Systematic review of the clinical effect of glucocorticoids on nonhematologic malignancy

Abstract

Background: Glucocorticoids are often used in the treatment of nonhematologic malignancy. This review summarizes the clinical evidence of the effect of glucocorticoid therapy on nonhematologic malignancy.

Methods: A systematic review of clinical studies of glucocorticoid therapy in patients with nonhematologic malignancy was undertaken. Only studies having endpoints of tumor response or tumor control or survival were included. PubMed, EMBASE, the Cochrane Register/Databases, conference proceedings (ASCO, AACR, ASTRO/ASTR, ESMO, ECCO) and other resources were used. Data was extracted using a standard form. There was quality assessment of each study. There was a narrative synthesis of information, with presentation of results in tables. Where appropriate, meta-analyses were performed using data from published reports and a fixed effect model.

Results: Fifty four randomized controlled trials (RCTs), one meta-analysis, four phase l/ll trials and four case series met the eligibility criteria. Clinical trials of glucocorticoid monotherapy in breast and prostate cancer showed modest response rates. In advanced breast cancer meta-analyses, the addition of glucocorticoids to either chemotherapy or other endocrine therapy resulted in increased response rate, but not increased survival. In GI cancer, there was one RCT each of glucocorticoids vs. supportive care and chemotherapy +/- glucocorticoids; glucocorticoid effect was neutral. The only RCT found of chemotherapy +/- glucocorticoids, in which the glucocorticoid arm did worse, was in lung cancer. In glucocorticoid monotherapy, meta-analysis found that continuous high dose glucocorticoids had a detrimental effect on survival. The only other evidence, for a detrimental effect of glucocorticoid monotherapy, was in one of the two trials in lung cancer.

Conclusion: Glucocorticoid monotherapy has some benefit in breast and prostate cancer. In advanced breast cancer, the addition of glucocorticoids to other therapy does not change the long term outcome. In GI cancer, glucocorticoids most likely have a neutral effect. High dose continuous glucocorticoids have a detrimental effect in nonhematologic malignancy. Glucocorticoid therapy might have a deleterious impact in lung cancer.

Figure 1

Forest Plot of Response Rates of Endocrine Therapy +/- Glucocorticoids in Advanced Breast Cancer.

Figure 2

Forest Plot of One Year Survival Rates of Endocrine Therapy +/- Glucocorticoids in Advanced Breast Cancer.

Figure 3

Forest Plot of Response Rates of Chemotherapy +/- Glucocorticoids in Advanced Breast Cancer.

Figure 4

Forest Plot of One Year Survival Rates of Chemotherapy +/- Glucocorticoids in Advanced Breast Cancer.

Figure 5

Forest Plot of Eight Week Mortality Rates in Two Trials of Glucocorticoid Monotherapy in Nonhematologic Malignancy.