title: Randomized Phase II trial of thalidomide alone versus thalidomide plus interferon alpha in patients with refractory multiple myeloma.
abstract: The potential synergistic anti-myeloma effect for thalidomide combining with interferon alpha was not yet clear clinically. From March 2001 to January 2004, a total of 28 heavily pretreated multiple myleoma (MM) patients were enrolled in this open-labeled, randomized Phase II study. Patients with refractory MM were randomized to receive either thalidomide alone (200 mg/day up to the maximum dose 800 mg/day, arm B) or the combination of thalidomide and interferon alpha (3 MIU/m(2) subcutaneous injection 3 times weekly, arm A). The objective of this study was to compare the safety and efficacy of thalidomide alone to combined regimen. The patients' characteristics were similar between the 2 arms. However, the average treatment duration was significantly longer in the arm B than the arm A (236 days versus 101 days, p = 0.029). Serum levels of paraprotein decline >/= 25 percent were obtained in 6 of 12 patients (50.0 percent) treated with arm B and 3 of the 16 patients (18.8 percent) treated with arm A. The estimated time to event was 7.9 months (95 percent confidence interval [95%CI], 0.5-15.4) for arm B and 1.5 months (95%CI, 0.0-3.4) for arm A (log-rank test, p = 0.0193). The major adverse events in both arms consisted of neutropenia, anemia, thrombocytopenia, constipation, somnolence, and skin rash. Our study showed that thalidomide alone was effective and tolerated in patients with relapsed or refractory MM. The thalidomide combined with interferon alpha resulted in a lower frequency of paraprotein response, shorter treatment-duration and 25 percent of patients' refusing rate. It may be concluded that the combined regimen is not well tolerated in our patients and needed to be further evaluated in the future.
authors.affiliation: Section of Medical Oncology, Department of Medicine, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, Taiwan. tjchiou@vghtpe.gov.tw
authors.forename: Tzeon-Jye
authors.initials: TJ
authors.lastname: Chiou
authors.forename: Teng-Hsu
authors.initials: TH
authors.lastname: Wang
authors.forename: Tsu-Yi
authors.initials: TY
authors.lastname: Chao
authors.forename: Sheng-Fung
authors.initials: SF
authors.lastname: Lin
authors.forename: Jih-Luh
authors.initials: JL
authors.lastname: Tang
authors.forename: Tsai-Yun
authors.initials: TY
authors.lastname: Chen
authors.forename: Ming-Chih
authors.initials: MC
authors.lastname: Chang
authors.forename: Erh-Jung
authors.initials: EJ
authors.lastname: Hsueh
authors.forename: Po-Min
authors.initials: PM
authors.lastname: Chen
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D009194:Myeloma Proteins / Q000378:metabolism; D010266:Paraproteins / Q000378:metabolism; D011994:Recombinant Proteins; D013624:Taiwan / Q000453:epidemiology; D013792:Thalidomide / Q000008:administration & dosage; D013997:Time Factors; D017211:Treatment Failure; D016896:Treatment Outcome; D016312:Treatment Refusal
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D009194:Myeloma Proteins; D010266:Paraproteins; D011994:Recombinant Proteins; D013792:Thalidomide