Why are glucocorticoids used with cancer patients

If survival graphs were not provided, exponential survival was assumed and the median survival was used to generate survival data. Odds ratio estimates and between-group comparisons for the combined trials were made using the Mantel-Haenszel fixed effect model.

A result had to have a p value of less than 0. The literature was searched for clinical studies of glucocorticoids. Studies were eligible if patients had nonhematologic malignancy, and if there were endpoints of tumor response or tumor control or survival. For RCTs and meta-analyses, trials comparing two glucocorticoid arms or a glucocorticoid arm to a nonglucocorticoid arm were eligible.

After excluding duplicate publications of the same trial, fifty four RCTs met the eligibility criteria [ 5 — 54 ] and [ 55 — 61 ] ; one meta-analysis met the eligibility criteria [ 62 ]. In nonhematologic malignancy other than breast cancer or prostate cancer or thymoma, four case series of glucocorticoid monotherapy with tumor response data were identified [ 67 — 70 ]. One of the case series is a clinical trial; however, tumor response rate was not a preplanned endpoint, so it is presented as a case series [ 67 ].

Three clinical trials, with no available results, were identified [ 71 — 73 ]. Nine case reports of glucocorticoid monotherapy, other than breast cancer or prostate cancer or thymoma regressing in response to glucocorticoid monotherapy, were found [ 74 — 83 ].

No article was excluded due to quality. Glucocorticoids are commonly given as premedication with chemotherapy to prevent nausea and vomiting. In the chemotherapy trials mentioned in this review, there are two trials where it is clear whether glucocorticoids were used as premedication in patients not on the glucocorticoid arm [ 23 , 28 ]. In the other chemotherapy trials, there is no mention of whether such usage was permitted or not. There are case reports of nonhematologic malignancy either regressing or having increased growth in response to glucocorticoids.

It is reasonably well documented in the literature that thymoma can sometimes respond to glucocorticoids [ 84 ]. In melanoma, 2 doses of mg of intravenous hydrocortisone 8 hours apart caused tumor lysis syndrome in a patient with melanoma [ 74 ]. There are case reports where glucocorticoids apparently stimulated the growth of melanoma [ 75 , 76 ].

There is a case report of liver metastasis of thymic carcinoid responding to prednisolone [ 77 ]. Metastatic renal cell carcinoma might have shown a complete response to glucocorticoids in two patients[ 78 , 79 ]. There are case reports where glucocorticoids apparently stimulated the growth of breast cancers [ 80 — 83 ]. The four case series of glucocorticoid monotherapy are shown in Table 1 [ 67 — 70 ]. They included patients with a variety of cancers, such as lung cancer, GI cancer, breast cancer and sarcoma.

No tumor regression, objective improvement or relief of pain was noted. Glucocorticoid doses were not dissimilar taking into account relative glucocorticoid activities Table 2. For any particular tumor type, the number of cases is small: the one exception is the lung cancer patients in the case series of de Camp [ 69 ]. With regards to quality, two case series were from tertiary care centers; the two that were not originated from secondary care institutions [ 67 , 69 ].

Three of the four case series had less than 50 patients [ 67 , 68 , 70 ]. None of the case series were multi-institutional. Three of the four case series did not describe eligibility criteria [ 68 — 70 ]. In one case series, patients were similar with regards to the state of cancer progression; in the other studies, not enough information was provided to assess similarity [ 67 ].

In one case series, followup was long enough to assess whether glucocorticoids could cause cancer to decrease in size; in the other studies, it was unclear if followup was sufficient to assess this [ 70 ]. In none of the case series was reduction in tumor size assessed using objective criteria. In the largest trial patients , 13 of the 24 responses were in breast and prostate cancer with the 2 complete responses being in breast and prostate cancer [ 66 ].

The next largest trial was 94 patients with no responses [ 63 ]. The two glucocorticoids used in these clinical trials were fluorometholone and NSC Fluorometholone may have progestational properties [ 22 ].

One hundred mg of NSC is equivalent to 50—67 mg of prednisone; however, it also has sex steroid properties. With regards to quality, all the clinical trials were from tertiary care centers. All clinical trials had more than 50 patients. Three of the four trials were multi-institutional [ 63 , 65 , 66 ]. One of the trials did not describe eligibility criteria [ 65 ].

In one trial, patients were similar with regards to the state of cancer progression; in the other trials, not enough information was provided to assess similarity [ 64 ]. In two trials, followup was long enough to assess whether glucocorticoids could cause cancer to regress in size; in the other two trials, it was unclear if followup was sufficient to assess this [ 64 , 66 ].

Reduction in tumor size was assessed using objective criteria in three of the studies [ 64 — 66 ]; this was unclear in the other study.

There are two types of trials in this category. In the first type, glucocorticoids are given as monotherapy and compared to other endocrine therapies given as monotherapy. There are ten trials of this type, which tend to be small and often use endocrine therapies that are no longer given. In these trials, the vast majority of patients were postmenopausal or enrolment was limited to postmenopausal patients. The results show that glucocorticoids have modest activity in postmenopausal women.

A description of these trials is given in Table 4 [ 5 , 15 , 18 , 19 , 22 , 38 , 47 , 55 , 56 ]. The three earliest trials used response criteria that are not readily comparable to presently used response criteria [ 5 , 19 , 22 ]. These trials tend to be larger, more recent and limited to women who are postmenopausal or who received ovarian irradiation. Results are presented in Table 4 [ 7 , 24 , 37 , 46 ].

As these trials were more similar in nature, meta-analyses of response rates and survival were undertaken. As seen in Figure 1 , the addition of glucocorticoids to another endocrine therapy resulted in an increased response rate. Figure 2 shows that this addition does not change one year survival rates.

However, there was evidence for a lack of homogeneity among the four studies in Figure 2 , as shown by the chi-square test and its p value. The meta-analysis was repeated, except that the trial which was furthest from the other three trials in response rate and survival was omitted [ 24 ].

The result of the omission was that the addition of glucocorticoids did not change one year survival rates, although the lack of homogeneity disappeared odds ratio of 0.

This is consistent with the results from the advanced breast cancer setting. In the first of the two trials of glucocorticoid monotherapy, glucocorticoids weren't beneficial in the postmenopausal group; they might have been beneficial in the premenopausal group, who were treated with ovarian irradiation [ 44 ]. In the second trial of glucocorticoid monotherapy, premenopausal women were randomly treated with chemotherapy or ovarian ablation followed by a second randomization to glucocorticoids versus no glucocorticoids.

Regardless of whether a woman received chemotherapy or ovarian ablation, glucocorticoids were not beneficial. One feature that complicates interpretation of the second trial is that glucocorticoids were started at the time of oophorectomy or at the start of chemotherapy, and were to be given for 5 years unless relapse occurred. Those in the chemotherapy arm got glucocorticoids during their 24 weeks of chemotherapy.

Glucocorticoid administration resulted in less bone marrow suppression during chemotherapy [ 13 ]. Decreased thrombocytopenia [ 21 , 40 ] and increased administered chemotherapy dose [ 21 , 40 , 48 ] were associated with glucocorticoid administration in several of these trials. In six of these trials, response rates are given; in four of these trials, survival data is given.

It was felt that there was enough similarity in these trials to perform meta-analyses. Meta-analyses of response rates and survival are presented in Figures 3 and 4 respectively.

The addition of glucocorticoids to chemotherapy in the advanced breast cancer setting resulted in an increased response rate.

However, there was no effect on one year survival. There are two trials in this category. This is consistent with what has been found in the advanced breast cancer setting.

At the time of enrolment, none of the participants were postmenopausal. In comparison to trials that enroll postmenopausal women, this might lessen the possible impact of glucocorticoids as endocrine therapy. However, many women on these trials subsequently developed amenorrhea.

A description of these trials is given in Table 7 [ 12 , 53 , 85 ]. In one of the trials, there was a significant increase in bone, alone or in combination with other sites, as the site of first relapse in the chemotherapy plus prednisone arm relative risk of 2.

The authors postulated that the increased rate of bone metastases as a first relapse site in this arm might be due to cytokine inhibition, which might reduce a putative anti-cancer process in bone, or to increased bone absorption [ 53 ]. In prostate cancer, there are two RCTs of glucocorticoids in untreated patients [ 43 , 59 ]. Both are trials of orchiectomy versus orchiectomy plus glucocorticoids versus orchiectomy plus cyproterone acetate.

The small numbers enrolled preclude analysis, other than it is improbable that glucocorticoids worsen outcome when added to orchiectomy. Both trials used response criteria that are not readily comparable to presently used response criteria. There are five randomized controlled trials of glucocorticoids in patients with hormone refractory prostate cancer [ 8 , 32 , 33 , 35 , 36 , 54 , 60 ]. These are all trials comparing glucocorticoid monotherapy to other monotherapies.

When glucorticoids are compared to other hormonal therapies progestational agents and flutamide , little difference was noted. When glucocorticoids were compared to liarozole a retinoic acid stimulating agent , glucocorticoids resulted in a better outcome. In the three oldest trials, the response criteria used are not readily comparable to presently used response criteria [ 8 , 33 , 35 ]. This small trial has been published in abstract form only; it is difficult to draw conclusions based on the information presented.

