title: Phase II fludarabine and cyclophosphamide for the treatment of indolent B cell non-follicular lymphomas: final results of the LL02 trial of the Gruppo Italiano per lo Studio dei Linfomi (GISL).
abstract: Indolent non-follicular non-Hodgkin lymphomas (INFL) are a heterogeneous subset whose treatment has been poorly investigated. In this context we have evaluated the efficacy and safety of combined fludarabine and cyclophosphamide (FC) upfront therapy. Sixty-three patients with advanced INFL were enrolled in the study. Therapy consisted in FC combination (25 and 250 mg/m(2), i.v., respectively, for three consecutive days) every 28 days for six courses. After histological review, 61 patients (36 men, median age 64 years, range 40-70 years) were evaluated (22 small lymphocytic, 11 lymphoplasmacytic, 25 marginal zone and 3 CD5-negative non-Hodgkin lymphomas not otherwise specified). Further two patients were excluded for lack of essential data; six patients were withdrawn before the third cycle because of WHO grade III and IV toxicity. At the final evaluation, the overall response rate was 83% with 40.7% of complete remission. Intention-to-treat analysis showed that at the median follow-up of 36 months, overall survival, progression-free survival and failure-free survival were respectively 78%, 60% and 46%; remission duration among the 49 patients achieving complete remission/partial remission at the end of treatment was 65% (44-78) without significant differences between the main histotypes. The most frequent grade III and IV toxic events were haematological (neutropaenia 34%, anaemia 18% and thrombocytopaenia 11%) and infectious (10%). FC is effective for advanced untreated INFL. Early deaths and haematological toxicity suggest careful patient selection and monitoring.
authors.affiliation: Unità Operativa Ematologia 1, Fondazione IRCCS, Cà Granda, Ospedale Maggiore Policlinico, Dipartimento Scienze Mediche, Università degli Studi, Via F. Sforza 35, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ferrario
authors.forename: Francesco
authors.initials: F
authors.lastname: Merli
authors.forename: Stefano
authors.initials: S
authors.lastname: Luminari
authors.forename: Caterina
authors.initials: C
authors.lastname: Stelitano
authors.forename: Donato
authors.initials: D
authors.lastname: Mannina
authors.forename: Mario
authors.initials: M
authors.lastname: Russo
authors.forename: Patrizio
authors.initials: P
authors.lastname: Mazza
authors.forename: Luigi
authors.initials: L
authors.lastname: Marcheselli
authors.forename: Maria Cecilia
authors.initials: MC
authors.lastname: Goldaniga
authors.forename: Massimo
authors.initials: M
authors.lastname: Federico
authors.forename: Luca
authors.initials: L
authors.lastname: Baldini
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007558:Italy; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D012074:Remission Induction; D013921:Thrombocytopenia / Q000139:chemically induced; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine