BMC Cancer 2008, 8:84 http://www.biomedcentral.com/1471-2407/8/84 There are two trials of preoperative glucocorticoids in patients scheduled to undergo esophagectomy; there was no effect on survival [51,58]. A description of the GI trials is given in Table 9. Randomized Controlled Trial of Glucocorticoids in Patients with Primary CNS Neoplasms The one RCT of glucocorticoids in primary CNS neo- plasms is described in Table 10. This trial uses a higher dose of glucocorticoids than any other trial described in this review; however, administration was on an intermit- tent, rather than a continuous, basis. This trial compared methyprednisolone versus BCNU versus BCNU plus methylprednisolone versus procarbazine. The addition of methylprednisolone to BCNU had a neutral effect on sur- vival. Infection was significantly greater in the BCNU plus methylprednisolone arm than the other arms; informa- tion on the type and severity of infection is not available. The mean number of courses of chemotherapy was iden- tical in the BCNU and BCNU + methylprednisolone arms. The mean radiotherapy dose +/- SE (rads) was 5701 +/- 79 in the methylprednisolone arm and 5589 +/- 96 in the BCNU + methylprednisolone arm [23]. Randomized Controlled Trials of Glucocorticoids in Patients with GU Neoplasms No trials were found in this category. Randomized Controlled Trials and Meta-analysis of Glucocorticoids in Patients with a Variety of Cancers There are five randomized controlled trials of glucocorti- coid monotherapy in patients with a variety of cancers; these trials are dissimilar in nature. The first two trials used glucocorticoid doses higher than any other trial in this review, with the exception of the pre- viously mentioned randomized controlled trial in CNS neoplasms. However, glucocorticoid administration was continuous in these two trials. Also, administration was intravenous; the bioavailability of oral methypred- nisolone is 82% [88]. The two trials are very similar, except that enrolment was limited to females with the sec- ond trial [30,39]. With this in mind, a survival meta-anal- ysis was performed, with the results presented in Figure 5. Figure 5 shows that this high dose continuous gluccorti- coid schedule had a detrimental effect on mortality. In the first trial, the cause for the difference in mortality was unknown. In the second trial, there were significantly more gastrointestinal and cardiovascular adverse events in the glucocorticoid arm; the severity and outcome of these events did not significantly differ. Infectious complica- tions occurred in 11.8% of the treated patients and 14.8% of the placebo patients [39]. The third trial consists mostly of GI patients, and com- pared indomethacin to prednisolone to placebo. The results suggest that prednisolone might have a beneficial effect on survival [14]. The fourth trial compares a progestational agent to dex- amethasone to an androgen; no difference in survival was observed. The patients were mostly lung and GI cancer patients. Fifty three percent and twenty percent of the patients had planned concurrent chemotherapy and radi- ation therapy respectively. The fifth trial compares opioids to opioids plus dexame- thasone; no survival difference was found. This was a Table 9: Randomized Controlled Trials of Glucocorticoids in GI Cancer Author [reference], Year Patient Characteristics Quality Score Outcome(s) Moertel et al [26], 1974 Reitemeier et al [20], 1967 Kemeny et al [11], 1992 Sato et al [51], 2002 Yano et al [58], 2005 GI cancer with expected survival of less than 2 months (61 colorectal, 22 gastric, 15 pancreatic, 9 hepatoma, 10 other) advanced GI cancer (37 gastric, 23 pancreatic, 52 unknown but presumed GI in origin) untreated colorectal cancer with only metastases being in liver Treatment Arms Patient Number (Randomized/Evaluable) placebo (47/NR) vs. dexamethasone 0.75 mg four times daily (33/NR) vs. dexamethasone 1.5 mg four times daily (36/ NR); treatment until death or patient unable to take pills fluorometholone 25 mg po every 12 hour for at least 2 months (34/32) vs. 5-FU IV 15 mg/kg/day for 5 consecutive days then 7.5 mg/kg/day every other day for a maximum of 4 additional doses (40/40) vs. 5-FU plus fluorometholone as just described (38/32) hepatic arterial FUDR 0.3 mg/kg/day for 14 of every 28 day cycle (25/25) vs. same plus hepatic arterial dexamethasone 20 mg over 14 days with the FUDR (25/24) patients with esophageal squamous cell carcinoma scheduled to undergo esophageal resection surgery (33/33) vs. surgery + 10 mg/kg methyprednisolone IV within 30 minutes of start of surgery (33/33) patients with thoracic esophageal cancer scheduled for esophagectomy surgery (20/20) vs. surgery + methylprednisolone 500 mg IV 2 hours before surgery (20/20) 3 3 3 5 3 Median survival (weeks) of 6.6 vs. 6.2 vs. 5.2 response rates of 9% vs. 13% vs. 13%; average duration of response of 4 vs. 6.5 vs. 4 months response rates of 40% vs. 71% (p = 0.03), median time to progression of 12 vs. 19 months (p = 0.58), median survival of 15 vs. 23 months (p = 0.06) p = 0.4465 for difference in overall survival rates 1 and 3 yr survival rates of 85% and 65% vs. 82% and 62% respectively p = 0.3304 for difference in survival rates Page 11 of 19 (page number not for citation purposes)