Steroids and Cancer TreatmentGlucocorticoids have been used in clinical oncology for over half a century. The clinical applications why are steroids given in cancer treatment glucocorticoids in oncology are mainly dependent on their pro-apoptotic action to treat lymphoproliferative disorders, and also on alleviating side effects induced by chemotherapy or radiotherapy in non-hematologic cancer types. Researches d-box ????-box ??? the past few years have begun to unveil the profound complexity of glucocorticoids signaling and have contributed remarkably on therapeutic strategies. However, it remains striking and puzzling how glucocorticoids use different mechanisms in different cancer types and different targets to promote or inhibit tumor progression. In this review, we provide an update on glucocorticoids and its receptor, GR-mediated signaling and highlight some of the latest findings on the actions of glucocorticoids cancerr during tumor progression and metastasis.
New dimension of glucocorticoids in cancer treatment - ScienceDirect
We've noticed that you're using an ad blocker Our content is brought to you free of charge because of the support of our advertisers. To continue enjoying our content, please turn off your ad blocker. Despite the fact that there are only a few controlled trials demonstrating the benefits associated with the use of corticosteroids in specific situations, these agents are administered frequently to patients with advanced cancer.
Corticosteroids may be used alone or as adjuvants in combination with other palliative or antineoplastic treatments. For example, corticosteroids may help prevent nausea, vomiting, and hypersensitivity reactions to treatment with chemotherapy or radiation. They are also commonly used as appetite stimulants in patients with advanced cancer. In the adjuvant setting, corticosteroids help to alleviate pain in advanced cancer patients, including specific situations such as back pain related to epidural compression.
This article reviews the evidence supporting the use of corticosteroids in a broad range of situations seen in patients with advanced cancer. C orticosteroids are commonly used in the treatment of patients with advanced cancer. However, much of this use stems from the experience of practitioners rather than from data collected in controlled clinical trials. This article will review the available evidence on the use of corticosteroids in advanced cancer, including treatment of refractory malignancies, use as premedication with chemotherapy, and symptom palliation.
The most commonly used corticosteroids in the United States include prednisone, prednisolone, methlyprednisolone, dexamethasone, and hydrocortisone, all of which were approved by the Food and Drug Administration in the s. There does not appear to be evidence to support the use of one corticosteroid over another in any given situation, although physicians have their preferences. Corticosteroids exhibit varying glucocorticoid and mineralocorticoid effects Table 1.
Corticosteroids inhibit inflammatory and immune responses, most likely through alteration of cellular transcription and protein synthesis as well as through effects on lipocortins, which inhibit the release of arachidonic acid. The use of corticosteroids in advanced cancer revolves around their glucocorticoid effects, combined with an avoidance of the salt-retaining properties that characterize mineralocorticoids.
That said, it is important to remember that patients previously treated with corticosteroids may have some degree of adrenal suppression and, therefore, may require supplemental corticosteroid therapy during stressful situations. In this setting, mineralocorticoid properties are desired.
Chronic use of corticosteroids causes adrenal suppression and may blunt or prevent normal adrenal response to physiologic stress. To avoid this effect, many cancer patients may receive intermittent doses of steroids as antiemetics to prevent hypersensitivity reactions, or as adjuvants for pain control.
Spiegel and colleagues performed adrenocorticotropic hormone ACTH -stimulation tests in 14 patients receiving high-dose prednisone for emesis prophylaxis prior to chemotherapy. Investigators at the University of Rochester performed ACTH-stimulation tests in nine women with ovarian cancer before and during chemotherapy in which dexamethasone premedication was used.
It is probably not necessary to taper steroids when they are administered in brief, intermittent doses, but adrenal suppression should be considered when patients who have received such treatment present with hypotension and severe illness. The use of replacement-dose steroids in patients with cancer who are undergoing surgery was recently reviewed by Lefor. The risks associated with corticosteroid use in patients with advanced cancer have been reviewed extensively. Side effects from chronic use include development of a cushingoid appearance, weight gain, edema, cataracts, osteoporosis, proximal myopathy, thinning of the skin, infection, and impaired wound healing.
Corticosteroids can also lead to neuropsychiatric changes including depression, agitation, and delirium. It is important, therefore, to carefully weigh the potential benefits of corticosteroid therapy against potential side effects, and to closely monitor the efficacy of therapy. If no improvement is noted, treatment should be adjusted or discontinued.
Corticosteroids have been used as anticancer agents since the s, with activity reported in a wide variety of solid tumors, including breast and prostate cancer, and the lymphoid hematologic malignancies.
This section will focus on the use of corticosteroids as palliative anticancer treatment once chemotherapeutic options have been exhausted or abandoned. Several studies have been reported suggesting a benefit with the use of corticosteroids in refractory multiple myeloma.
Alexanian et al reported the use of pulse prednisone therapy in patients with myeloma refractory to melphalan Alkeran. Norfolk and Child performed a similar study in 17 patients with relapsed or refractory disease. An overall improvement in quality of life was also noted.
Notably, two of the nonresponders demonstrated an improvement in performance status. Median survival for the group was more than 19 months. In , the Eastern Cooperative Oncology Group reported a pilot study of high-dose, pulsed dexamethasone in patients with relapsed or refractory disease. The study also reported significant toxicity, with 19 patients experiencing side effects assessed as at least grade 2.
Median survival was 19 weeks, and the authors suggested that less frequent administration at longer intervals should be considered. They measured glucocorticoid receptors from patient samples and found an improved response, but no change in overall survival among patients with a moderate number of receptors, compared with patients with a low number of receptors. Prednisone, as used in this study, was well tolerated and appeared to be associated with response and median survival rates 12 months similar to those reported with other drug schedules used in myeloma.
However, the patients died 14 and 15 months after initiation of therapy with prednisone. The majority of patients received prednisolone, 15 mg daily, and 10 patients received hydrocortisone acetate, 75 mg daily. There was no correlation with any prior response to endocrine therapy, and toxicity was felt to be acceptable. Unfortunately, the authors did not report a clinical benefit as subjectively reported by the patients.
Mercer and colleagues reported a prospective randomized trial of aminoglutethimide Cytadren, mg twice daily vs hydrocortisone 20 mg twice daily in advanced breast cancer. Of 61 patients entered into the trial, 56 were included in the analysis. Although this difference was not statistically significant, it does serve as evidence that corticosteroids have activity in breast cancer. The authors did not report on clinical benefit. Hormone therapy is well established in the treatment of prostate cancer.
However, progressive disease after failure of hormone therapy is a difficult problem for patients in this setting. Tannock and colleagues from the Princess Margaret Hospital in Toronto have reported their experience with prednisone in the treatment of hormone-refractory disease.
Pain scores were assessed by three different measures at monthly intervals. Responses did not correlate with alkaline or acid phosphatase measures, but did appear to correlate with suppression of adrenal androgens. Although the median duration of response was only slightly more than 4 months, the investigators concluded that there was improvement in quality of life with little toxicity or expense.
These investigators have now reported on the superiority of the combination of mitoxantrone Novantrone and prednisone as palliation for a similar group of patients; however, this therapy was not associated with a survival advantage. Sartor and colleagues assessed the effects of prednisone, 10 mg twice daily, on prostate-specific antigen PSA in 29 men with progressive, hormone-refractory prostate cancer. The median progression-free survival was 2 months; however, median overall survival was The duration of symptom control and any correlation with PSA measurements were not reported, but would be of interest as patients lived an average of 10 months beyond the development of progressive disease.
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