{"id":284,"date":"2019-10-10T19:49:35","date_gmt":"2019-10-10T14:19:35","guid":{"rendered":"https:\/\/medicineplexus.com\/?p=284"},"modified":"2019-10-10T19:49:35","modified_gmt":"2019-10-10T14:19:35","slug":"corticosteroids-in-the-treatment-of-neoplasms","status":"publish","type":"post","link":"https:\/\/medicineplexus.com\/corticosteroids-in-the-treatment-of-neoplasms\/","title":{"rendered":"Corticosteroids in the Treatment of Neoplasms"},"content":{"rendered":"\n<p><strong>Corticosteroids in\nthe Treatment of Neoplasms<\/strong><\/p>\n\n\n\n<p><strong>Mechanism\nof Glucocorticoid Action<\/strong><\/p>\n\n\n\n<p>The majority\nof the biologic effects of steroid hormones are mediated by intracellular\nreceptors specific for each class of steroid. <\/p>\n\n\n\n<p>The glucocorticoid receptor (GR), a cytoplasmic protein,\nis present in all tissues that are targets of glucocorticoid action.<\/p>\n\n\n\n<p>Activation of\nGR \u00e0 involve a\nconformational change in GR, increased phosphorylation of the receptor, and\nrelease of associated regulatory proteins. Activated steroid-receptor complex\ntranslocates to the nucleus, binds as a homodimer to specific DNA sequences\ncalled glucocorticoid-responsive elements (GREs), and alters the transcription\nrate of specific genes associated with the GRE. lead to changes in the amount\nof messenger RNA and, ultimately, the level of protein that is synthesized from\nthese genes, and thus alters cellular functions.<\/p>\n\n\n\n<p><strong>Neoplasms Treated with Corticosteroids<\/strong><\/p>\n\n\n\n<p><strong>Acute\nLymphoblastic Leukemia<\/strong><\/p>\n\n\n\n<ul><li>Early studies: (ALL) treated with prednisone alone <strong>showed that 50% of the affected children responded<\/strong> with prompt clinical improvement and <strong>remission.<\/strong><\/li><li>However, remission was short (1 year), and relapse, often coinciding with the appearance of steroid resistance, was inevitable. <\/li><li>For these reasons, multiple drug therapy was initiated, which involves combining prednisone with other cytotoxic agents. <\/li><li>With the advent of regimens that contain vincristine and prednisone or prednisolone, more than 90% of children\u00a0and 60 to 80% of adults\u00a0achieve remission. <\/li><li>In one study, prednisone pretreatment before initiation of combination therapy improved the rate of complete remission in adult patients. <\/li><\/ul>\n\n\n\n<p><strong>Acute\nMyeloid Leukemia<\/strong><\/p>\n\n\n\n<p><strong>Little value<\/strong> in the treatment of acute myeloid leukemia. While they have been included in some combination chemotherapies, their importance in such regimens is unclear <\/p>\n\n\n\n<p><strong>Chronic\nLymphocytic Leukemia<\/strong><\/p>\n\n\n\n<p>Corticosteroids\nare particularly useful if the neoplasm is associated with autoimmune hemolytic\nanemia, neutropenia, and thrombocytopenia with hemorrhagic complications. Glucocorticoids\nalleviate the lymphadenopathy and hepatosplenomegaly that are often associated\nwith this condition.<\/p>\n\n\n\n<p><strong>Chronic\nMyeloid Leukemia<\/strong><\/p>\n\n\n\n<p>Chronic\nmyeloid leukemia (CML) in the chronic phase presents no indication for\ncorticosteroids. <\/p>\n\n\n\n<p><strong>Hodgkin\nLymphoma<\/strong><\/p>\n\n\n\n<p>Hodgkin\nlymphoma is a solid tumor that is now considered curable by chemotherapy. <\/p>\n\n\n\n<p>Corticosteroids\nalone can achieve worthwhile objective results in 66% of Hodgkin lymphoma\npatients resistant to alkylating agents. <\/p>\n\n\n\n<p><strong>Non-Hodgkin\nLymphoma<\/strong><\/p>\n\n\n\n<p>Corticosteroids\nused as single-agent therapy produce temporary responses in patients with\nnon-Hodgkin lymphoma; they are therefore included in virtually every complex\nregimen used for the treatment of non-Hodgkin lymphoma. <\/p>\n\n\n\n<p>Patients with\ndisseminated lymphomas \u00e0\nintensified CHOP regimen&nbsp;<\/p>\n\n\n\n<p>One study\nindicates that the use of interferon-\u03b12b in combination with a typical\nglucocorticoid-containing drug regimen produces good results (85% overall\nresponse rate and 86% 3-year survival rate).&nbsp;For tumors within the central\nnervous system, dexamethasone is preferred instead of prednisone to decrease\ntumor swelling.