BMC Cancer 2008, 8:84 http://www.biomedcentral.com/1471-2407/8/84 Table 3: Glucocorticoid Monotherapy Activity in Phase l and Phase ll (Nonrandomized) Trials Author [reference], Year Patient Characteristics Treatment Responses Mass [63], 1964 Moertel et al [64], 1964 Johnson et al [65], 1966 Ramirez et al [66], 1971 32 lung cancer (17 epidermoid, 7 adenocarcinoma, 8 25–100 mg flurometholone po per day None undifferentiated) 26 GI, 18 GU, 7 melanoma, 2 breast for 7 weeks followed by taper 18 colon, 13 gastric, 9 pancreatic, 5 carcinoid, 12 25 mg fluorometholone po every 12 hr 4 PR (1 colon, 1 gastric, 2 primary primary unknown (presumed GI), 6 miscellaneous GI, 1 for at least 2 months unknown) renal cell 44 melanoma, 9 lung carcinoma, 5 ovary, 4 uterus, 4 200–600 mg of NSC-17256 per day po melanoma (3 CR, 2 PR) prostate, 4 kidney, 4 breast, 7 miscellaneous for 8 weeks 24 head and neck, 1 gastric, 36 colorectal, 2 pancreas, 200–600 mg of NSC-17256 per day po Head and neck (1 PR), breast (1 CR, 8 PR), 13 lung, 70 breast, 36 cervix, 12 uterus, 9 ovary, 9 for 6 weeks; average dose 300 mg per uterus/cervix (2 PR), ovary (1 PR), prostate prostate, 27 kidney, 2 bladder, 111 melanoma, 1 day (1 CR, 3 PR), melanoma (6 PR), Hodgkin (1 thyroid, 6 liver, 29 sarcoma, 11 primary unknown, 1 PR) lymphoma, 7 miscellaneous Randomized Controlled Trials of Glucocorticoids in the Endocrine Therapy of Breast Cancer in the Adjuvant Setting In this setting, there are trials of endocrine therapy +/- glu- cocorticoids and trials of glucocorticoid monotherapy compared to no therapy: they are summarized in Table 5. The trials of endocrine therapy +/- glucocorticoids consist of two trials of tamoxifen +/- glucocorticoids in postmen- opausal women; these trials are negative [6,9]. This is con- sistent with the results from the advanced breast cancer setting. In the first of the two trials of glucocorticoid mono- therapy, glucocorticoids weren't beneficial in the post- menopausal group; they might have been beneficial in the premenopausal group, who were treated with ovarian irradiation [44]. In the second trial of glucocorticoid mon- otherapy, premenopausal women were randomly treated with chemotherapy or ovarian ablation followed by a sec- ond randomization to glucocorticoids versus no glucocor- ticoids. Regardless of whether a woman received chemotherapy or ovarian ablation, glucocorticoids were not beneficial. In the 81% of patient in whom ER status was known, chemotherapy tended to be more effective than ovarian ablation in those with low ER concentrations whereas the opposite was true in those with higher ER concentrations. No such relationship was noted when the no prednisolone/prednisolone arms were compared [13]. One feature that complicates interpretation of the second trial is that glucocorticoids were started at the time of oophorectomy or at the start of chemotherapy, and were to be given for 5 years unless relapse occurred. Those in the chemotherapy arm got glucocorticoids during their 24 weeks of chemotherapy. This means that this trial could also be considered a chemotherapy +/- glucocorticoids trial. Glucocorticoid administration resulted in less bone marrow suppression during chemotherapy [13]. Randomized Controlled Trials of Chemotherapy +/- Glucocorticoids in Advanced Breast Cancer There are eight trials of chemotherapy +/- glucocorticoids in advanced breast cancer [16,17,21,25,28,31,40,48]; results are presented in Table 6. Decreased thrombocyto- penia [21,40] and increased administered chemotherapy dose [21,40,48] were associated with glucocorticoid administration in several of these trials. In six of these trials, response rates are given; in four of these trials, survival data is given. It was felt that there was enough similarity in these trials to perform meta-analyses. Meta-analyses of response rates and survival are presented in Figures 3 and 4 respectively. The addition of glucocor- ticoids to chemotherapy in the advanced breast cancer set- ting resulted in an increased response rate. However, there was no effect on one year survival. Randomized Controlled Trials of Chemotherapy +/- Glucocorticoids of Breast Cancer in the Adjuvant Setting There are two trials in this category. Both are relatively large trials of CMF+/-prednisone, and both are negative. This is consistent with what has been found in the advanced breast cancer setting. At the time of enrolment, none of the participants were postmenopausal. In com- parison to trials that enroll postmenopausal women, this might lessen the possible impact of glucocorticoids as endocrine therapy. However, many women on these trials subsequently developed amenorrhea. In the trial of Tormey et al, 20% subsequently became postmenopausal. In the trial of the Ludwig Breast Cancer Study Group, 85% subsequently became postmenopausal. A description of these trials is given in Table 7[12,53,85]. As in the randomized controlled trials of chemotherapy +/ - glucocorticoids in the advanced breast cancer setting, there is evidence of decreased leukopenia [53], decreased thrombocytopenia [12], increased chemotherapy dose [53], and increased chemotherapy dose intensity [12] in the glucocorticoid arms. Page 5 of 19 (page number not for citation purposes)