Cabazitaxel versus abiraterone or enzalutamide in poor prognosis metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase II trial.

BACKGROUND: Treatment of poor prognosis metastatic castration-resistant prostate cancer (mCRPC) includes taxane chemotherapy and androgen receptor pathway inhibitors (ARPI). We sought to determine optimal treatment in this setting. PATIENTS AND METHODS: This multicentre, randomised, open-label, phase II trial recruited patients with ARPI-naive mCRPC and poor prognosis features (presence of liver metastases, progression to mCRPC after <12 months of androgen deprivation therapy, or ≥4 of 6 clinical criteria). Patients were randomly assigned 1 : 1 to receive cabazitaxel plus prednisone (group A) or physician's choice of enzalutamide or abiraterone plus prednisone (group B) at standard doses. Patients could cross over at progression. The primary endpoint was clinical benefit rate for first-line treatment (defined as prostate-specific antigen response ≥50%, radiographic response, or stable disease ≥12 weeks). RESULTS: Ninety-five patients were accrued (median follow-up 21.9 months). First-line clinical benefit rate was greater in group A versus group B (80% versus 62%, P = 0.039). Overall survival was not different between groups A and B (median 37.0 versus 15.5 months, hazard ratio (HR) = 0.58, P = 0.073) nor was time to progression (median 5.3 versus 2.8 months, HR = 0.87, P = 0.52). The most common first-line treatment-related grade ≥3 adverse events were neutropenia (cabazitaxel 32% versus ARPI 0%), diarrhoea (9% versus 0%), infection (9% versus 0%), and fatigue (7% versus 5%). Baseline circulating tumour DNA (ctDNA) fraction above the cohort median and on-treatment ctDNA increase were associated with shorter time to progression (HR = 2.38, P < 0.001; HR = 4.03, P < 0.001). Patients with >30% ctDNA fraction at baseline had markedly shorter overall survival than those with undetectable ctDNA (HR = 38.22, P < 0.001). CONCLUSIONS: Cabazitaxel was associated with a higher clinical benefit rate in patients with ARPI-naive poor prognosis mCRPC. ctDNA abundance was prognostic independent of clinical features, and holds promise as a stratification biomarker.

Impact of consultation recordings on patient-reported outcomes in patients with brain tumors: a parallel randomized controlled trial.

OBJECTIVE: We aimed to determine the impact of a primary treatment consultation recording on perception of being informed, satisfaction with cancer care, satisfaction with the oncologist, and psychological distress in patients with brain tumors. METHODS: This was a prospective, double-blind, parallel, randomized controlled trial conducted in 3 Canadian cities, in which patients who had their initial treatment consultation recorded were assigned to either receive their digital recording or not. It was hypothesized that patients who received their recording would realize statistically significant benefit on the outcomes of interest at 1 week, 3 months, and 6 months post-consultation in comparison to patients who did not receive their recording. Outcome measures included the following: Patient Satisfaction with Cancer Scale, Hospital Anxiety and Depression Scale, PrestMan Satisfaction with Doctor Scale, and Perception of Being Informed Scale. RESULTS: Of the 246 eligible patients, 133 participated (60.9% male; age M=52.4 years; 53.4% grade IV disease). Of these, 63 received their consultation recording and 70 did not. Intention-to-treat analysis showed that, compared to baseline, patients who received their consultation recording reported being more fully informed about their disease and treatment at 1 week post-consultation than patients who did not receive their recording (p = 0.007), but this finding was no longer significant at 3 and 6 months. There were no statistically significant differences observed between the two groups on the measures of satisfaction with cancer care, satisfaction with the doctor, and depression or anxiety at any assessment time point, though the study was under-powered. CONCLUSION: The study findings show that primary treatment consultation recordings may provide limited benefit beyond brain tumor patients' perception of being informed, despite being highly valued by these patients, and high listening rates among their significant others. The lack of statistical power should be considered when interpreting the findings. TRIAL REGISTRATION: ClinicalTrials.gov - NCT01866228.

The Effects of Exercise on Physical and Psychological Outcomes in Cancer Caregivers: Results From the RECHARGE Randomized Controlled Trial.

