ilias
authors.initials: I
authors.lastname: Mihalakeas
authors.forename: Antonios
authors.initials: A
authors.lastname: Papayiannis
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000627:therapeutic use*; D011239:Prednisolone / Q000627:therapeutic use*; D011241:Prednisone / Q000627:therapeutic use*; D011379:Prognosis; D013997:Time Factors; D016896:Treatment Outcome; D014750:Vincristine / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D016898:Interferon-alpha; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011239:Prednisolone; D008942:Mitoxantrone; D011241:Prednisone