BACKGROUND: Prednisone is an active drug in the treatment of multiple myeloma. The optimal dose, frequency, and role of glucocorticoid receptors (GR) in response to prednisone is unknown. PURPOSE: The purposes of this study were (1) to estimate the response rate of alternate-day high dose prednisone in patients with relapsing and refractory multiple myeloma; (2) to measure the rate of GR levels; and (3) to correlate the response of prednisone with GR status. PATIENTS AND METHODS: Between 8/86 and 1/90, 127 patients were entered onto the study with 121 evaluable for response. The number of GR sites/cell was determined on mononuclear cells isolated from pretreatment bone marrow aspirates using a one point GR binding assay. Patients received prednisone 100 mg po qod x 2 weeks, followed by 50 mg po qod x 10 weeks. RESULTS: The overall response rate was 10% (95% CI: 5-15%) with a median survival of 11.8 months. The GR sites/cell ranged from 0-53,212 with a mean of 8,371 sites/cells. Stratification of GR sites into 0-2,500, 2,501-6,000 and > 6,000 sites/cells was associated with a response rate of 6%, 27% and 4% respectively (p = 0.009). The median survival of patients in these categories was 8.1, 14.9 and 10.6 months respectively. This was not significant by the logrank test (p = 0.11). Although myeloma patients with intermediate levels of GR sites/cell initially responded more favorably to prednisone, their long-term survival was not significantly improved. CONCLUSIONS: Alternate-day high-dose prednisone was well tolerated and may provide palliative benefit for a subset of patients with relapsing and refractory multiple myeloma. The survival of patients on this study was comparable to that reported with other but more toxic doses of glucocorticoids.
BACKGROUND:Prednisone is an active drug in the treatment of multiple myeloma. The optimal dose, frequency, and role of glucocorticoid receptors (GR) in response to prednisone is unknown. PURPOSE: The purposes of this study were (1) to estimate the response rate of alternate-day high dose prednisone in patients with relapsing and refractory multiple myeloma; (2) to measure the rate of GR levels; and (3) to correlate the response of prednisone with GR status. PATIENTS AND METHODS: Between 8/86 and 1/90, 127 patients were entered onto the study with 121 evaluable for response. The number of GR sites/cell was determined on mononuclear cells isolated from pretreatment bone marrow aspirates using a one point GR binding assay. Patients received prednisone 100 mg po qod x 2 weeks, followed by 50 mg po qod x 10 weeks. RESULTS: The overall response rate was 10% (95% CI: 5-15%) with a median survival of 11.8 months. The GR sites/cell ranged from 0-53,212 with a mean of 8,371 sites/cells. Stratification of GR sites into 0-2,500, 2,501-6,000 and > 6,000 sites/cells was associated with a response rate of 6%, 27% and 4% respectively (p = 0.009). The median survival of patients in these categories was 8.1, 14.9 and 10.6 months respectively. This was not significant by the logrank test (p = 0.11). Although myelomapatients with intermediate levels of GR sites/cell initially responded more favorably to prednisone, their long-term survival was not significantly improved. CONCLUSIONS: Alternate-day high-dose prednisone was well tolerated and may provide palliative benefit for a subset of patients with relapsing and refractory multiple myeloma. The survival of patients on this study was comparable to that reported with other but more toxic doses of glucocorticoids.
Authors: H Ishikawa; H Tanaka; K Iwato; O Tanabe; H Asaoku; M Nobuyoshi; I Yamamoto; M Kawano; A Kuramoto Journal: Blood Date: 1990-02-01 Impact factor: 22.113
Authors: M Karl; S W Lamberts; S D Detera-Wadleigh; I J Encio; C A Stratakis; D M Hurley; D Accili; G P Chrousos Journal: J Clin Endocrinol Metab Date: 1993-03 Impact factor: 5.958
Authors: S A Fuqua; S D Fitzgerald; G C Chamness; A K Tandon; D P McDonnell; Z Nawaz; B W O'Malley; W L McGuire Journal: Cancer Res Date: 1991-01-01 Impact factor: 12.701