Background: Family caregivers to cancer patients are at risk for physical and psychological morbidity as a direct result of being in the caregiver role. Exercise as an intervention to support caregiver health and well-being has been tested in other caregiver populations; however, no randomized controlled trials testing the effects of an aerobic and resistance training program have been conducted where cancer caregivers only have participated. Purpose: To examine the effects of a 12-week exercise program on quality of life (Short Form 36 v2), psychological outcomes, physical activity levels, and physical fitness in caregivers to cancer patients. Methods: Seventy-seven caregivers were randomized to either an exercise intervention or wait-list control. Two participants in the exercise arm dropped out immediately after their baseline assessment. Outcome data for n = 77 participants were analyzed using intention-to-treat analysis with linear mixed models. Results: Significant group by time interaction effects were detected for exercise on the mental health component score of quality of life, self-reported weekly exercise levels, and the six-minute walk test. Small to medium effect sizes were detected on several outcomes including physical health component of quality of life (d = 0.36), mental health component of quality of life (d = 0.74), depression (d = 0.41), anxiety (d = 0.35), physical activity levels (d = 0.80), and the six-minute walk test (d = 0.21). Conclusions: The findings suggest that exercise may improve health and well-being and could be considered as an additional type of support offered to cancer caregivers. Clinical trial registration no: NCT02580461.

Creating an upward spiral: A qualitative study of caregivers' experience of participating in a structured physical activity programme.

Family caregivers' physical and emotional well-being may be negatively impacted while in the caregiver role. Interventions to support caregiver health have largely focused on psychological support, with only a few studies to date evaluating the role of exercise. Of the exercise studies conducted, there has been one qualitative study examining caregivers' perspectives on the value and impact of this type of intervention. This qualitative study was part of a larger mixed methods investigation including a randomised controlled trial investigating the effects of a 24-week exercise programme for cancer caregivers conducted in western Canada. We aimed to explore cancer family caregivers' experience of participating in a structured exercise programme. We conducted face-to-face interviews with 20 of the participants from the exercise intervention and analysed transcribed data using Thorne's interpretive description as a guiding framework. Two main patterns characterised the experiences of the caregivers. The metaphor of a downward spiral represented the experience of being in the caregiver role, while the metaphor of an upward spiral represented the experience of participating in the exercise programme. Our findings highlight that caregivers valued the exercise programme, experienced positivity through exercise and the group-based format, and noticed improvements to their physical and emotional well-being.

Low compliance with guidelines for re-staging in high-grade T1 bladder cancer and the potential impact on patient outcomes in the province of Alberta.

INTRODUCTION: Despite high-level evidence of benefit, early repeat resection (ERR) among high-grade T1 bladder cancer (HGT1-BC) patients remains low in several non-Canadian jurisdictions and rates in Canada are largely unreported. We evaluated rates of ERR and trends over time in Alberta. We also examined factors associated with uptake of ERR. METHODS: We conducted a retrospective review of data from all patients diagnosed with HGT1-BC from 2007 through 2011. Patients were identified from the Alberta Cancer Registry. Patients with a non-urothelial carcinoma of the bladder and those with invasion into the prostate or metastatic disease were excluded. We collected demographic and clinicopathologic information from patients' electronic medical records. RESULTS: A total of 600 patients diagnosed with HGT1-BC were included. Overall, 167 patients (27.8%) received an ERR; however, the rate increased in a non-linear fashion from 27.4% in 2007 to 37.8% in 2011. Factors associated with ERR included age <80 years (p=0.021) and centre at which the initial transurethral resection of bladder tumour (TURBT) was performed (p=0.013). Median overall survival (OS) was not reached, but five-year OS was 72.7% (95% CI 68.9, 76.5) for those who received an ERR and 55.3% (95% CI 52.5, 58.1) for those who did not. CONCLUSIONS: Use of ERR in patients with HGT1-BC is improving over time. Regional variation in practice suggests the need for implementation strategies (i.e., provincial clinical care pathways) to standardize practice and set indicators for future measurement and reporting. Targeted interventions would require further investigation around the reasons for variation in practice.

Predictors of referral for neoadjuvant chemotherapy prior to radical cystectomy for muscle-invasive bladder cancer and changes in practice over time.

