Role of Corticosteroids Unclear for Men With mCRPC

Beth Fand Incollingo @fandincollingo
Published: Friday, Jan 31, 2014

William K. Oh, MD

William K. Oh, MD

Prednisone, when used in concert with other therapies for the treatment of metastatic castration-resistant prostate cancer (mCRPC), does not raise the risk for severe toxicities, nor does it affect overall survival (OS), researchers found in a meta-analysis1 presented during the 10th Annual Genitourinary Cancers Symposium in San Francisco, California.

In prostate cancer, the corticosteroid, an anti-inflammatory that also suppresses the immune system, is routinely given with chemotherapy drugs docetaxel, cabazitaxel, and mitoxantrone, as well as with abiraterone, a recently approved androgen biosynthesis inhibitor, in which prednisone can mitigate side effects such as hypertension. Prednisone is used in prostate cancer for its direct and indirect anti-cancer effects, including the lowering of prostate-specific antigen; for its quality-of-life benefits, including appetite stimulation; and because it was historically used to accompany mitoxantrone, and the practice was carried over to treatment with docetaxel when that drug was later approved for use in the disease, said two authors of the study, Matthew D. Galsky, MD, and William K. Oh, MD, in interviews with OncLive.

Galsky, associate professor of Medicine at Mount Sinai’s Icahn School of Medicine in New York City and director of the Genitourinary Medical Oncology Program at the Tisch Cancer Institute, said that he and his co-investigators initiated the study because the role of prednisone in the treatment of men with advanced prostate cancer has been controversial, and it remains unclear whether steroids are needed, or provide benefit, in this group.

Further, Galsky said, prior biologic evidence showed that prednisone might be harmful in certain populations of men with prostate cancer. He gave as an example a recent preclinical study by Arora et al,2 which demonstrated that steroids given with certain inhibitors of the androgen receptor could actually drive tumor growth in some prostate cancers.

The meta-analysis by Galsky and his colleagues includes five randomized trials that investigated grade ≥3 toxicities and survival outcomes associated with prostate cancer treatment regimens administered with and without prednisone. The studies were conducted between January 1996 and June 2013.

One trial compared docetaxel/prednisone against docetaxel/DN101; another compared docetaxel/prednisone against GVAX; and a third pitted docetaxel/prednisone against docetaxel/GVAX. A fourth trial compared prednisone against flutamide, and the fifth compared mitoxantrone/prednisone against docetaxel/estramustine phosphate.

In all, there were 2939 patients in those studies, about half of them receiving prednisone. All five studies were rolled into the analysis of toxicities, and four were included in the OS analysis; the flutamide study was excluded because it did not have the required parameters.

The investigators found no difference between the prednisone and non-prednisone groups when it came to severe toxicities (incidence rate ratio = 0.82, P = .712, I2 = 97.9%). Patients in both groups faced the same risk of discontinuing therapy due to toxicities (relative risk = 1.24, P = .413, I2 = 86.8%), the authors reported.

The non-prednisone groups demonstrated no difference in OS compared to the prednisone groups (hazard ratio = 1.09, P = .531, I2= 79.7%).

The results do not exclude the possibility that prednisone had a favorable palliative benefit for patients, the authors wrote.

“We showed that giving steroids doesn’t clearly lead to a detriment in outcomes in men with prostate cancer in the specific clinical disease states tested. That doesn’t mean that a subset of patients, based on the mechanism by which their tumors are progressing, might not be harmed by steroids,” Galsky pointed out. “That needs to be the subject of further studies to identify: 1) Are there any patients who actually benefit from the steroid use, aside from side-effect mitigation with abiraterone? and 2) Can we identify patients whom we are actually hurting by giving prednisone?”

Patients with comorbidities such as diabetes, fluid retention, or congestive heart failure might be among those whose conditions could be worsened by prednisone, noted Oh, professor of Medicine, Hematology, and Medical Oncology at Mount Sinai Hospital. “But that said, I don’t think that, by itself, prednisone is necessarily a dangerous drug,” he said, “and it has some positive effects we have to be aware of.”

Still, Galsky cautioned, there are more questions to be answered about the issue.

“Whether or not giving steroids with drugs in different disease settings is harmful at all is not clear,” he said. “In general, whether or not steroids help, hurt, or do neither depends on the individual patient and the individual tumor biology, and is much more complex than we initially thought.”


References
  1. Naik G, Morgan C, Galsky MD, Oh WK, Sonpavde G. Meta-analysis of randomized trials to study the impact of prednisone on toxicities and survival in metastatic castration-resistant prostate cancer. Presented at: the 10th Annual Genitourinary Cancers Symposium; January 30-February 1, 2014; San Francisco, California.
  2. Arora VK, Schenkein E, Murali R, et al. Glucocorticoid receptor confers resistance to antiandrogens by bypassing androgen receptor blockade. Cell. 2013;155(6):1309-1322.
     





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Community Practice Connections™: Personalized Sequencing in Castration-Resistant Prostate Cancer: Bridging the Latest Evidence to the Bedside in Clinical ManagementAug 25, 20181.5
Community Practice Connections™: Precision Medicine for Community Oncologists: Assessing the Role of Tumor-Testing Technologies in Cancer CareNov 30, 20181.0
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