FWIW : Doc Says That Corticosteroids Are Detrimental

[Bill]

FWIW : When my wife was d/c'd from the hospital she was d/c'd with several Rxs including prednisone 40mg. daily. This was ordered by an internist. She saw her med onc two days later. He had a fit when he discovered this Rx and immediately had my wife weened off of prednisone over the next 5 days. He states that corticosteroids are detrimental to her lung cancer condition and should be used only for acute care. He states that long-term use can lead to increased pulmonary congestion in lung cancer patients. I've always been an advocate of corticosteroid use in pulmonary disease, generally speaking, so this precaution was news to me. No details provided by him. I didn't ask as I expected my wife to be weened off of the prednisone anyway.

[Fay A.]

Bill,

My docs (Med Oncs at several cancer centers) did not want me to take steroids for any reason other than a serious and acute event (or during CT scans with IV contrast due to allergic response) because it suppresses the immune system. I had measurable malignant disease, and any additional suppression of my immune system was not wanted.

ADDENDUM:

PS Forgot about the doses during chemo with Taxotere and Carboplatin. I guess the Taxanes are notorious for producing allergic responses in almost everyone, so I did receive steroids during that time.

[SDianneB]

Glad you brought this up. I had small doses of steroids as part of the pre-meds when I had chemo, but that was it -- no Rx, no ongoing dose, nothing. When I had the PCI, the radiation oncologist very strongly recommended to me that I not take steroids unless the side effects of PCI were worse than they would be from the steroids. Since I had virtually no side effects from the PCI, I never needed the steroids.

Every doctor I've seen so far is very cautious about giving steroids. I asked once about steroids because so many people seemed to be taking them, and was basically told "consider yourself lucky that you don't need them."

Many years ago I had Bell's palsy, and part of the treatment for that was steroids for about 2 weeks or so. It started out with the largest dose, then tapered off until the end of the Rx. I had the swollen face, appetite that would stop, etc. But along with the other treatment (PT, B-12 injections daily) it took care of the Bell's palsy.

Since the cancer diagnosis, the only steroids I've had were the 4 pre-med doses. Guess I should consider myself lucky.

Di

[Pamela]

Bill, hang on to that doctor. It's wonderful that he noticed it and took action. The doctor who prescribed it likely wouldn't have followed up. Too often a patient is given a prescription with NO information on side effects, possible adverse reactions, etc., and it can cause very, very serious problems. If you have the problems he described with prednisone, imagine the damage that can be done with Decadron.

Pam

[john]

I have always wondered about this. Steroids can be immunosuppressive. Some of them can lower your immunity.

On the other hand, I have read that some steroids when used in combo with chemo actually increase the effectiveness of the chemo.

So - I guess the bottom line is listen to the Docs.

[Addie]

Here's a FWIW for you all....

I've been on prednisone for a year and a half...due to Polymyalgia Rheumatica....sort of "arthritis of the muscles". Never was on a high dose...started at 10 mgs. and am down to 4 mgs. daily now.

I've been told it's possible that chemo will cure my symptoms...so that I no longer need to take the pred. But at this point, I've just slooooowly been reducing my dosage. Nothing drastic...which is how you need to deal with steroids anyway.

I don't take my daily 4 mgs. on chemo days...because on those days I'm getting 8 mgs. of Decadron.

I like what you said, John....that in some cases steroids will actually increase the effectiveness of chemo. I had an outstanding result from three cycles of Topotecan recently. Cleaned out my pancreas totally and the liver tumors are mostly 50% reduced!!!

Did the prednisone help?? Sure hasn't seem to hurt. I think I might stay at this dosage, with my docs' approval, till the next three cycles of chemo are done!

[john]

Addie,

I can not find the article about steroids and chemo that seemed to increase effectiveness but here is a newer study that says steroids *MAY* DECREASE the effectiveness of chemo.

This study is only in the lab and not humans so it may not be valid as far as chemo in LC patients goes

I found another study that raises concerns about steroids and chemo

I wanted to do a search again to make sure my previous post was accurate as far as the steroids and chemo. I will try to find the other article

John

Br J Cancer. 2005 Mar 28;92(6):1084-8. Related Articles, Links

Dexamethasone-induced cisplatin and gemcitabine resistance in lung carcinoma samples treated ex vivo.

Gassler N, Zhang C, Wenger T, Schnabel PA, Dienemann H, Debatin KM, Mattern J, Herr I.

Department of Pathology, University of Heidelberg, Germany.

