Author [reference], Year DiMartino et al [9], 1991 Fentiman et al [6], 1994 Meakin et al, [44], 1996 Postmenopausal Postmenopausal Scottish Cancer Trials Breast Group [13], 1993 Premenopausal ER+ve 54%, ER status unknown 19% Tamoxifen 40 mg per day vs. same + prednisolone 7.5 mg per day; 67/57 vs. 49/47; treatment until recurrence Tamoxifen 20 mg daily vs. same + prednisolone 7.5 mg daily; 186/173 vs. 184/168 no further treatment (NT) vs. ovarian irradiation (R) vs. (if ≥ 45) ovarian irradiation + prednisolone 7.5 mg daily up to 5 years (R +P); Premenopausal (≥ 45 years old) 64 vs. 71 vs. 73/Postmenopausal 136 vs. 111 vs. 111; 779 randomized, 703 analyzed as above Second randomization to prednisolone 7.5 mg po daily for 5 years vs. no prednisolone after first randomization to ovarian ablation vs. CMF (IV); 165/NR vs. 167/NR in second randomization 1 2 1 3 p values of 0.6743 and 0.2367 for differences in disease free survival and overall survival respectively p values of 0.26 and 0.32 for differences in relapse free survival and overall survival respectively Premenopausal(≥ 45 years old)/ Postmenopausal; median recurrence free survival (yrs): 9.4 vs. 18 vs. > 25/6.2 vs. 8.2 vs. 6.8; median survival (yrs): 12.8 vs. 14.9 vs. >25/9.3 vs. 9.9 vs. 7.7 prednisolone effect did not depend on whether CMF or ovarian ablation (p = 0.46); hazard ratio and 95% CI for deaths for +/-prednisolone was 1.26 (0.86–1.84) BMC Cancer 2008, 8:84 http://www.biomedcentral.com/1471-2407/8/84 Table 5: Randomized Controlled Trials of Glucocorticoids in the Endocrine Therapy of Breast Cancer in the Adjuvant Setting Patient Characteristics Treatment Arms; Patient Number (Randomized/ Evaluable) Quality Score Outcome(s) glucorticoids are compared to other hormonal therapies (progestational agents and flutamide), little difference was noted. When glucocorticoids were compared to liaro- zole (a retinoic acid stimulating agent), glucocorticoids resulted in a better outcome. In the three oldest trials, the response criteria used are not readily comparable to pres- ently used response criteria [8,33,35]. There is one randomized controlled trial of chemotherapy +/- glucocorticoids in prostate cancer [50]. This small trial Table 6: Randomized Controlled Trials of Chemotherapy +/- Glucocorticoids in Advanced Breast Cancer Author [reference], Year Patient Characteristics Brambilla et al [17], 1974 Postmenopausal Ramirez et al [16], 1975 Rossi et al [25], 1976 Tormey et al [21], 1982 Tormey et al [48], 1983 Pre or postmenopausal, no previous chemotherapy Pre or postmenopausal, no previous chemotherapy or prednisone therapy Pre or postmenopausal, no previous chemotherapy or prednisone therapy Gercovich et al [31], 1989 Untreated Tashiro & Nomura [40], 1995 resistant to or relapsed after adriamycin treatment, pre or postmenopausal Piccart et al [28], 1997 One previous chemotherapy regimen for advanced or metastatic breast cancer Treatment Arms Patient Number (Randomized/Evaluable) adriamycin 40–75 IV mg/m2 day 1, vincristine IV 1.4 mg/m2 days 1 and 8 every 3 weeks for 8 cycles (20/15) vs same + prednisone 100 po mg/m2/day days 1–5 (22/21) 5-fluorouracil (5-FU) 10 mg/kg/week IV, methotrexate 0.5 mg/kg/week IV, vincristine 0.02 mg/kg/week IV, cyclophosphamide 2 mg/kg/day po (NR/52) vs. same + prednisone po 45 mg/day for 2 weeks, then 30 mg/day for 2 weeks then 15 mg/day (NR/ 48); treatment until PD L-phenylalanine 4 mg/m2 po/day + 5-FU 300 mg/m2 po/day each days 1–5 every 28 days (16/14) vs. same except 5-FU IV (18/18) vs. same as first except 5-FU IV + prednisone 30 mg/m2/day days 1–5 (17/15) CMF (NR/79) vs. CMFP (NR/86) vs. AV (NR/166); after 6 months or if progressive disease prior to then, switched to nonglucocorticoid containing chemotherapy CMF (NR/47) vs. CMFP (NR/47) vs. rotation every 2 cycles between CMF and AV (NR/ 50); treatment for 6 months followed by nonglucocorticoid containing therapy 5-FU + cyclophosphamide + mitoxantrone vs. same + prednisone 80 mg po days 1–5 (53/50 in total) mitomycin C 4 mg/m2 + methotrexate 35 mg/m2 IV + vincristine 0.7 mg/m2 IV days 1 and 8 every 21 days (21/21) (MMV) vs. same + prednisolone 10 mg po per day (MMVP) (43/41) vs. same as first + MPA 1200 mg po per day (MMVM) (44/40); treatment until PD docetaxel 50 mg/m2 IV days 1 and 8 every 3 weeks (42/41) vs. same + methylprednisolone 40 mg po on days - 1,0,1,7,8 and 9 (41/39) 2 2 1 1 2 1 2 2 Quality Score Outcome(s) response rates of 50% vs. 55% response rates of 44.2% vs. 62.5% (p = 0.075), no significant difference in response duration or survival response rates of 7% vs. 22% vs. 40% (ns) response rates of 57% vs. 63% vs. 56% (p > 0.10), response durations of 4.5 months vs. 8.4 months vs. 7.7 months (p = 0.05), time to treatment failure of 5.3 months vs. 9.1 months vs. 5.7 months (p = 0.04), overall survival of 14.5 months vs. 16.4 months vs. 13.7 months (p = 0.03) response rates of 55% vs. 70% vs. 58% (ns), response duration of CMF less than CMFP (p = 0.39); time to treatment failure of CMF 5.6 months and CMFP 7.0 months (p = 0.16); median survival of CMF 12.5 months and CMFP 18.0 months no difference in response rates response rates of 9.5% vs. 29% vs. 37.5% (p = 0.0784 comparing MMV to MMVP); median duration of response of 12 vs. 16 vs. 34 weeks (ns); time to progression for MMVM longer than MMVP which was longer than MMV (p = 0.0256); survival differences (p = 0.382) no significant differences in median response duration, median time to progression or median survival Page 8 of 19 (page number not for citation purposes)