Randomized, open-label phase III trial of docetaxel plus high-dose calcitriol versus docetaxel plus prednisone for patients with castration-resistant prostate cancer.

PURPOSE: To compare the efficacy and safety of docetaxel plus high-dose calcitriol (DN-101) to docetaxel plus prednisone in an open-label phase III trial. PATIENTS AND METHODS: Nine hundred fifty-three men with metastatic castration-resistant prostate cancer (CRPC) were randomly assigned to Androgen-Independent Prostate Cancer Study of Calcitriol Enhancing Taxotere (ASCENT; 45 µg DN-101, 36 mg/m(2) docetaxel, and 24 mg dexamethasone weekly for 3 of every 4 weeks) or control (5 mg prednisone twice daily with 75 mg/m(2) docetaxel and 24 mg dexamethasone every 3 weeks) arms. The primary end point was overall survival (OS), assessed by the Kaplan-Meier method. RESULTS: At an interim analysis, more deaths were noted in the ASCENT arm, and the trial was halted. The median-follow-up for patients alive at last assessment was 11.7 months. Median OS was 17.8 months (95% CI, 16.0 to 19.5) in the ASCENT arm and 20.2 months (95% CI, 18.8 to 23.0) in the control arm (log-rank P = .002). Survival remained inferior after adjusting for baseline variables (hazard ratio, 1.33; P = .019). The two arms were similar in rates of total and serious adverse events. The most frequent adverse events were GI (reported in 75% of patients), and blood and lymphatic disorders (48%). Docetaxel toxicity leading to dose modification was more frequent in the ASCENT (31%) than in the control arm (15%). CONCLUSION: ASCENT treatment was associated with shorter survival than the control. This difference might be due to either weekly docetaxel dosing, which, in a prior study, showed a trend toward inferior survival compared with an every-3-weeks regimen, or DN-101 therapy.

Power calculations for preclinical studies using a K-sample rank test and the Lehmann alternative hypothesis.

Power calculations in a small sample comparative study, with a continuous outcome measure, are typically undertaken using the asymptotic distribution of the test statistic. When the sample size is small, this asymptotic result can be a poor approximation. An alternative approach, using a rank based test statistic, is an exact power calculation. When the number of groups is greater than two, the number of calculations required to perform an exact power calculation is prohibitive. To reduce the computational burden, a Monte Carlo resampling procedure is used to approximate the exact power function of a k-sample rank test statistic under the family of Lehmann alternative hypotheses. The motivating example for this approach is the design of animal studies, where the number of animals per group is typically small.

The impact of gross total resection on local control and survival in high-risk neuroblastoma.

BACKGROUND/PURPOSE: Gross total resection of the primary tumor in treatment of high-risk neuroblastoma remains controversial. Furthermore, there are few reports of the effect of primary tumor resection on local control as opposed to overall survival. The authors reviewed their institutional experience to assess the effect of primary tumor resection on local control and overall survival. METHODS: A total of 141 patients were treated on protocol between November 1, 1979 and June 25, 2002 and are the subject of this report. Gross total resection was assessed by review of operative notes, postoperative computerized axial tomograms, and postoperative meta-iodobenzyl guanidine (MIBG)1 scans when available. RESULTS: The median age was 3.3 years, and all patients were International Neuroblastoma Staging System (INSS) stage 4 with 79% having metastases to cortical bone. The primary site was the adrenal gland in 74%, the central abdominal compartment in 13%, the posterior mediastinum in 7%, and other sites in 6%. Gross total resection was accomplished in 103 (73%) but was more than 90% for the last 3 protocols. Five kidneys were lost overall. The probability of local progression was 50% in unresected patients compared with 10% in patients undergoing gross total resection (P <.01). Overall survival rate in resected patients was 50% compared with 11% in unresected patients (P <.01). CONCLUSIONS: Our data indicate that local control and overall survival rate are correlated with gross total resection of the primary tumor in high-risk neuroblastoma. Gross total resection should be part of the management of stage 4 neuroblastoma in patients greater than 1 year of age.