Chemotherapy for lung cancer not only has severe side effects but frequently also exhibits limited, if any clinical effectiveness. Dexamethasone (DEX) and similar glucocorticoids (GCs) such as prednisone are often used in the clinical setting, for example, as cotreatment to prevent nausea and other symptoms. Clinical trials evaluating the impact of GCs on tumour control and patient survival of lung carcinoma have never been performed. Therefore, we isolated cancer cells from resected lung tumour specimens and treated them with cisplatin in the presence or absence of DEX. Cell number of viable and dead cells was evaluated by trypan blue exclusion and viability was measured by the MTT-assay. We found that DEX induced resistance toward cisplatin in all of 10 examined tumour samples. Similar results were found using gemcitabine as cytotoxic drug. Survival of drug-treated lung carcinoma cells in the presence of DEX was longlasting as examined 2 and 3 weeks after cisplatin treatment of a lung carcinoma cell line. These data corroborate recent in vitro and in vivo xenograft findings and rise additional concerns about the widespread combined use of DEX with antineoplastic drugs in the clinical management of patients with lung cancer.

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Cancer Res. 2003 Jun 15;63(12):3112-20. Related Articles, Links

Glucocorticoid cotreatment induces apoptosis resistance toward cancer therapy in carcinomas.

Herr I, Ucur E, Herzer K, Okouoyo S, Ridder R, Krammer PH, von Knebel Doeberitz M, Debatin KM.

Division of Molecular Oncology/Pediatrics, German Cancer Research Center, 69120 Heidelberg, Germany. i.herr@dkfz.de

Chemotherapy and radiation therapy for cancer often have severe side effects that limit their efficacy. Glucocorticoids (GCs) are frequently used as cotreatment because they may have potent proapoptotic properties and reduce nausea, hyperemesis, and acute toxicity on normal tissue. In contrast to the proapoptotic effect of GCs in lymphoid cells, resistance toward cancer therapy-mediated apoptosis was induced in solid tumors of human cervix and lung carcinomas. Filter hybridization, expression data, as well as functional assays identified multiple core apoptosis molecules, which are regulated by GCs in a pro- or antiapoptotic manner. Both antiapoptotic genes such as FLIP and members of the Bcl-2 and IAP family as well as proapoptotic elements of the death receptor and mitochondrial apoptosis pathways were down-regulated in carcinomas resulting in a decreased activity of caspase-8, caspase-9, and caspase-3. In contrast, death receptor and mitochondrial apoptosis signaling as well as caspase activity was enhanced by dexamethasone in lymphoid cells. To restore apoptosis sensitivity in dexamethasone-treated carcinomas, caspase-8 and caspase-9 were transfected. This resensitized tumor cells in vitro and xenografts in vivo to cisplatin induced cell death. These data therefore raise concern about the widespread combined use of GCs with antineoplastic drugs or agents in the clinical management of cancer patients.

[john]

One that says DEX and chemo increase effectiveness

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Clin Cancer Res. 2004 Mar 1;10(5):1633-44. Related Articles, Links

Pretreatment with dexamethasone increases antitumor activity of carboplatin and gemcitabine in mice bearing human cancer xenografts: in vivo activity, pharmacokinetics, and clinical implications for cancer chemotherapy.

Wang H, Li M, Rinehart JJ, Zhang R.

Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.

PURPOSE: The present study was undertaken to determine the effects of dexamethasone (DEX) pretreatment on antitumor activity and pharmacokinetics of the cancer chemotherapeutic agents carboplatin and gemcitabine. EXPERIMENTAL DESIGN: Antitumor activities of carboplatin and gemcitabine with or without DEX pretreatment were determined in six murine-human cancer xenograft models, including cancers of colon (LS174T), lung (A549 and H1299), and breast (MCF-7 and MDA-MB-468) and glioma (U87-MG). Effects of DEX on plasma and tissue pharmacokinetics of carboplatin and gemcitabine were also determined by using the LS174T, A549, and H1299 models. RESULTS: Although DEX alone showed minimal antitumor activity, DEX pretreatment significantly increased the efficacy of carboplatin, gemcitabine, or a combination of both drugs by 2-4-fold in all xenograft models tested. Without DEX treatment, the tumor exposure to carboplatin, measured by the area under the curve, was markedly lower than normal tissues. However, DEX pretreatment significantly increased tumor carboplatin levels, including 200% increase in area under the curve, 100% increase in maximum concentration, and 160% decrease in clearance. DEX pretreatment similarly increased gemcitabine uptake in tumors. CONCLUSIONS: To our knowledge, this is the first report that DEX significantly enhances the antitumor activity of carboplatin and gemcitabine and increases their accumulation in tumors. These results provide a basis for further evaluation of DEX as a chemosensitizer in patients.

[paddy]

Thank You Bill for bringing this to our attention. Paddy