BMC Cancer 2008, 8:84 http://www.biomedcentral.com/1471-2407/8/84 Table 11: Randomized Controlled Trials of Glucocorticoids and Meta-analysis in Patients with a Variety of Cancers Quality Score Outcome(s) Author [reference], Year Della Cuna et al [30], 1989 Popiela et al [39], 1989 Lundholm et al [14], 1994 Mercadante et al [61], 2007 Feuer et al [62], 1999, Metaanalysis advanced cancer patients on strong opioids patients with bowel obstruction due to malignancy; vast majority either gynecological or GI cancer glucocorticoids (65/54) vs. no glucocorticoids (32/29) Patient Characteristics preterminal carcinoma; male (196): 38.8% lung, 12.8% stomach, 11.2% buccal cavity and pharynx, 7.1% prostate, 5.1% rectum/rectosigmoid junction female (207): 34.8% breast, 10.1% stomach, 11.1% large intestine, 7.7% cervix uteri, 5.3% lung, 5.3% rectum/rectosigmoid junction terminal cancer, female, 85% with gastrointestinal or breast or genitourinary cancers, only solid tumors liver/pancreas 44, colorectal 30, gastric 18, esophagus 15, melanoma 7, breast 3, head and neck 3, miscellaneous 15 Loprinzi et al [49], 1999 40% lung cancer, 36% GI cancer, no breast or prostate or ovarian or endometrial cancer; Horton et al [27], 1966 19 colorectal cancers, 13 adenocarcinomas of other primary sites, 10 miscellaneous cancers Bernhardt et al [52], 2006 cancers of lung (9), prostate (7), pancreas (3), ovary (2), breast (1), other (4) Sorensen et al [29], 1994 Graham et al, [57], 2006 patients with compression of spinal cord or cauda equina due to cancer: 34 breast cancers, 6 GI cancer, 5 prostate cancer, 3 lung cancer, 4 sarcoma, 2 melanoma, 1 each of kidney, mesothelioma and thyroid patients with spinal cord compression not due to lymphoma or myeloma: 11 breast or prostate cancer, 9 lung or GI or renal or other Randomized Controlled Trials of Glucocorticoids in Lung Cancer There are two randomized controlled trials of glucocorti- coid monotherapy in lung cancer [10,41,42], with both being described in Table 12. In the first trial, those in the glucocorticoid arm did worse than those in the placebo arm. As causes of death, rates of pulmonary infection, hemorrhage, heart failure and perforated ulcer were very similar between the placebo and cortisone arms. The authors stated that they were unable to explain why the cortisone arm did worse [41]. In a later publication regarding this trial, it is noted that results were not differ- ent between patients, who had received prior to the trial, surgery, radiation therapy or who hadn't received either therapy. Although it is unclear how systematically this was studied, the authors did not observe a difference in the rate of cancer progression between the placebo and corti- sone arms based on x-ray and autopsy information [42]. The second trial is a comparison of prednisolone versus megestrol acetate; those in the megestrol acetate arm did significantly worse [10]. As mentioned in Table 12, no radiation with a curative intent or chemotherapy was Treatment Arms Patient Number (Randomized/Evaluable) methylprednisolone 125 mg IV daily for 8 weeks (207/NR) vs. placebo (196/NR) methylprednisolone 125 mg IV daily for 56 days (85/NR) vs. placebo (88/NR) indomethacin 50 mg po twice daily (45/NR) vs. prednisolone 10 mg po twice daily (45/ NR) vs placebo (45/NR); all treatments until death megestrol acetate 800 mg po every day (NR/158) vs. dexamethasone 0.75 mg po four times daily (NR/158) vs. fluoxymesterone 10 mg po twice daily (NR/ 159) opioids vs. opioids + dexamethasone 8 mg po daily; 76 randomized/66 evaluable 5-FU IV 15 mg/kg on 1st, 2nd, 3rd, 4th and 6th days and 7.5 mg/kg every other day thereafter until diarrhea, stomatitis or leukopenia (21/NR) vs. same + methyprednisolone 24 mg po daily (21/NR) docetaxel 75 mg/m2 day 8 of each 21 day cycle + perifosine 50 mg po 1 or 2 or 3 times a day in successive cohorts on days 1- 14 vs. same + prednisone 5 mg twice daily radiation (30/30) vs. radiation + initial dose of dexamethasone 96 mg IV followed by dexamethasone 96 mg po daily for 3 days followed by 10 day taper (29/27) radiation + 16 mg of dexamethasone intravenously for 3 days followed by 13 day taper (9/9) vs. same except 96 mg of dexamethasone for first 3 days (11/11) 5 5 2 2 2 4 1 2 1 mortality at 8 weeks: males 40.2% vs. 35.5%, females 40.0% vs. 27.7% (p < 0.01) mortality at 56 days of 38% vs. 30% (p > 0.05) when all 3 groups compared simultaneously, survival of indomethacin > prednisone > placebo (p < 0.07) median survival of 126 days with no statistically significant difference between the 3 arms Mean survival (range) of 33 (26-40) vs. 37 (28-45) days Kaplan-Meier survival curves and 1 month survival: no differences of statistical significance response rates of 24% vs. 19% 2 SD (2 prostate) in 7 evaluable patients vs. 3 PR (1 lung and 2 prostate) and 1 SD (prostate) in 9 evaluable patients median survival of 6 months in both arms median survivals of 2.4 vs. 2.1 months given in the second trial (F. Macbeth, personal communi- cation). In lung cancer, there are two randomized controlled trials of chemotherapy +/- glucocorticoids; both are included in Table 12. The first trial was of cyclophosphamide +/-pred- nisolone; the addition of prednisolone resulted in a lower response rate and decreased survival. Of the planned cyclophosphamide doses, 88% were administered in the cyclophosphamide arm and 69% were administered in the combined arm. As for treatment delays, 4 patients were delayed 1–2 weeks with 3 of these being in the cyclo- phosphamide arm. No patient died of treatment in the cyclophosphamide arm, but 3 died of infection in the combined arm. Six patients had infections requiring hos- pitalization in the cyclophosphamide arm, compared to 2 in the combined arm. There was no significant difference in hematologic toxicity between the 2 arms. There was a trend for less leukopenia in the combined arm. In the cyclophosphamide arm, a leukocyte count of less than 1999 cells/mm3 occurred in 43% of patients in cycle 1, 96% in cycle 2 and 100% in cycle 3. In the combined arm, comparable data is 28% in cycle 1, 60% in cycle 2 and Page 13 of 19 (page number not for citation purposes)