INTRODUCTION: In patients with non-metastatic muscle-invasive bladder cancer (MIBC) fit for curative therapy, a multidisciplinary approach consisting is recommended. This approach includes local treatment (usually radical cystectomy), ideally combined with neoadjuvant chemotherapy (NACT). Despite a survival benefit with NACT, uptake remains low. We assessed NACT consultation in Alberta and examined associative factors, as well as the relationship to survival. METHODS: Patients with MIBC were identified through the Alberta Cancer Registry. Demographic and clinicopathologic information was collected from electronic medical records between 2007 and 2011. In addition to descriptive statistics, logistic regression was used to determine factors associated with receiving NACT consultation. Overall survival was described using a Kaplan-Meier estimate. RESULTS: Of the 315 radical cystectomy patients, 140 (45.1%, 95% confidence interval [CI] 39.5, 50.8) received NACT consultation. Patients ≥80 years (odds ratio [OR] 0.21, 95% CI 0.08, 0.57, p = 0.002) and those treated in Calgary (OR 0.11, 95% CI 0.05, 0.25, p < 0.001) were less likely to receive NACT consultation. The rate of NACT consultation increased steadily from 2007 to 2011 (OR 1.23, 95% CI 1.04, 1.45 per year of diagnosis, p = 0.018). After a median follow-up of 28.1 months (range: 14.6-50.3), median survival was 54.7 months for patients who received NACT consultation versus 31.2 months for those who did not (p = 0.030). CONCLUSIONS: NACT consultation in patients with MIBC undergoing radical cystectomy has improved over time; however, regional differences underscore the need for a standardized approach to NACT consultation, including common referral mechanisms.

Promoting consultation recording practice in oncology: identification of critical implementation factors and determination of patient benefit.

OBJECTIVE: The objectives of this implementation study were to (i) address the evidentiary, contextual, and facilitative mechanisms that serve to retard or promote the transfer and uptake of consultation recording use in oncology practice and (ii) follow patients during the first few days following receipt of the consultation recording to document, from the patient's perspective, the benefits realized from listening to the recording. METHODS: Nine medical and nine radiation oncologists from cancer centers in three Canadian cities (Calgary, Vancouver, and Winnipeg) recorded their primary consultations for 228 patients newly diagnosed with breast (n = 174) or prostate cancer (n = 54). The Digital Recording Use Semi-Structured Interview was conducted at 2 days and 1 week postconsultation. Each oncologist was provided a feedback letter summarizing the consultation recording benefits reported by their patients. RESULTS: Sixty-nine percent of patients listened to at least a portion of the recording within the first week following the consultation. Consultation recording favorableness ratings were high: 93.6% rated the intervention between 75 and 100 on a 100-point scale. Four main areas of benefit were reported: (i) anxiety reduction; (ii) enhanced retention of information; (iii) better informed decision making; and (iv) improved communication with family members. Eight fundamental components of successful implementation of consultation recording practice were identified. CONCLUSIONS: Further randomized trials are recommended, using standardized measures of the patient-reported benefit outcomes reported herein, to strengthen the evidence base for consultation recording use in oncology practice.

The influence of distress on knowledge transfer for men newly diagnosed with prostate cancer.

The purpose of this inquiry was to evaluate the efficacy of prostate cancer education sessions. Implementation of 3-h patient educational sessions was intended to provide men newly diagnosed with localized prostate cancer, who face difficult and complex decisions, information about potential treatment options. Fifty-seven men completed the distress thermometer assessment before the education session to assess baseline levels of distress. Seven of the men were interviewed post-educational session to determine the degree of knowledge transfer from the session. This study explored the efficacy of the patients' learning experience using an interpretive phenomenological research approach. Resulting data revealed that these patients, as adult learners, were distressed and that, despite the availability of pertinent medical content, the subject material was not learned as intended or readily understood. The conclusion drawn from this preliminary applied educational research study was that the education model used was less than efficacious at ensuring that sufficient knowledge transfer was achieved for medical treatment decision-making processes. These findings suggest a need for future research to explore the application of adult learning theories and approaches that may offer enhanced knowledge translation and transfer for prostate cancer education programs.