<\/p>\n\n\n\n<p><strong>Multiple\nMyeloma<\/strong><\/p>\n\n\n\n<p>The standard therapy for multiple myeloma, melphalan, and prednisone, results in a 50% response rate. Complete remission is rare, however, and the median survival is only 24 to 30 months. A combination of vincristine, Adriamycin, and dexamethasone (VAD) is also effective, especially in refractory disease.<\/p>\n\n\n\n<p>The use of interferon-\u03b1 along with a glucocorticoid for maintenance therapy appears to prolong remission duration.\u00a0Thalidomide produces a response in about 30% of patients with refractory disease and is being investigated in combination with dexamethasone as initial therapy. <\/p>\n\n\n\n<p><strong>Breast\nCancer<\/strong><\/p>\n\n\n\n<p>Although\nnever used as the sole treatment for breast cancer, glucocorticoids are\nincluded in various combination chemotherapies. Cyclophosphamide, methotrexate,\nand 5-fluorouracil (CMF)-type regimens, with and without prednisone, resulting\nin tumor regression in 50 to 80% of patients and complete response in 15 to\n20%.<\/p>\n\n\n\n<p>For\nmetastatic breast cancer patients who do not consent to aggressive cytotoxic\nchemotherapy, the alternative combination of mitoxantrone, leucovorin,\n5-fluorouracil, and prednisone induced tumor regression in 67% of patients with\na complete response in 25%.<\/p>\n\n\n\n<p><strong>Other\nUses<\/strong><\/p>\n\n\n\n<p>Hydrocortisone\nreplacement (approximately 40 mg\/d) is indicated after surgical or medical (via\nsteroid synthesis inhibitors) adrenalectomy. <\/p>\n\n\n\n<p>Such\nadrenalectomy eliminates circulating steroids in cases of breast cancer,\nprostate cancer, and ectopic ACTH excess.&nbsp;Hemangiomas in infants are often\ntreated with injections of glucocorticoids. Thymomas are often treated with\nglucocorticoids either alone or in combination with cytotoxic drugs.&nbsp;Other\ntumors that have been treated with combination chemotherapy involving a\nglucocorticoid include medulloblastoma, primitive neuroectodermal tumors, and\nependymomas. <\/p>\n\n\n\n<p><strong>Symptomatic Uses of Corticosteroids<\/strong><\/p>\n\n\n\n<p><strong>Palliative\nCare<\/strong><\/p>\n\n\n\n<ul><li>Glucocorticoid\ntreatment produces rapid symptomatic improvements in critically ill patients,\nincluding relief of fever, sweats, lethargy, weakness, and other nonspecific\neffects of cancer.<\/li><li>&nbsp;Glucocorticoids also cause mild euphoria, a\ngeneral feeling of well being, and stimulation of appetite.&nbsp;<\/li><li>These\neffects are transient, and only short-term treatment is possible due to the side\neffects of the high doses. In addition, glucocorticoid withdrawal can result in\nadrenocortical insufficiency. <\/li><li>For\nthese reasons, corticosteroid treatment is appropriate only for patients whose\nlife expectancy is brief (a few weeks or less). <\/li><li>Although\ndoses of 25 mg\/d prednisolone can be used, with a decrease to 7.5 to 15 mg\/d\nfor maintenance of effects, other options for pain management in terminally ill\npatients make the use of glucocorticoids in this context relatively rare.<\/li><\/ul>\n\n\n\n<p><strong>Hypercalcemia<\/strong><\/p>\n\n\n\n<p>Hypercalcemia,\na common complication of many malignancies,&nbsp;is often caused by increased\nbone resorption and renal calcium reabsorption. <\/p>\n\n\n\n<p>This effect\nis thought to be a consequence of factors secreted by tumors, particularly\ntumors of lymphoid origin. <\/p>\n\n\n\n<p>Although\nglucocorticoids do not lower normal calcium levels, high-dose glucocorticoid\nhas efficacy in the treatment of hypercalcemia (100 mg\/d prednisolone, 400 mg\/d\nhydrocortisone). <\/p>\n\n\n\n<p>Glucocorticoids\nare most effective on hypercalcemia that is secondary to high vitamin D levels,\nand least effective in patients with solid tumors. Results in the treatment of\nmultiple myeloma patients are inconsistent. Therefore, glucocorticoids are a poor\ntreatment modality except in cases of vitamin D-mediated hypercalcemia.<\/p>\n\n\n\n<p><strong>Central\nNervous System Tumors<\/strong><\/p>\n\n\n\n<p>Neurologic\nsymptoms from primary and metastatic brain and spinal cord tumors are partially\ncaused by peritumoral edema.