title: Chlorambucil in combination with induction and maintenance rituximab is feasible and active in indolent non-Hodgkin's lymphoma.
abstract: We investigated the toxicity and efficacy of the chimaeric anti-CD20 antibody rituximab in combination with standard-dose chlorambucil in newly diagnosed and relapsed/refractory indolent B-cell lymphoma patients. A total of 29 patients (15 newly diagnosed and 14 relapsed/refractory) with low-grade or follicular B-cell non-Hodgkin's lymphoma (NHL) were included in this phase II study. Therapy consisted of chlorambucil 6 mg/m2/d for 6 consecutive weeks in combination with a standard 4-weekly rituximab administration schedule in the induction phase. Patients responding to the induction therapy received four additional cycles with chlorambucil (6 mg/m2/d for 2 weeks/month) plus rituximab (once a month). Twenty-six patients (89%) completed the treatment; only one patient discontinued treatment because of haematological toxicity. At the end of the study, the dose of chlorambucil had to be reduced in seven patients (27%) and six patients (23%) required a delay in further treatment, as a result of toxicity during consolidation therapy. Only one patient was withdrawn from the study because of progressive disease; the 27 patients evaluable for response at the end of consolidation achieved a clinical response (63% complete response and 26% partial response). A significant CD4+ and CD56+ depletion was observed after induction and during consolidation therapy; two herpes zoster virus infections and one perianal abscess represented major infectious morbidities registered during the study. Based on our preliminary data, the combination of chlorambucil with rituximab seemed to be well tolerated and active. Its definitive role in the treatment of low-grade NHL should be further evaluated in randomized trials.
authors.affiliation: European Institute of Oncology, Milan, Italy. giovanni.martinelli@ieo.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.forename: Daniele
authors.initials: D
authors.lastname: Laszlo
authors.forename: Francesco
authors.initials: F
authors.lastname: Bertolini
authors.forename: Rocco
authors.initials: R
authors.lastname: Pastano
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mancuso
authors.forename: Angelica
authors.initials: A
authors.lastname: Calleri
authors.forename: Anna
authors.initials: A
authors.lastname: Vanazzi
authors.forename: Paola
authors.initials: P
authors.lastname: Santoro
authors.forename: Franco
authors.initials: F
authors.lastname: Cavalli
authors.forename: Emanuele
authors.initials: E
authors.lastname: Zucca
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D002699:Chlorambucil / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D018655:Lymphocyte Count; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000276:immunology; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D002699:Chlorambucil; D000069283:Rituximab