J. Dean Ruether

Double-Blinded Randomized Study of High-Dose Calcitriol Plus Docetaxel Compared With Placebo Plus Docetaxel in Androgen-Independent Prostate Cancer: A Report From the ASCENT Investigators

PURPOSE To compare the safety and activity of DN-101, a new high-dose oral formulation of calcitriol designed for cancer therapy, and docetaxel with placebo and docetaxel. PATIENTS AND METHODS Patients with progressive metastatic androgen-independent prostate cancer and adequate organ function received weekly docetaxel 36 mg/m2 intravenously for 3 weeks of a 4-week cycle combined with either 45 microg DN-101 or placebo taken orally 1 day before docetaxel. The primary end point was prostate-specific antigen (PSA) response within 6 months of enrollment, defined as a 50% reduction confirmed at least 4 weeks later. RESULTS Two hundred fifty patients were randomly assigned. Baseline characteristics were similar in both arms. Within 6 months, PSA responses were seen in 58% in DN-101 patients and 49% in placebo patients (P = .16). Overall, PSA response rates were 63% (DN-101) and 52% (placebo), P = .07. Patients in the DN-101 group had a hazard ratio for death of 0.67 (P = .04) in a multivariate analysis that included baseline hemoglobin and performance status. Median survival has not been reached for the DN-101 arm and is estimated to be 24.5 months using the hazard ratio, compared with 16.4 months for placebo. Grade 3/4 adverse events occurred in 58% of DN-101 patients and in 70% of placebo-treated patients (P = .07). Most common grade 3/4 toxicities for DN-101 versus placebo were neutropenia (10% v 8%), fatigue (8% v 16%), infection (8% v 13%), and hyperglycemia (6% v 12%). CONCLUSION This study suggests that DN-101 treatment was associated with improved survival, but this will require confirmation because survival was not a primary end point. The addition of weekly DN-101 did not increase the toxicity of weekly docetaxel.

Intermittent chemotherapy in patients with metastatic androgen-independent prostate cancer: results from ASCENT, a double-blinded, randomized comparison of high-dose calcitriol plus docetaxel with placebo plus docetaxel.

Survival in patients with metastatic, chemotherapy‐naive, androgen‐independent prostate cancer (AIPC) is improved with 10 to 12 cycles of docetaxel‐containing chemotherapy but further management is undefined. In the current study, the authors examined retreatment with the same regimen after a treatment holiday.

C-reactive protein as a prognostic marker for men with androgen-independent prostate cancer: results from the ASCENT trial.

Studies of cancer risk and molecular carcinogenesis suggest a role for inflammation in cancer development and progression. The authors sought to determine whether specific blood proteins associated with inflammation predict for outcomes in men with metastatic androgen‐independent prostate cancer (AIPC) who are initiating docetaxel‐based chemotherapy.

Psychosocial barriers to active surveillance for the management of early prostate cancer and a strategy for increased acceptance.

To review the psychosocial needs of men undergoing active surveillance (AS, the monitoring of early prostate cancer, with curative intervention only if the disease significantly progresses) for prostate cancer, and barriers to its uptake.

Impact of Providing Audiotapes of Primary Adjuvant Treatment Consultations to Women With Breast Cancer: A Multisite, Randomized, Controlled Trial

PURPOSE Women with breast cancer were provided with an audiotape of their primary adjuvant treatment consultation, and the following patient outcomes were measured at 12 weeks postconsultation: perceived degree of information provision, audiotape satisfaction and use, communication satisfaction with oncologist, mood state, and cancer-specific quality of life. PATIENTS AND METHODS Participants included 628 women newly diagnosed with breast cancer and 40 oncologists from six cancer centers in Canada. The patients were block randomized to one of four consultation groups: standard care control, not audiotaped; audiotaped, no audiotape given; audiotaped, patient given audiotape; and audiotaped, patient offered choice of receiving audiotape or not. RESULTS Patients receiving the consultation audiotape had significantly better recall of having discussed side effects of treatment than patients who did not receive the audiotape. Audiotape benefit was not significantly related to patient satisfaction with communication, mood state, or quality of life at 12 weeks postconsultation, and was not significantly affected by choice of receiving the audiotape. Patients rated the audiotape intervention positively, with an average score of 83.9 of 100. CONCLUSION Audiotape provision benefits patients by facilitating their perception of being informed about treatment side effects, but does not significantly influence patient satisfaction with communication, mood state, or quality of life.

Predictors of distress and quality of life in patients undergoing cancer therapy: impact of treatment type and decisional role.

Purpose: The purpose of this secondary investigation was to examine the impact of the type of treatment received and the perceived role in treatment decision making in predicting distress and cancer‐specific quality of life in patients newly diagnosed with breast or prostate cancer.

High dose calcitriol may reduce thrombosis in cancer patients

The incidence of venous and arterial thrombosis in a placebo‐controlled randomised trial of DN‐101 (high dose calcitriol) with docetaxel versus docetaxel was compared. Of the 13 thrombotic events observed in the 250 patients enroled in this study, two occurred in DN‐101 and 11 in placebo‐treated patients (P = 0·01). This difference remained significant after adjustment for baseline history of thrombosis, atrial fibrillation and use of anti‐thrombotic agents. In vitro and vitamin D receptor (VDR) knockout mouse studies predict that nanomolar concentrations of calcitriol may act as an antithrombotic agent. We report the first clinical observation that supports this hypothesis in humans.

Behind closed doors: systematic analysis of breast cancer consultation communication and predictors of satisfaction with communication

Objective: The purpose of this investigation was to explicate the content of primary adjuvant treatment consultations in breast oncology and examine the predictive relationships between patient and oncologist consultation factors and patient satisfaction with communication.

Facilitating the implementation of empirically valid interventions in psychosocial oncology and supportive care

PurposeOver the past two decades, the fields of psychosocial oncology and supportive care have seen clinically effective tools as underutilized despite proven benefits to cancer patients and their families. The purpose of this paper is to discuss the reasons for the failure of psychosocial and supportive care interventions in oncology to realize broad clinical implementation and to demonstrate how a knowledge management framework offers several advantages for increasing the probability of successful implementation.MethodsThis paper is based on a systematic review of the literature pertaining to efforts to implement psychosocial oncology and supportive care interventions.ResultsThe struggle to develop, implement, and evaluate promising psychosocial oncology and supportive care innovations has moved academic thought toward the development of models and theories concerning the best ways to move new knowledge into clinical practice. There are critical and common barriers to the successful transfer and implementation of promising interventions, and implementation efforts may be maximized by using knowledge management frameworks to systematically identify and address these barriers.ConclusionsThe successful implementation of empirically promising interventions requires research networks and practice groups to work together in a concerted, theory-guided effort to identify and address the contextual factors most relevant to any particular intervention. The growing support of knowledge implementation activities by research funders, policy-makers, opinion leaders, and advocates of psychosocial and supportive care interventions is a positive move in this direction.

Behind closed doors II: systematic analysis of prostate cancer patients' primary treatment consultations with radiation oncologists and predictors of satisfaction with communication

The purpose of this investigation was to explicate the content of primary treatment consultations in prostate oncology and examine the predictive relationships between patient, significant other, and oncologist consultation factors and patient satisfaction with communication.