Randomized Phase II trial of thalidomide alone versus thalidomide plus interferon alpha in patients with refractory multiple myeloma.
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.
Chiou
Tzeon-Jye
TJ
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
Wang
Teng-Hsu
TH
Chao
Tsu-Yi
TY
Lin
Sheng-Fung
SF
Tang
Jih-Luh
JL
Chen
Tsai-Yun
TY
Chang
Ming-Chih
MC
Hsueh
Erh-Jung
EJ
Chen
Po-Min
PM
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
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D009194:Myeloma Proteins; D010266:Paraproteins; D011994:Recombinant Proteins; D013792:Thalidomide