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

OBJECTIVE: 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. METHODS: The recorded consultations of 156 newly diagnosed prostate cancer patients from three Canadian cancer centers were examined using the Medical Interaction Process System (MIPS). The MIPS findings, independent observer ratings of patient, significant other, and oncologist affective behavior, and derived consultation ratios of patient centeredness, patient directedness, and psychosocial focus, were used to predict patient satisfaction with communication post-consultation and at 12-weeks post-consultation. RESULTS: Biomedical content categories were predominant in the consultations, accounting for 86% of utterances, followed by administrative (9%) and psychosocial (5%) utterances. Post-consultation satisfaction with communication was significantly lower for patients whose significant others were rated as more assertive during the consultation, and those rated as more anxious during the consultation. Patients who were rated as more anxious during the consultation, those with lower satisfaction with communication immediately post-consultation and those with shorter consultations were significantly less satisfied with communication at 12-weeks post-consultation. CONCLUSIONS: Adjuvant treatment consultations in prostate oncology are characterized by a high degree of information-giving by the physician, a predominance of biomedical discussion, and relatively minimal time addressing patients' psychosocial concerns. Patients may benefit from oncologists who address anxiety and emotional distress during the primary treatment consultation, allowing sufficient time to ensure that patients leave the consultation with their communication needs having been satisfied.

Furthering the prostate cancer screening debate (prostate cancer specific mortality and associated risks).

Screening for prostate cancer remains a contentious issue. As with other cancer screening programs, a key feature of the debate is verification of cancer-specific mortality reductions. Unfortunately the present evidence, two systematic reviews and six randomized controlled trials, have reported conflicting results. Furthermore, half of the studies are poor quality and the evidence is clouded by key weaknesses, including poor adherence to screening in the intervention arm or high rates of screening in the control arm. In high quality studies of prostate cancer screening (particularly prostate-specific antigen), in which actual compliance was anticipated in the study design, there is good evidence that prostate cancer mortality is reduced. The numbers needed to screen are at least as good as those of mammography for breast cancer and fecal occult blood testing for colorectal cancer. However, the risks associated with prostate cancer screening are considerable and must be weighed against the advantage of reduced cancer-specific mortality. Adverse events include 70% rate of false positives, important risks associated with prostate biopsy, and the serious consequences of prostate cancer treatment. The best evidence demonstrates prostate cancer screening will reduce prostate cancer mortality. It is time for the debate to move beyond this issue, and begin a well-informed discussion on the remaining complex issues associated with prostate cancer screening and appropriate management.

Progression-free survival as a clinical trial endpoint in advanced renal cell carcinoma.

Traditionally, overall survival (os) has been considered the "gold standard" for evaluating new systemic oncologic therapies, because death is easy to define, is easily compared across disease sites, and is not subject to investigator bias. However, as the available options for continuing therapy increase, the use of os as a clinical trial endpoint has become problematic because of the increasing crossover and contamination of trials. As a result, the approval of promising new therapies may be delayed.Many clinicians believe that progression-free survival (pfs) is a more viable option for evaluating new therapies in metastatic and advanced renal cell carcinoma. As with all endpoints, pfs has inherent biases, and those biases must be addressed to ensure that trial results are not compromised and that they will be accepted by regulatory authorities. In this paper, we examine the issues surrounding the use of pfs as a clinical trial endpoint, and we suggest solutions to ensure that data integrity is maintained.

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

PURPOSE: Over 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. METHODS: This paper is based on a systematic review of the literature pertaining to efforts to implement psychosocial oncology and supportive care interventions. RESULTS: The 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. CONCLUSIONS: The 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.

Study protocol: addressing evidence and context to facilitate transfer and uptake of consultation recording use in oncology: a knowledge translation implementation study.

