Final results of the Canadian prospective phase II trial of intermittent androgen suppression for men in biochemical recurrence after radiotherapy for locally advanced prostate cancer

Abstract

The impact of reduced‐intensity conditioning (RIC) on the outcomes of hematopoietic cell transplantation (HCT) from unrelated ‐donors (UD) remains to be determined. We therefore assessed 128 patients, aged 16 to 66 years, with acute leukemia (n = 105) or myelodysplastic syndrome (n = 23) in a UD‐HCT trial using RIC with busulfan, fludarabine, and antithymocyte globulin. Patients were transplanted with unmanipulated bone marrow (BM, n = 41) or mobilized peripheral blood mononuclear cells (M‐PB, n = 87) and received cyclosporine and methotrexate for graft‐versus‐host disease (GVHD) prophylaxis. After a median follow‐up of 26.7 months (range, 5.9−70.7 months) in surviving patients, 19 patients had died without progression/recurrence of underlying disease, giving a cumulative incidence of transplantation‐related mortality (TRM) of 17% (95% confidence interval, 11%–27%; 1‐year TRM, 14%). Graft failure (n = 7) and infections (n = 5) were the most common causes of TRM. Only three patients died due to GVHD (acute, one; chronic, two). Graft failure, which occurred in eight patients, showed a significant correlation with graft source (BM, 6/41 vs. M‐PB, 2/87; P = 0.009). Donor‐patient HLA‐disparity did not correlate with GVHD, 1‐year TRM, and graft failure. RIC containing antithymocyte globulin led to decreased GVHD‐associated, as well as overall, TRM after UD‐HCT. This trial is registered at http://www.clinicaltrials.gov as NCT00627666. Am. J. Hematol. 86:399–405,2011. © 2011 Wiley‐Liss, Inc.

Mathematical modelling of prostate cancer growth and its application to hormone therapy

“…In figure 5a,b, the mean length of the off-treatment periods decreases with each succeeding cycle. This trend can be found in the clinical data (Bruchovsky et al 2006). However, the trend is not applicable to the case when the initial testosterone level is relatively high as shown in figure 5c.…”

“…After reviewing mathematical modelling of IAS for prostate cancer, we have presented a stochastic model and shown that it is successful in reproducing statistical features of the time course of serum PSA in clinical trials (Bruchovsky et al 2006(Bruchovsky et al , 2007, such as the shortening of the off-treatment periods with more on-and off-treatment cycles and the inverse relationship between the serum PSA nadir level and the length of the off-treatment interval. However, the stochastic model is not able to replicate the biphasic decrease of the serum PSA level.…”

“…It should be noted that the patient is withdrawn from the study if the PSA level is not less than r 0 at 36 weeks after resumption of treatment. The values of the clinically controllable parameters r 1 and r 0 are fixed in numerical simulations according to the protocol used in clinical trials (Bruchovsky et al 2006). …”

“…The biochemical results from a prospective phase II study of IAS (Bruchovsky et al 2006(Bruchovsky et al , 2007 were analysed for correlations to the onset of hormone-refractory disease. The analyses of time courses of the serum PSA and testosterone levels suggested some statistical trends.…”

“…Therefore, it is important to investigate how the IAS therapy model is sensitive to stochastic noise. This is why the first purpose of this article is to develop a stochastic differential equation model with dynamical and observational noise under the protocol of intermittent hormone therapy used in recent clinical study (Bruchovsky et al 2006(Bruchovsky et al , 2007.…”