title: Clinical efficacy of immunochemotherapy with fludarabine, epirubicin and rituximab in the treatment for chronic lymphocytic leukaemia and prolymphocytic leukaemia.
abstract: Despite some considerable progress in the therapy for chronic lymphocytic leukaemia (CLL) owing to fludarabine-based regimens and rituximab, no curative treatment is available so far. We conducted an explorative phase II study in patients with CLL, prolymphocytic leukaemia (PLL) and leukaemic lymphoplasmacytic lymphoma (LL) with the combination of fludarabine, epirubicin and rituximab (FER) to improve the complete remission (CR) rate and progression-free survival (PFS). Fludarabine 25 mg/m(2) was administered i.v. on days 1-5 and epirubicin 25 mg/m(2) i.v. on days 4 and 5, and rituximab was added at a dose of 375 mg/m(2) i.v. day 1 in the first cycle and at a dose of 500 mg/m(2) in all consecutive cycles. Patients exhibiting responsive disease after FER were eligible to receive maintenance therapy of up to 12 cycles of rituximab 375 mg/m(2) bimonthly. Forty-four patients (38 CLL, 4 PLL and 2 LL) with a median age of 65 yrs (43-84 yrs) were evaluable. Seventeen patients with CLL had stage Binet C, 14 Binet B and seven symptomatic or rapid progressive stage Binet A. Cytogenetic features showed normal karyotype in nine cases, an isolated deletion (del) 13q in 12 patients, trisomy 12 in 7, del 11 in two and del 17p in 4. Half of the patients (48%) had mutated IgVH genes. Treatment with FER achieved an overall response rate of 95%, including 63% CRs and 32% PRs. Haematological toxicity was considerable. After a median follow-up period of 34 months (range: 8-84 months), median PFS was 61 months and overall survival was yet not reached. All patients with PLL and LL achieved CR. The data support the high efficacy of the combination of rituximab with chemotherapy (FE) and are suggestive of possible benefit with rituximab maintenance therapy for PFS and DFS.
authors.affiliation: Hematology and Oncology, Frankfurt Medical Clinic II, Johann-Wolfgang-Goethe University Hospital, Theodor-Stern-Kai 7, Frankfurt, Germany.
authors.forename: Kai Uwe
authors.initials: KU
authors.lastname: Chow
authors.forename: Soo-Zin
authors.initials: SZ
authors.lastname: Kim
authors.forename: Nils
authors.initials: N
authors.lastname: von Neuhoff
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schlegelberger
authors.forename: Stephan
authors.initials: S
authors.lastname: Stilgenbauer
authors.forename: Lydia
authors.initials: L
authors.lastname: Wunderle
authors.forename: Hans-Joerg
authors.initials: HJ
authors.lastname: Cordes
authors.forename: Lothar
authors.initials: L
authors.lastname: Bergmann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007167:Immunotherapy; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000235:genetics / Q000628:therapy*; D015463:Leukemia, Prolymphocytic / Q000188:drug therapy / Q000235:genetics / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000069283:Rituximab; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D015251:Epirubicin; D000069283:Rituximab; D014740:Vidarabine; C024352:fludarabine