Low doses of oral dexamethasone for hormone-refractory prostate carcinoma

Nishimura, Kazuo; Nonomura, Norio; Yasunaga, Yutaka; Takaha, Natsuki; Inoue, Hitoshi; Sugao, Hideki; Yamaguchi, Seiji; Ukimura, O; Miki, Tsuneharu; Okuyama, Äkïhïko

doi:10.1002/1097-0142(20001215)89:12<2570::aid-cncr9>3.0.co;2-h

Cited by 116 publications

(83 citation statements)

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“…Responses have been seen to steroids and estrogens (Farrugia et al, 2000;Nishimura et al, 2000), and chemotherapy has shown a survival advantage for these patients (Petrylak et al, 2004;Tannock et al, 2004). Until recently, it has been a universal practice to continue androgen deprivation during chemotherapy, despite previous progression on this treatment.…”

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confidence: 99%

A phase II study investigating the re-induction of endocrine sensitivity following chemotherapy in androgen-independent prostate cancer

et al. 2008

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When chemotherapy is used in androgen-independent prostate cancer (AIPC), androgen deprivation is continued despite its failure. In this study, we investigated whether it was possible to re-induce hormone sensitivity in previously castrate patients by stopping endocrine therapy during chemotherapy. A phase II prospective study investigated the effects of reintroduction of endocrine therapy after oral chemotherapy in 56 patients with AIPC, which was given without concurrent androgen deprivation. After chemotherapy, patients were given maximum androgen blockade until failure when treatment was switched to diethylstilbestrol and dexamethasone. Patients had already received these endocrine treatments in the same sequence before chemotherapy. All patients were castrate at the start of chemotherapy. Forty-three subsequently restarted endocrine therapy after the completion of chemotherapy. The median overall survival for these 43 patients from the time of restarting endocrine therapy was 7.7 months (95% confidence interval (CI): 3.7 -10.9 months). Sixteen (37%) patients had a 50% PSA response to treatment, which was associated with improved overall survival (14.0 months vs 3.7 months P ¼ 0.003). Eight out of 12 patients who did not respond to diethylstilbestrol before chemotherapy did so post chemotherapy. Re-induction of hormone sensitivity can occur after chemotherapy in AIPC.

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confidence: 99%

A phase II study investigating the re-induction of endocrine sensitivity following chemotherapy in androgen-independent prostate cancer

et al. 2008

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“…In previously reported outcomes of glucocorticoids for AIPC (3,11), the PSA response rate (≥50% decrease in PSA) ranged from 44 to 68%, and the median time to progression was approximately 9 months. our results were comparable to these findings.…”

Section: Discussionmentioning

confidence: 94%

“…Il-6 is known to be suppressed by glucocorticoids (6) and to stimulate the growth of prostate cancer cell lines through glucocorticoid receptors in an androgen-independent manner (3,(14)(15)(16)(17). In addition, Il-6 has been shown to activate the androgen receptor through a stAt3-dependent pathway (17)(18)(19).…”

Section: Discussionmentioning

confidence: 99%

“…In addition to their anti-inflammatory effects, these agents exhibit antitumor activity. However, their therapeutic role in AIPc remains unclear (2,3). A few studies have demonstrated negative effects for prostate cancer suppression with higher doses of DXM (4,5), or the antagonistic activity of DXM on prostate cancer cells with specific androgen receptor mutation (6).…”

Section: Introductionmentioning

confidence: 99%

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Oral low-dose dexamethasone for androgen-independent prostate cancer patients

Komiya¹,

Shimbo²,

Suzuki³

et al. 2010

Oncology Letters

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Abstract. We retrospectively evaluated the outcome of oral low-dose dexamethasone (DXM) therapy for androgenindependent prostate cancer (AIPc). Between January 1999 and April 2006, 99 consecutive patients with AIPc were enrolled in this study. the median patient age was 70 years (range 46-86), and the median pretreatment prostate-specific antigen (PsA) level was 243 ng/ml (range 8.2-29600). Median follow-up was 41.9 months (range 11.4-170.4). Upon biochemical failure, patients were treated with oral low-dose DXM. A total of 40 of the 99 cases (40.4%) showed a ≥50% decrease in serum PSA levels (PSA responders). Twenty-five cases (25.2%) showed a <50% decrease in PSA, and the remaining 34 cases (34.3%) had increased PsA levels (PsA non-responders). the median PsA progression-free survival was 3.0 (range 0-27) and 8.0 months (range 2-27) for the entire cohort and PsA responders, respectively. the PsA responders had a significantly increased survival (median 30.1 months) compared to the non-responders (median 8.8 months, P<0.001). of the 34 patients who were under pain control for bone metastases before the administration of DXM, 23 (67.6%) were able to discontinue the regular use of analgesics. the PsA responders also showed an increase in hemoglobin levels. the change in serum interleukin-6 levels was significantly associated with a response to DXM (P=0.0065). Severe adverse events of DXM were rare. clinicopathological factors predicting the PsA response to DXM were age, time from initial androgen deprivation therapy to DXM and PsA velocity prior to DXM. In conclusion, oral low-dose DXM led to an acceptable PsA response in patients with AIPc. thus, this therapy may be an effective and safe alternative for the treatment of AIPc, particularly for patients who are not favourable candidates for chemotherapy.

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“…28 Higher PSA response rates have been described with dexamethasone, a more potent glucocorticoid. 29 Glucocorticoids have been used in a number of randomized multicenter trials and have a well defined side effect profile, including glucose intolerance, redistribution of body fat, easy bruising, and steroid myopathies. Care should be taken before abruptly discontinuing glucocorticoids because an Addisonian crisis may occur.…”

Section: Hormonal Manipulation: Second-line Hormonal Agentsmentioning

confidence: 99%