Testosterone recovery after prolonged androgen suppression in patients with prostate cancer.

PURPOSE: We prospectively examined the extent and timing of testosterone recovery in patients with prostate cancer treated with 2 years of androgen suppression. MATERIALS AND METHODS: A total of 153 patients with pT3N0M0 prostate cancer or positive margins after radical prostatectomy, or with prostate specific antigen relapse were treated with radiation to the prostate bed plus 2 years of androgen suppression as per a phase II study. Androgen suppression consisted of nilutamide for 4 weeks plus busereline acetate bimonthly for 2 years. Serum testosterone was measured at baseline, every 4 months during androgen suppression and every 6 months after androgen suppression during followup. Testosterone recovery to supracastrate levels, and to baseline and/or normal levels was estimated using Kaplan-Meier methods. Prognostic factors for testosterone recovery were examined. RESULTS: A total of 121 patients who completed 2 years of androgen suppression and 20 patients who received shorter durations of androgen suppression (median 16 months) were available for testosterone recovery analysis. Median followup after finishing androgen suppression was 38.9 months. All patients achieved castrate levels on androgen suppression. At 36 months after completion of androgen suppression 93.2% and 71.5% had recovery to supracastrate (median time 12.7 months), and to baseline and/or normal testosterone levels (median time 22.3 months), respectively. On multivariate analysis younger age (younger than 60 years, p = 0.0006) and shorter androgen suppression duration (less than 2 years, p = 0.028) were prognostic for faster recovery to baseline and/or normal testosterone levels after adjusting for baseline testosterone levels (p = 0.447). CONCLUSIONS: Testosterone recovery after prolonged androgen suppression is protracted. Older age and longer duration of androgen suppression result in significantly longer recovery times to baseline and/or normal testosterone levels.

Single fraction radiotherapy versus multiple fraction radiotherapy for bone metastases in prostate cancer patients: comparative effectiveness.

External beam radiotherapy (EBRT) is an effective treatment for symptomatic bone metastases from a variety of primary malignancies. Previous meta-analyses and systematic reviews have reported on the efficacy of EBRT on bone metastases from multiple primaries. This review is focused on the comparative effectiveness of single fraction radiotherapy versus multiple fraction radiotherapy for bone metastases in prostate cancer patients.

Susceptibility to fatty acid-induced ß-cell dysfunction is enhanced in prediabetic diabetes-prone biobreeding rats: a potential link between ß-cell lipotoxicity and islet inflammation.

ß-Cell lipotoxicity is thought to play an important role in the development of type 2 diabetes. However, no study has examined its role in type 1 diabetes, which could be clinically relevant for slow-onset type 1 diabetes. Reports of enhanced cytokine toxicity in fat-laden islets are consistent with the hypothesis that lipid and cytokine toxicity may be synergistic. Thus, ß-cell lipotoxicity could be enhanced in models of autoimmune diabetes. To determine this, we examined the effects of prolonged free fatty acids elevation on ß-cell secretory function in the prediabetic diabetes-prone BioBreeding (dp-BB) rat, its diabetes-resistant BioBreeding (dr-BB) control, and normal Wistar-Furth (WF) rats. Rats received a 48-h iv infusion of saline or Intralipid plus heparin (IH) (to elevate free fatty acid levels ~2-fold) followed by hyperglycemic clamp or islet secretion studies ex vivo. IH significantly decreased ß-cell function, assessed both by the disposition index (insulin secretion corrected for IH-induced insulin resistance) and in isolated islets, in dp-BB, but not in dr-BB or WF, rats, and the effect of IH was inhibited by the antioxidant N-acetylcysteine. Furthermore, IH significantly increased islet cytokine mRNA and plasma cytokine levels (monocyte chemoattractant protein-1 and IL-10) in dp-BB, but not in dr-BB or WF, rats. All dp-BB rats had mononuclear infiltration of islets, which was absent in dr-BB and WF rats. In conclusion, the presence of insulitis was permissive for IH-induced ß-cell dysfunction in the BB rat, which suggests a link between ß-cell lipotoxicity and islet inflammation.

Alterations in hormone levels after adjuvant chemoradiation in male rectal cancer patients.

PURPOSE: To evaluate follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels after postoperative chemoradiation in men with rectal cancer. METHODS AND MATERIALS: Forty-three men with rectal cancer had baseline and postchemoradiation FSH, LH, and testosterone measured. Adjuvant chemoradiation consisted of two 5-day cycles of bolus 5-fluorouracil (5-FU) every 4 weeks at a dose of 500 mg/m(2)/d followed by concurrent chemoradiation followed by two additional 5-day cycles of 5-FU at a dose of 450 mg/m(2)/d. Continuous-infusion 5-FU at 225 mg/m(2)/d was given during radiation. Pelvic radiation consisted of a three- or four-field technique with a median dose of 54.0 Gy in 30 fractions. RESULTS: Median follow-up was 6.1 years. Mean baseline FSH levels increased from 5.3 to a peak of 23.9 IU/L (p < 0.001) 13-24 months after chemoradiation. Mean baseline LH levels increased from 4.3 to a peak of 8.5 IU/L (p < 0.001) within 6 months after chemoradiation. Mean testosterone levels decreased from 15.4 nmol/L at baseline to 8.0 nmol/L more than 4 years after chemoradiation. Mean testosterone to mean LH ratio decreased from 4.4 at baseline to 1.1 after 48 months posttreatment, suggesting a continued decrease in Leydig cell function with time. Testicular dose was measured in 5 patients. Median dose was 4 Gy (range, 1.5-8.9 Gy). CONCLUSIONS: Chemoradiation in men with rectal cancer causes persistent increases in FSH and LH levels and decreases in testosterone levels.