A phase I-II study of docetaxel and atrasentan in men with castration-resistant metastatic prostate cancer.

PURPOSE: The primary aims of this phase I-II study were to determine the maximum tolerated dose, dose-limiting toxicity, pharmacokinetics, and preliminary efficacy of the combination of docetaxel and the endothelin A receptor antagonist atrasentan as first-line treatment for men with metastatic castration-resistant prostate cancer. EXPERIMENTAL DESIGN: Patients were treated with docetaxel at doses ranging from 60 to 75 mg/m(2) every 21 days, with daily oral atrasentan 10 mg starting on day 3. Patients were treated until evidence of disease progression or unacceptable toxicity. RESULTS: Thirty-one patients were enrolled over three docetaxel dose levels (8 at 60 mg/m(2), 19 at 70 mg/m(2), and 4 at 75 mg/m(2)) including dose expansion at 70 mg/m(2). The maximum tolerated dose of docetaxel was 70 to 75 mg/m(2). Drug-related grade 3-4 toxicities included neutropenia (50-63%) and febrile neutropenia (16-25%); other grade 1-2 toxicities included fatigue, peripheral edema, diarrhea, headache, rhinitis, anorexia, and nausea. Confirmed prostate-specific antigen (PSA) responses were observed in 23% [95% confidence interval (95% CI), 10-41%]; the rate of >30% declines in PSA was 35% (95% CI, 19-55%). Median overall survival was 17.6 months (95% CI, 13.0-23.2) and median progression-free survival was 4.2 months (95% CI, 2.3-5.8). Significant declines in bone alkaline phosphatase and serum N-telopeptides were observed with therapy. CONCLUSIONS: The maximum tolerated dose of every-3-week docetaxel with 10 mg atrasentan is 70 to 75 mg/m(2). Overall survival and progression-free survival are comparable to that seen with docetaxel and prednisone, whereas the rates of PSA decline are slightly lower than expected. A phase III study of this combination with prednisone has been initiated and is ongoing.

Use of general clinical research centers for nursing research.

This study examines to what extent academic nursing faculty members understand the purpose of general clinic research centers (GCRCs) and use this resource in their programs of research. GCRCs provide a controlled research-oriented infrastructure to conduct safe, innovative, and multidisciplinary studies. Survey questionnaires were sent to associate deans of research at schools of nursing accredited by the Commission on Collegiate Nursing Education or the National League for Nursing Accrediting Commission within 60 miles of a GCRC. They were asked to distribute questionnaires to 20% of faculty members. Of the 186 nurse faculty members responding, 85% had not conducted research at a GCRC as a principal investigator and 69% of the sample reported that their colleges or universities do not make information about GCRCs available to new faculty. Making greater use of this valuable resource allows nurse researchers to become more involved in developing new knowledge and testing interventions and in psychological and physiologic measurements, thus doing more to fulfill the mission of nursing research and increasing the involvement of nurses in the broader community of health science research.

Improving outcomes with novel therapies for patients with newly diagnosed renal cell carcinoma.

With the approval of sunitinib and sorafenib, 2 new multitargeted tyrosine kinase inhibitors, for the treatment of advanced renal cell carcinoma (RCC), the natural history and prognosis of patients with this disease has significantly improved. These drugs were approved based upon clinical data demonstrating robust, unprecedented response rates in one case and dramatic prolongation of progression-free survival in the other. In both cases, these results were seen in study patients in whom standard therapy had failed and who, on average, carried substantial disease burden. Important challenges today include integrating these therapies with other standard therapeutic options and into other advanced-stage RCC patient populations. This article addresses current data and practice patterns regarding the clinical use of tyrosine kinase inhibitors in patients with advanced-stage RCC, including dose modifications and alternative dosing, the current role of debulking nephrectomy, and use in patients with indolent disease. Finally, a summary of the more common side effects and management strategies for these is also discussed. Ultimately, more clinical data is needed to address the chronic use of these agents alone, in combination with other agents, with radiation therapy, and in sequence.