Oestrogen Therapy and Serum Cortisol in Carcinoma of the Prostate

Morales, Álvaro; Kraus, Arthur S.; Bruce, Andrew W.

doi:10.1111/j.1464-410x.1975.tb03966.x

Cited by 7 publications

(9 citation statements)

References 27 publications

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“…Most of those studies, however, did not use TTh alone. The present author and colleagues reported long ago [14] on a group of men with metastatic PCa primed with testosterone before receiving i.v. radioactive phosphorus.…”

Section: Discussionmentioning

confidence: 85%

Effect of testosterone administration to men with prostate cancer is unpredictable: a word of caution and suggestions for a registry

Morales

2011

BJU International

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What’s known on the subject? and What does the study add? Very little is known on the effect of T in men with untreated PCa. There are only two small series (including the present one) available that comprise less than 25 men with PCs receiving TTh. It raises a warning that testosterone administration to men with PCa is not always safe, that current precautions should be maintained, and that only an international registry would provide prompt answers to these issues. To assess the evidence for the concept that the androgen receptor of prostate cancer (PCa) cells becomes saturated when testosterone values exceed castrate levels, so that testosterone administration in hypogonadal men with untreated PCa does not stimulate tumour growth. To propose basic criteria for administration of testosterone to untreated patients with PCa and, as this is a rare clinical situation, to encourage the establishment of an international registry for these patients. Men with a diagnosis of PCa and symptomatic testosterone deficiency received testosterone therapy (TTh). Patients were assessed quarterly. Prostate‐specific antigen (PSA) velocity was used as the criterion to discontinue therapy and a return to nadir PSA levels allowed re‐initiation of testosterone supplementation. The responses to testosterone supplementation were varied according to each individual and were unpredictable. While some men showed little change after years of treatment, others exhibited a rapid and significant increase in PSA levels. In others, the use of intermittent therapy resulted in synchronous changes in PSA levels. Interruption of TTh invariably translated into a decrease in PSA to pre‐therapy levels. Available evidence regarding the effect of testosterone administration to hypogonadal men with untreated PCa is too limited to be considered reliable. In addition, the response to this treatment appears to be varied and unpredictable. Hypogonadism associated with untreated PCa is not common, therefore, we propose the establishment of an international registry as the quickest way to establish the basic parameters for consideration of TTh in this situation and recommendations for follow‐up. Until credible evidence becomes available, the current restrictions regarding the administration of testosterone to men with PCa should remain in place.

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Section: Discussionmentioning

confidence: 85%

Effect of testosterone administration to men with prostate cancer is unpredictable: a word of caution and suggestions for a registry

Morales

2011

BJU International

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“…Presence of complex karyotype (including 7q-, an abnormality typically associated with prior chemotherapy related leukemia/MDS) in our patient and existence of reports describing higher incidence of secondary leukemia following cisplatin and carboplatin therapy in ovarian cancer favors this conclusion [25,26]. The cause and significance of lymphopenia in majority of patients during the treatment phase is also not clear even though it has been reported in other studies evaluating estrogen, corticosteroids, suramin and mitoxantrone in HRPC [27][28][29].…”

Section: Discussionmentioning

confidence: 57%

Phase II study of oral bis (aceto) ammine dichloro (cyclohexamine) platinum (IV) (JM-216, BMS-182751) given daily x 5 in hormone refractory prostate cancer (HRPC)

et al. 2005

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JM-216 is an orally bioavailable platinum compound with activity against many tumor models. The objective of this study was to determine the safety profile and anti-tumor activity of JM-216 in patients with hormone refractory prostate cancer (HRPC) when given orally daily x 5 days. In this open label phase II study JM-216 was administered orally at the dose of 120 mg/m2/d for 5 days every 4 weeks. Patients continued on the therapy until evidence of disease progression or intolerable toxicity developed. Dose escalation and de-escalation were allowed according to patient's tolerance. Thirty-nine patients were enrolled onto the study and received a total of 155 courses (median 2, range 1-16) of JM-216. Dose delays (77% of courses) and dose reductions (31% of courses) were common and were mainly due to myelosupression. Treatment was discontinued in 5 patients due to treatment related toxicities. One patient developed myelodysplastic syndrome 11 months after the start of treatment. The most frequent grade III or higher adverse events included thrombocytopenia (54%), neutropenia (52%), anemia (24%) nausea (13%), vomiting (16%) and diarrhea (28%). PSA response was assessed in 32 patients, 10 (26%) had partial response, 14 (36%) had stable disease while PSA progression was seen in 8 (21%) patients. Of 20 (54%) patients with measurable disease two patients had a documented partial response. Although JM-216 had moderate activity in HRPC when given on daily basis for 5 days, it is associated with significant treatment related toxicities in this patient population.

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“…Approximately 80% to 90% of PCa are dependent on androgen/AR at initial diagnosis, and existing evidence suggests that an excessively activated androgen/AR signaling pathway is the key driver of CRPC . Consequently, androgen or AR has been the main target in establishing therapeutic approaches for PCa, while major pathways related to RT failure are associated with either highly or aberrantly activated AR signaling …”

Section: Introductionmentioning

confidence: 99%

Glucocorticoid receptor upregulation increases radioresistance and triggers androgen independence of prostate cancer

Chen

Ren³

et al. 2019

The Prostate

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Background Despite the overall success of radiotherapy, a significant number of patients develop radioresistance, which leads to local regional recurrence and distant metastasis. We studied whether repeated radiation treatment promotes androgen‐independent survival of prostate cancer (PCa) cells and their metastatic potential. We also studied whether glucocorticoid receptor (GR) increase in radioresistant cells is associated with acquisition of these aggressive characteristics. Methods Radioresistant LNCaP (LNCaPR18) and C4‐2 (C4‐2R26) PCa sublines were developed by repeated radiation treatments of parental cells. Levels and activations of androgen receptor (AR) and GR in radioresistant PCa cells and respective parental cells were investigated in quantitative real‐time polymerase chain reaction/Western blot analyses and immunofluorescence staining. Androgen‐independent survival of radioresistant cells was tested in in vitro cell growth assays and the castration‐resistant survival of these cell‐derived tumors were investigated in mouse xenografts. Results Higher GR levels, but lower AR levels were detected in radioresistant cells than in parental cells. Radiation‐induced GR upregulation was associated with increased intracellular cyclic adenosine monophosphate. As a consequence of GR activation, LNCaPR18 cells survived well in an androgen‐depleted culture condition while parental cells could not. Results of in vivo mouse studies showed survival of LNCaPR18 cell‐derived tumors in castrated mice while parental cell‐derived tumors regressed. The growth of LNCaPR18 cell‐derived tumors in castrated mice was impaired when treated with the anti‐GR agent mifepristone. In experiments with C4‐2/C4‐2R26 cell sets, GR activation in C4‐2R26 cells increased their metastatic potential. Conclusion GR activation in radioresistant cells mediates androgen independence and facilitates PCa progression.

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Oestrogen Therapy and Serum Cortisol in Carcinoma of the Prostate

Cited by 7 publications

References 27 publications

Effect of testosterone administration to men with prostate cancer is unpredictable: a word of caution and suggestions for a registry

Effect of testosterone administration to men with prostate cancer is unpredictable: a word of caution and suggestions for a registry

Phase II study of oral bis (aceto) ammine dichloro (cyclohexamine) platinum (IV) (JM-216, BMS-182751) given daily x 5 in hormone refractory prostate cancer (HRPC)

Glucocorticoid receptor upregulation increases radioresistance and triggers androgen independence of prostate cancer

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