BACKGROUND: The time period from diagnosis to the end of treatment is challenging for newly diagnosed cancer patients. Patients have a substantial need for information, decision aids, and psychosocial support. Recordings of initial oncology consultations improve information recall, reduce anxiety, enhance patient satisfaction with communication, and increase patients' perceptions that the essential aspects of their disease and treatment have been addressed during the consultation. Despite the research evidence supporting the provision of consultation recordings, uptake of this intervention into oncology practice has been slow. The primary aim of this project is to conduct an implementation study to explicate the contextual factors, including use of evidence, that facilitate and impede the transfer and uptake of consultation-recording use in a sample of patients newly diagnosed with breast or prostate cancer. METHODS: Sixteen oncologists from cancer centres in three Canadian cities will participate in this three-phase study. The preimplementation phase will be used to identify and address those factors that are fundamental to facilitating the smooth adoption and delivery of the intervention during the implementation phase. During the implementation phase, breast and prostate cancer patients will receive a recording of their initial oncology consultation to take home. Patient interviews will be conducted in the days following the consultation to gather feedback on the benefits of the intervention. Patients will complete the Digital Recording Use Semi-Structured Interview (DRUSSI) and be invited to participate in focus groups in which their experiences with the consultation recording will be explored. Oncologists will receive a summary letter detailing the benefits voiced by their patients. The postimplementation phase includes a conceptual framework development meeting and a seven-point dissemination strategy. DISCUSSION: Consultation recording has been used in oncology, family medicine, and other medicine specialties, and despite affirming evidence and probable applications to a large number of diseases and a variety of clinical contexts, clinical adoption of this intervention has been slow. The proposed study findings will advance our conceptual knowledge of the ways to enhance uptake of consultation recordings in oncology.

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. METHOD: Participants included 1057 newly diagnosed breast and prostate cancer patients from four Canadian cancer centers who partook in a randomized controlled trial examining the utility of providing patients with an audio-recording of their treatment planning consultation. A MANCOVA was performed to predict distress and cancer-specific quality of life at 12 weeks post-consultation based on control variables (patient age, education, residence, tumor size (breast sample), gleason score (prostate sample), and receipt of an initial treatment consultation recording), predictor variables (treatment type--chemotherapy, hormone therapy, radiation therapy; decisional role--active, collaborative, passive), and interactions between these predictors. RESULTS: Women who received chemotherapy and reported having played a more passive role in treatment decision making had significantly greater distress and lower cancer-specific quality of life at 12-week post-consultation. There were no statistically significant predictors of these outcomes identified for men with prostate cancer. CONCLUSION: Receipt of chemotherapy places women with breast cancer at risk for distress and reduced quality of life, but only for the subset of women who report playing a passive role in treatment decision making. Prospective, longitudinal studies are needed to confirm the present findings and to explicate the antecedents, composition, and consequences of the 'passive' decisional role during the treatment phase of the cancer trajectory.

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. METHODS: The recorded consultations of 172 newly diagnosed breast cancer patients from four Canadian cancer centers were randomly drawn from a larger subset of 481 recordings and examined by three coders using the Medical Interaction Process System (MIPS); a system that categorizes the content and mode of each distinct utterance. The MIPS findings, independent observer ratings of patient and oncologist affective behavior, and derived consultation ratios of patient centeredness, patient directedness, and psychosocial focus, were used to predict patient satisfaction with communication post-consultation and at 12-weeks post-consultation. RESULTS: Biomedical content categories were predominant in the consultations, accounting for 88% of all utterances, followed by administrative (6%) and psychosocial (6%) utterances. Post-consultation satisfaction with communication was significantly higher for older patients, those with smaller primary tumors and those with longer consultations. Smaller tumor, lack of patient assertiveness during the treatment consultation and having the consultation with a radiation rather than medical oncologist were significantly predictive of greater satisfaction at 12-weeks post-consultation. CONCLUSIONS: Adjuvant treatment consultations are characterized by a high degree of information-giving by the physician, a predominance of biomedical discussion and relatively minimal time addressing patients' psychosocial concerns. Controlled trials are needed to further identify and address the contextual features of these consultations that enhance patient satisfaction.

Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study.

