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Title:
Efficacy of prednisone in refractory multiple myeloma and measurement of glucocorticoid receptors | Investigational New Drugs
Description:
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 range 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: 5β15%) with a median survival of 11.8 months. The GR sites/cell ranged from 0β53,212 with a mean of 8,371 sites/cells. Stratification of GR sites into 0β2,500, 2,501β6,000 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.
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google, scholar, myeloma, glucocorticoid, multiple, prednisone, cancer, receptors, article, human, response, patients, thompson, cells, res, receptor, refractory, survival, leukemia, privacy, cookies, content, access, blood, data, publish, search, study, phase, dose, rate, levels, binding, highdose, resistance, acute, vitro, cell, dexamethasone, interleukin, information, log, journal, research, drugs, gupta, stocknovack, salmon, bonnet, treatment,
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alternate-day high-dose prednisone month download article/chapter intermittent high-dose predisone high dose chemotherapy gr sites/cell ranged single-agent steroid trial donna stock-novack vitro glucocorticoid studies high-dose glucocorticoid treatment related subjects arizona cancer center steroid hormone resistance privacy choices/manage cookies alpha omega publishing statistical methods based refractory multiple myeloma human multiple myelomas aggressive multiple myeloma thein vitro responses full article pdf cell cycle position high-dose dexamethasone gr sites/cell single point mutation leukaemic human leukocytes distinct receptor phenotypes isolated human leukemia long-term survival acute lymphoblastic leukemia phase ib trial dose intensity analysis european economic area mononuclear cells isolated provide palliative benefit leukemic sezary cells myelomonocytic leukemic cells seventh tenovus workshop exact significance levels cornwell iii gg zinc finger mutations alter domain interaction o'malley bw constitutive transcriptional activity texas medical branch relapsing multiple myeloma acute myelogenous leukemia conditions privacy policy glucocorticoid binding proteins detera-wadleigh sd brad thompson
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headline:Efficacy of prednisone in refractory multiple myeloma and measurement of glucocorticoid receptors
description:
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 range 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: 5β15%) with a median survival of 11.8 months. The GR sites/cell ranged from 0β53,212 with a mean of 8,371 sites/cells. Stratification of GR sites into 0β2,500, 2,501β6,000 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.
datePublished:
dateModified:
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keywords:
multiple myeloma
glucocorticoid receptors
prednisone
Oncology
Pharmacology/Toxicology
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headline:Efficacy of prednisone in refractory multiple myeloma and measurement of glucocorticoid receptors
description:
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 range 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: 5β15%) with a median survival of 11.8 months. The GR sites/cell ranged from 0β53,212 with a mean of 8,371 sites/cells. Stratification of GR sites into 0β2,500, 2,501β6,000 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.
datePublished:
dateModified:
pageStart:121
pageEnd:128
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multiple myeloma
glucocorticoid receptors
prednisone
Oncology
Pharmacology/Toxicology
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