See Table 8 for a description of these trials. There is one trial comparing glucocorticoid monotherapy to placebo in GI cancer; no difference in survival was found [ 26 ]. One of the two trials used response criteria that are not readily comparable to those presently used. The chemoprotective property of dexamethasone, allowing a greater FUDR dose, may have contributed to the improved results in the combined arm [ 11 ].

Other postulated reasons are a potentiation of FUDR cytotoxicity by dexamethasone and a potential antiangiogenic property of dexamethasone [ 86 , 87 ]. There are two trials of preoperative glucocorticoids in patients scheduled to undergo esophagectomy; there was no effect on survival [ 51 , 58 ]. A description of the GI trials is given in Table 9.

This trial uses a higher dose of glucocorticoids than any other trial described in this review; however, administration was on an intermittent, rather than a continuous, basis.

The addition of methylprednisolone to BCNU had a neutral effect on survival. Infection was significantly greater in the BCNU plus methylprednisolone arm than the other arms; information on the type and severity of infection is not available. There are five randomized controlled trials of glucocorticoid monotherapy in patients with a variety of cancers; these trials are dissimilar in nature. The first two trials used glucocorticoid doses higher than any other trial in this review, with the exception of the previously mentioned randomized controlled trial in CNS neoplasms.

However, glucocorticoid administration was continuous in these two trials. If these drugs are suddenly stopped, you not only are not getting the prescription, but it can take a significant amount of time before your body realizes that it needs to make its own corticosteroids again. Short-term side effects side effects which occur early or when steroids are used for only a short period of time include:.

Long-term side effects of steroids are common and may include:. Some side effects may be good or bad depending on a person's clinical situation. For example, increased appetite and weight gain may be beneficial in underweight people with cancer. Taking your medication with food can help with some of the problems that steroids can cause to your digestive tract. You may also choose to take these types of medications early on in the day so that they are less likely to impact your sleep at night.

As with many medication side effects, your oncologist, nurse, or pharmacist can often provide you with strategies to help control or minimize them. While you may have heard the expression "roid rage," which is used to describe angry behaviors and outbursts of individuals who take anabolic steroids, it's important to note that corticosteroids can also have serious effects on mood.

The psychological side effects of corticosteroids can range from irritability, restlessness, and anger all the way to paranoia, confusion, and mania.

Conversely, it is not uncommon to have a low mood or even depression after you discontinue these medications. Unfortunately, with all that is going on in your life with cancer, it may be difficult to determine the source of these feelings.

Yes, you are on steroids, but you are also getting treated for cancer and trying to carry on a somewhat normal life. It's normal to experience a wide range of emotions when coping with cancer. A general rule of thumb is that if your mood changes are impacting your quality of life or the health of your relationships, you should talk to your oncology team. If your feelings are severe, you may need to seek immediate assistance. As with most cancer treatment medications, it is very important to take steroids exactly as your healthcare provider describes.

Here are some good questions to ask your healthcare team about your steroids before you start:. As noted earlier, taking steroid medications has an impact on how much natural steroid your body produces. For this reason, when your steroids are no longer needed as part of your therapy, your healthcare provider will often taper the dose off instead of stopping them abruptly. It is extremely important that you do not stop taking this medication unless you are told to by your healthcare provider.

In rare instances, stopping steroids abruptly can result in life-threatening adrenal crisis. Even if you are following a tapering schedule, let your healthcare provider know if your symptoms become bothersome. Some people have to be tapered off of these medications very slowly over a period of weeks or even months. Steroids in some ways might be thought of as the unsung heroes of cancer care.

While chemotherapy, radiation therapy, and especially the newer targeted therapies and immunotherapy get all the praise for killing cancer, steroids work quietly behind the scenes, preventing and minimizing complications and even making other therapies work better. That is why they play a big role in the treatment of both blood-related cancers and solid tumors.

That said, these drugs do have a significant number of short and long-term side effects, some of which can be serious. Liquid pred and meticorten and orasone are other names for prednisone. In some cases, health care professionals may use the trade name deltasone or other names liquid pred or meticorten or orasone when referring to the generic drug name prednisone.

Drug type: Prednisone has many uses in the treatment of cancer. It is classified as a glucocorticosteroid. For more detail, see "How this drug works" section below.

Note: If a drug has been approved for one use, physicians sometimes elect to use this same drug for other problems if they believe it might be helpful. This list includes common and less common side effects for individuals taking prednisone. However, you should always inform your health care provider if you experience any unusual symptoms.

Contact your health care provider immediately , day or night, if you should experience any of the following symptoms :. In breast cancer, the estrogen receptor ER drives cell growth, proliferation, and metastasis, and the androgen receptor AR plays a similar role in prostate cancer. Accordingly, treatment of these diseases has focused on blocking steroid hormone receptor function.