<\/p>\n\n\n\n<p>Glucocorticoids\ncan ameliorate these symptoms in approximately 70 to 80% of cases after several\ndays of treatment,&nbsp;likely by inducing both decreased edema production and\nincreased edema reabsorption. <\/p>\n\n\n\n<p>Dexamethasone\nis the recommended steroid for this treatment because it contains no\nmineralocorticoid activity and is highly potent. A dose of 16 mg\/d is used with\nan increase to 100 mg\/d if no response occurs. <\/p>\n\n\n\n<p>This dose is\ncontinued until the maximum response is obtained, then decreased gradually and\nmaintained at the lowest effective dose. <\/p>\n\n\n\n<p><strong>Antiemetic\nAction<\/strong><\/p>\n\n\n\n<p>Glucocorticoids\ndecrease the severity of chemotherapy-induced emesis.&nbsp;Both\ndexamethasone (8 to 20 mg) and methylprednisolone (125 to 250 mg) are employed\nfor this indication, with vomiting episodes reduced by as much as 74%.<\/p>\n\n\n\n<p><strong>Glucocorticoids are most effective when used at low doses\nto enhance the antiemetic efficacy of other drugs. <\/strong><\/p>\n\n\n\n<p>Recent\nfindings suggest that the combination of glucocorticoids with serotonin\nreceptor antagonists (eg, ondansetron, granisetron, tropisetron) is extremely\neffective.<\/p>\n\n\n\n<p>The mechanism\nof glucocorticoid-mediated antiemesis is unknown. The effect may be associated\nwith decreases in prostaglandin synthesis, or glucocorticoids may act directly\non the chemoreceptor trigger zone by modifying capillary permeability or\nstabilizing lysosomal membranes.<\/p>\n\n\n\n<p><strong>Dyspnea\nCaused by Lymphangitic Carcinomatosis<\/strong><\/p>\n\n\n\n<p>Dyspnea in\nlymphangitic carcinomatosis may be a result of tumor edema and is effectively\nrelieved in most cases, at least temporarily, by glucocorticoid treatment.<\/p>\n\n\n\n<p>Prednisone is\ngiven at a dose of 60 to 100 mg\/d and then reduced rapidly to the minimum level\nthat maintains a response. If the primary tumor is chemosensitive, then\ncytotoxic agents are also given.<\/p>\n\n\n\n<p><strong>Other\nUses of Glucocorticoids<\/strong><\/p>\n\n\n\n<ul><li>Acute upper airway obstruction can result from direct tumor growth or by compression from thyroid, lung, and esophageal cancers. This obstruction can be reduced by glucocorticoid treatment, either alone or in combination with radiotherapy.<\/li><li>Other cancer-related obstructions and mass effects, including superior vena cava syndrome; lymphedema; liver metastases; masses in the pelvis, mediastinum, or retroperitoneum; and blockages of the large bowel or ureter,\u00a0can be partially controlled by glucocorticoids. <\/li><li><strong>Therapeutic effects are a result of a reduction in peritumoral inflammation and edema. Pain from bone metastases or metastatic arthralgia from solid tumors often responds to glucocorticoid treatment.<\/strong><\/li><li>Several chemotherapeutic agents (mitomycin, bleomycin, busulfan, carmustine), as well as radiotherapy, are associated with pulmonary toxicity. Preventive glucocorticoid administration during chemotherapy, for example, dexamethasone administration during mitomycin chemotherapy for nonsmall-cell lung cancer,\u00a0can prevent lung injury. However, decreased antineoplastic effects of mitomycin in such a context suggests that further study of this application is warranted. <\/li><li>Loss of vision associated with pseudotumor cerebri can be treated with glucocorticoids. <\/li><\/ul>\n","protected":false},"excerpt":{"rendered":"<p>Corticosteroids in the Treatment of Neoplasms Mechanism of Glucocorticoid Action The majority of the biologic effects of steroid hormones are mediated by intracellular receptors specific for each class of steroid. The glucocorticoid receptor (GR), a cytoplasmic protein, is present in all tissues that are targets of glucocorticoid action. Activation of GR \u00e0 involve a conformational[&#8230;]\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_seopress_robots_primary_cat":"","_seopress_titles_title":"","_seopress_titles_desc":"","_seopress_robots_index":"","footnotes":""},"categories":[3],"tags":[],"_links":{"self":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/284"}],"collection":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/comments?post=284"}],"version-history":[{"count":0,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/284\/revisions"}],"wp:attachment":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/media?parent=284"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/categories?post=284"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/tags?post=284"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}