title: Multicenter, randomized comparative trial of fludarabine and the combination of cyclophosphamide-doxorubicin-prednisone in 92 patients with Waldenström macroglobulinemia in first relapse or with primary refractory disease.
abstract: Few reports are available on the treatment of patients with Waldenström macroglobulinemia (WM) and primary or secondary resistance to alkylating-agent-based regimens. From December 1993 through December 1997, 92 patients with WM resistant to first-line therapy (42) or with first relapse (50) after alkylating-agent therapy were randomly assigned to receive fludarabine (25 mg/m(2) of body-surface area on days 1-5) or cyclophosphamide, doxorubicin (Adriamycin), and prednisone (CAP; 750 mg/m(2) cyclophosphamide and 25 mg/m(2) doxorubicin on day 1 and 40 mg/m(2) prednisone on days 1-5). The first end point evaluated was the response rate after 6 treatment courses. Forty-five patients received CAP and 45 received fludarabine. Two patients died before the first course of chemotherapy. No statistical differences were observed between the 2 treatment arms with respect to hematologic toxicity or infections. Mucositis and alopecia occurred significantly more often in patients treated with CAP. Partial responses were obtained in 14 patients (30%) treated with fludarabine and 5 patients (11%) treated with CAP (P =.019). Responses were more durable in patients treated with fludarabine (19 months versus 3 months), and the event-free survival rate was significantly higher in this group (P <.01). Forty-four patients died, 22 in the fludarabine group and 22 in the CAP group. There was no statistical difference in the median overall survival time in the 2 study arms. Fludarabine was thus more active than CAP in salvage therapy of WM and should be tested as first-line therapy in a randomized comparison with alkylating agents.
authors.affiliation: Département d'hématologie, Hôpital Pitié-Salpétrière, AP-HP, Paris, France. veronique.leblond@psl.ap-hop-paris.fr
authors.forename: V
authors.initials: V
authors.lastname: Leblond
authors.forename: V
authors.initials: V
authors.lastname: Lévy
authors.forename: F
authors.initials: F
authors.lastname: Maloisel
authors.forename: B
authors.initials: B
authors.lastname: Cazin
authors.forename: J P
authors.initials: JP
authors.lastname: Fermand
authors.forename: J L
authors.initials: JL
authors.lastname: Harousseau
authors.forename: L
authors.initials: L
authors.lastname: Remenieras
authors.forename: R
authors.initials: R
authors.lastname: Porcher
authors.forename: M
authors.initials: M
authors.lastname: Gardembas
authors.forename: G
authors.initials: G
authors.lastname: Marit
authors.forename: E
authors.initials: E
authors.lastname: Deconinck
authors.forename: B
authors.initials: B
authors.lastname: Desablens
authors.forename: F
authors.initials: F
authors.lastname: Guilhot
authors.forename: G
authors.initials: G
authors.lastname: Philippe
authors.forename: A
authors.initials: A
authors.lastname: Stamatoullas
authors.forename: O
authors.initials: O
authors.lastname: Guibon
mesh_terms: D000328:Adult; D000368:Aged; D000505:Alopecia / Q000139:chemically induced; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000633:toxicity; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000633:toxicity; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa; D011241:Prednisone / Q000008:administration & dosage; D012008:Recurrence; D016879:Salvage Therapy; D013280:Stomatitis / Q000139:chemically induced; D016019:Survival Analysis; D013810:Therapeutic Equivalency; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000633:toxicity; D008258:Waldenstrom Macroglobulinemia / Q000150:complications / Q000188:drug therapy* / Q000401:mortality
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004317:Doxorubicin; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine; D011241:Prednisone