Author [reference], Year Patient Characteristics Dao et al [19], 1961 Colsky et al [5], 1963 Postmenopausal postmenopausal, previous androgens or estrogens for advanced disease Talley et al [22], 1964 Talley et al [22], 1964 postmenopausal, no previous endocrine therapy postmenopausal, previous androgens or estrogens Gaertner et al [18], 1968 Postmenopausal 81% postmenopausal, 40.5% ER and/ aminoglutethimide 1000 mg po daily + or PgR +ve, 26.7% ER/PgR -ve, cortisone acetate 50 mg po daily (65/62) vs. 32.8% ER/PgR unknown aminoglutethimide 1000 mg po daily + MPA 1000 mg po daily (73/69) Kristensen et al, [47] 1992 Hypercalcemia due to breast cancer Goldenberg [15], 1969 Jakobsen et al [38], 1986 Wander et al [56], 1987 Mercer et al, [55] 1993 Stewart et al [24], 1982 Rubens et al [46], 1988 Ingle et al, [7] 1991 Cocconi et al, [37] 1992 postmenopausal, no previous hormonal therapy 95% previous antiestrogen therapy, 83% postmenopausal postmenopausal; PD on tamoxifen (adjuvant or advanced setting) Only previous systemic therapy allowed was adjuvant chemotherapy, 98 ER +ve, 28 ER -ve, 54 ER unknown Only previous systemic therapy allowed was adjuvant chemotherapy (15%): ER/PgR unknown (23%) or ER+ve or PgR+ve postmenopausal; ER/PR unknown (15%) or ER+ve or PgR+ve; only previous systemic therapy allowed was adjuvant chemotherapy (7.8%) postmenopausal; ER/PgR unknown (48%) or ER+ve or PgR+ve; no previous endocrine therapy for advanced disease; previous chemotherapy or endocrine therapy in 39% BMC Cancer 2008, 8:84 http://www.biomedcentral.com/1471-2407/8/84 Table 4: Randomized Controlled Trials of Glucocorticoids in the Endocrine Therapy of Advanced Breast Cancer Quality Score Outcome In one of the trials, there was a significant increase in bone, alone or in combination with other sites, as the site of first relapse in the chemotherapy plus prednisone arm (relative risk of 2.06, 95% CI of 0.91 to 12.31, p = 0.09). The authors postulated that the increased rate of bone metastases as a first relapse site in this arm might be due to cytokine inhibition, which might reduce a putative anti-cancer process in bone, or to increased bone absorp- tion [53]. Randomized Controlled Trials of Glucocorticoids in Prostate Cancer In prostate cancer, there are two RCTs of glucocorticoids in untreated patients [43,59]. Both are trials of orchiec- tomy versus orchiectomy plus glucocorticoids versus orchiectomy plus cyproterone acetate. The small numbers enrolled preclude analysis, other than it is improbable that glucocorticoids worsen outcome when added to Page 6 of 19 (page number not for citation purposes) Treatment Arms and Patient Numbers (Randomized/Evaluable) bilateral adrenalectomy + hormone replacement (19/18) vs. cortisone acetate (at least 3 months; 300 mg on first day tapered to 50 mg daily) (20/19) 100 mg of 9α-bromo-11β-ketoprogesterone po every 8 hrs for at least 60 days (32/23) vs. same except 13.2 mg of prednisolone (23/18) 10 mg of fluoxymesterone (an androgen) po twice daily (23/21) vs. 25 mg of oxylone acetate po twice daily (23/22) 25 mg of oxylone acetate po twice daily (14/ NR) vs. 12 mg of methylprednisolone twice daily (13/NR) dromostanolone propionate (an androgen) 100 mg IM 3 times weekly (22/NR) vs. fluorometholone 25 mg po daily (22/NR) vs both together (24/NR) Testololactone (an androgen) 75 mg twice daily po (103/100) vs. MPA 50 mg twice daily po (108/104) vs. oxylone acetate 25 mg twice daily po (108/107) prednisone 10 mg po three times daily (52/43) vs. MPA 500 mg po daily (48/38) vs. MPA 100 mg IM daily except Sat/Sun for 3 weeks then 500 mg IM weekly(50/40); continued until PD standardized isotonic saline + IV furosemide (15/15) vs. same + prednisolone 25 mg po three times daily for 8 days (15/15) aminoglutethimide 125 mg twice daily (28/27) vs. hydrocortisone 20 mg twice daily (33/29) Premenopausal: ovarian irradiation (19) vs. same + prednisolone 5 mg twice daily (16) Postmenopausal: tamoxifen 10 mg twice daily (72) vs. same + prednisolone 5 mg twice daily (73); treatment until PD; 204 randomized, 180 evaluable Premenopausal: ovarian irradiation with prednisolone 5 mg twice daily added on progression (NR/15) vs. ovarian irradiation + prednisolone 5 mg twice daily until PD (NR/ 16)/Postmenopausal: tamoxifen 10 mg twice daily changed to prednisolone 5 mg twice daily on progression (NR/78) vs. tamoxifen 10 mg twice daily +prednisolone 5 mg twice daily until PD (NR/85); 220 randomized/194 evaluable tamoxifen 10 mg po twice daily (162/159) vs. tamoxifen 10 mg po twice daily + prednisolone 5 mg po twice daily (164/161); continued until PD aminoglutethimide 125 mg po twice daily for 1 month then 250 mg po twice daily (84/78) vs. same + hydrocortisone 20 mg po twice daily (87/83); treatment until PD 1 4 2 4 3 2 1 1 3 2 2 2 5 3 8 vs. 0 remissions 0 vs. 1 remission 3 vs. 6 remissions (ns) 3 vs. 3 remissions 9 vs. 2 vs. 5 responses response rates of 4.9% vs. 9.3% vs. 19.4%; p = 0.052 for MPA and oxylone being equal response rates of 4.6% vs. 7.9% vs. 12.5% (ns), median time to progression of 3 vs. 2.5 vs. 4 months (p = 0.09), median survival of 6 vs. 8.5 vs. 10 months (p = 0.30) response rates (CR/PR) of 6.5%/25.8% vs. 7.3%/24.6% median survival of 40 days vs. 84 days (p = 0.46) response rates in 11% vs. 21% (p > 0.1), time to treatment failure similar (p = 0.743), overall survival similar (p = 0.240) Premenopausal/Postmenopausal response rates: 21% vs. 44% (ns)/13% vs. 36% responses (p < 0.01), median survival 19 vs. 18 months (ns)/12 vs. 21 months (p < 0.025) Premenopausal/Postmenopausal response rates: 27% vs. 63% (p < 0.05)/31%vs46%(p < 0.1), median time to disease progression: 4 vs. 14 months (p = 0.006)/4 vs. 8 months (p = 0.02), median survival: 17 vs. 66 months (p = 0.04)/17.5 vs. 21 months (p = 0.3) responses in 38% vs. 47% (p = 0.15), median time to progression: 11 vs. 10 months (p = 0.81), median survival: 35 vs. 32 months (p = 0.40) responses in 41% vs. 44% (ns), median time to progression: 6.3 vs. 8.1 months (p = 0.38), median survival: 36.3 vs. 34.2 months (p = 0.56)