BMC Cancer 2008, 8:84 http://www.biomedcentral.com/1471-2407/8/84 Table 1: Case Series of Glucocorticoid Monotherapy Author [reference], Year Patient Characteristics Treatment Responses Postlethwait et al [68], 1951 de Camp [69], 1961 Plengvanit and Viranuvatti [70], 1964 Bruera et al [67], 1985 4 gastric, 1 rectal, 1 gallbladder, 1 300 mg IM of cortisone on day 1, 200 mg no objective improvement esophageal, all advanced stage IM on day 2 then 100 mg IM daily for 21 days; one patient received 150 mg instead of 100 mg 255 bronchogenic carcinoma, 19 primary patients received 30–40 mg of prednisone/ no effect, either positive or negative lung tumors of other origins (sarcoma, prednisolone per day, which was tapered adenomatosis etc.), 6 alveolar cell to 10–15 mg per day (occasionally to 5 mg carcinoma of lung, 14 with cancer per day) or 4 mg of dexamethasone per metastatic to lung, 26 pleural carcinoma, 2 day tapered to 1–1.5 mg per day pericardial carcinoma 7 primary carcinoma of the liver 40–60 mg of daily prednisone for 2 weeks little value as based on effect on pain and to 10 months liver size (by physical examination) 8 colon, 7 breast, 4 lung, 4 soft tissue methyprednisolone 16 mg po twice daily no tumor regression sarcoma, 2 kidney, 2 prostate, 1 head and for 25 out of 34 days neck, 1 melanoma, 1 pancreas, 1 ovarian the 24 responses were in breast and prostate cancer with the 2 complete responses being in breast and prostate can- cer [66]. The next largest trial was 94 patients with no responses [63]. The phase l/ll (nonrandomized) clinical trials are presented in Table 3. The two glucocorticoids used in these clinical trials were fluorometholone and NSC-17256. Fluorometholone may have progestational properties [22]. One hundred mg of NSC-17256 is equivalent to 50–67 mg of prednisone; however, it also has sex steroid properties. With regards to quality, all the clinical trials were from ter- tiary care centers. All clinical trials had more than 50 patients. Three of the four trials were multi-institutional [63,65,66]. One of the trials did not describe eligibility criteria [65]. In one trial, patients were similar with regards to the state of cancer progression; in the other tri- als, not enough information was provided to assess simi- larity [64]. In two trials, followup was long enough to assess whether glucocorticoids could cause cancer to regress in size; in the other two trials, it was unclear if fol- lowup was sufficient to assess this [64,66]. Reduction in tumor size was assessed using objective criteria in three of the studies [64-66]; this was unclear in the other study. Table 2: Relative Glucocorticoid Activities of Glucocorticoids Cortisol (Hydrocortisone) Cortisone Prednisone Prednisolone Methylprednisolone Dexamethasone Glucocorticoid Activity 1 0.8 4 4 5 30 Randomized Controlled Trials of Glucocorticoids in the Endocrine Therapy of Advanced Breast Cancer There are two types of trials in this category. In the first type, glucocorticoids are given as monotherapy and com- pared to other endocrine therapies given as monotherapy. There are ten trials of this type, which tend to be small and often use endocrine therapies that are no longer given. In these trials, the vast majority of patients were postmeno- pausal or enrolment was limited to postmenopausal patients. The results show that glucocorticoids have mod- est activity in postmenopausal women. A description of these trials is given in Table 4[5,15,18,19,22,38,47,55,56]. The three earliest trials used response criteria that are not readily comparable to presently used response criteria [5,19,22]. The second type of trial is of an endocrine agent +/- gluco- corticoids. These trials tend to be larger, more recent and limited to women who are postmenopausal or who received ovarian irradiation. There are four trials in this category: three are of tamoxifen +/- glucocorticoids and one is of aminoglutethimide +/- glucocorticoids. Results are presented in Table 4[7,24,37,46]. As these trials were more similar in nature, meta-analyses of response rates and survival were undertaken. As seen in Figure 1, the addition of glucocorticoids to another endocrine therapy resulted in an increased response rate. Figure 2 shows that this addition does not change one year survival rates. However, there was evidence for a lack of homogeneity among the four studies in Figure 2, as shown by the chi- square test and its p value. The meta-analysis was repeated, except that the trial which was furthest from the other three trials in response rate and survival was omitted [24]. The result of the omission was that the addition of glucocorticoids did not change one year survival rates, although the lack of homogeneity disappeared (odds ratio of 0.91 95% CI 0.77–1.08, X22 = 3.389 p = 0.184). One unpublished trial of hormonal therapy +/- glucocor- ticoids, with no available results, was found [72]. Page 4 of 19 (page number not for citation purposes)