PURPOSE: There are no robust data on prognostic factors for overall survival (OS) in patients with metastatic renal cell carcinoma (RCC) treated with vascular endothelial growth factor (VEGF) -targeted therapy. METHODS: Baseline characteristics and outcomes on 645 patients with anti-VEGF therapy-naïve metastatic RCC were collected from three US and four Canadian cancer centers. Cox proportional hazards regression, followed by bootstrap validation, was used to identify independent prognostic factors for OS. RESULTS: The median OS for the whole cohort was 22 months (95% CI, 20.2 to 26.5 months), and the median follow-up was 24.5 months. Overall, 396, 200, and 49 patients were treated with sunitinib, sorafenib, and bevacizumab, respectively. Four of the five adverse prognostic factors according to the Memorial Sloan-Kettering Cancer Center (MSKCC) were independent predictors of short survival: hemoglobin less than the lower limit of normal (P < .0001), corrected calcium greater than the upper limit of normal (ULN; P = .0006), Karnofsky performance status less than 80% (P < .0001), and time from diagnosis to treatment of less than 1 year (P = .01). In addition, neutrophils greater than the ULN (P < .0001) and platelets greater than the ULN (P = .01) were independent adverse prognostic factors. Patients were segregated into three risk categories: the favorable-risk group (no prognostic factors; n = 133), in which median OS (mOS) was not reached and 2-year OS (2y OS) was 75%; the intermediate-risk group (one or two prognostic factors; n = 301), in which mOS was 27 months and 2y OS was 53%; and the poor-risk group (three to six prognostic factors; n = 152), in which mOS was 8.8 months and 2y OS was 7% (log-rank P < .0001). The C-index was 0.73. CONCLUSION: This model validates components of the MSKCC model with the addition of platelet and neutrophil counts and can be incorporated into patient care and into clinical trials that use VEGF-targeted agents.

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

BACKGROUND: 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. METHODS: Baseline plasma samples were stored (-80 degrees C) from 160 of 250 patients enrolled in the AIPC Study of Calcitriol ENhancing Taxotere (ASCENT) trial, a randomized, placebo-controlled trial comparing weekly docetaxel plus high-dose calcitriol with weekly docetaxel. Multiplex immunoassays measured 16 cytokine, chemokine, cardiovascular, or inflammatory markers. The Cox proportional hazards model was used to assess associations between baseline biomarkers, clinical characteristics, and survival. Logistic regression was used for analyses of associations with prostate-specific antigen (PSA) decline. RESULTS: C-reactive protein (CRP) was found to be significantly predictive of a shorter overall survival (hazards ratio [HR] of 1.41 for each natural logarithm [ln] [CRP] increase; 95% confidence interval [95% CI], 1.20-1.65 [P < .0001]). When CRP (continuous) was entered into a multivariate model using 13 baseline clinical variables, only elevated CRP remained a significant predictor (P < .0001) of shorter overall survival. When categorized as normal (8 mg/L), elevated CRP was found to be a significant predictor of shorter overall survival (HR of 2.96; 95% CI, 1.52-5.77 [P = .001]), as was hemoglobin (P = .007). Elevated CRP was also associated with a lower probability of PSA decline (odds ratio of 0.74 for each ln(CRP) increase; 95% CI, 0.60-0.92 [P = .007]). CONCLUSIONS.: Elevated plasma CRP concentrations appear to be a strong predictor of poor survival and lower probability of PSA response to treatment in patients with AIPC who are receiving docetaxel-based therapy.

A phase II study of sorafenib in patients with chemo-naive castration-resistant prostate cancer.

BACKGROUND: The purpose of this trial was to evaluate the antitumor activity of sorafenib, a multikinase inhibitor of cell proliferation and angiogenesis, in patients with castration-resistant prostate cancer. PATIENTS AND METHODS: This was a multicenter, two-stage, phase II study. Sorafenib 400 mg was administered orally twice daily continuously. Primary end point was prostate-specific antigen (PSA) 'response' defined as a > or =50% decrease for > or =4 weeks. RESULTS: In all, 28 patients were enrolled. Eastern Cooperative Oncology Group performance status was zero or one in 19 and 9 patients. Two patients had no metastases, and 26 had bone and/or lymph node disease. A median of two cycles (range 1-8) was delivered. Adverse events were typical for sorafenib. The PSA response rate was 3.6% [95% confidence interval (CI) 0.1% to 18.3%] with response occurring in one patient (baseline = 10 000 and nadir = 1643 microg/l). No measurable disease responses occurred in eight patients. Time to PSA progression was 2.3 months (95% CI 1.8-6.4). Of 16 patients who discontinued sorafenib and then did not receive any immediate therapy, 10 had postdiscontinuation PSA declines of 7%-52%. CONCLUSIONS: Sorafenib has limited activity using current PSA criteria. The declines in PSA observed on treatment discontinuation indicate an effect on PSA production/secretion. Further study may be warranted but needs to consider the limitations of PSA as an indicator of progression and response.