Susan Masson

Second-line treatment options in metastatic castration-resistant prostate cancer: a comparison of key trials with recently approved agents.

Standard first-line treatment for metastatic castration-resistant prostate cancer (mCRPC) is docetaxel plus prednisone; however, patients will usually experience disease progression during or after docetaxel treatment due to inherent or acquired resistance. Before 2010, second-line options for mCRPC were limited. However, cabazitaxel, abiraterone acetate and enzalutamide have since been approved for patients with mCRPC whose disease has progressed during or after receiving docetaxel, based on the Phase III trials TROPIC, COU-AA-301 and AFFIRM. In all three trials, an overall survival benefit (primary endpoint) was seen in the experimental arm compared with the control arm: 15.1 vs. 12.7months for cabazitaxel plus prednisone compared with mitoxantrone plus prednisone in TROPIC (hazard ratio [HR] 0.70; P<0.0001); 14.8 vs. 10.9months for abiraterone acetateplus prednisone compared with placebo plus prednisone in COU-AA-301 (HR 0.65; P<0.001); and 18.4 vs. 13.6months for enzalutamide compared with placebo alone in AFFIRM (0.63; P<0.001). However, differences in patient populations, comparators, and selection and/or definition of secondary endpoints make it difficult to draw direct cross-trial comparisons. Radium-223 dichloride has also been approved for patients with mCRPC with metastases to bone but not other organs. To date, no comparative trials or sequencing studies with newer agents have been performed. Without such data, treatment decisions must be based on evaluation of the existing evidence. This commentary compares and contrasts study designs and key data from each of these Phase III trials, and also discusses recent and ongoing clinical trials with new agents in the first- and second-line settings in mCRPC.

Final quality of life and safety data for patients with metastatic castration-resistant prostate cancer treated with cabazitaxel in the UK Early Access Programme (EAP) (NCT01254279)

To compile the safety profile and quality of life (QoL) data for patients with metastatic castration‐resistant prostate cancer (mCRPC) treated with cabazitaxel in the UK Early Access Programme (UK EAP).

Cabazitaxel for metastatic castration-resistant prostate cancer (mCRPC): Interim safety and quality-of-life (QOL) data from the U.K. early access program (NCT01254279).

44 Background: Cabazitaxel, a tubulin-binding taxane, improved survival in mCRPC in the TROPIC trial. Notable toxicities were neutropenia and diarrhoea. We report interim safety and QOL data from a single arm multicentre open label study providing early access to cabazitaxel in the UK. METHODS Patients recruited from 12 centres received cabazitaxel 25mg/m2 intravenously every 3 weeks and prednisolone 10mg daily. Safety assessments were performed before each cycle. Patients completed the EQ-5D questionnaire and health state visual analogue scale (VAS) at baseline and at alternate cycles. Patients recruited before March 31st 2011 are included in the safety analysis. QOL data collected before July 31st 2011 at baseline (n=62), cycle 2 (n=50) and cycle 4 (n=26) are included. RESULTS Median age was 68 years; 24% were aged over 75 years. 93% had bone metastases. 50% had experienced disease progression during or within 3 months of docetaxel and the remaining 50% within 3-6 months. A median of 3 cycles of cabazitaxel were completed with 99% relative dose intensity. 83% continued cabazitaxel at the time of safety analysis. 7 patients stopped before completing the full course, 5 of these were due to disease progression. One treatment related death occurred within 30 days of the last cabazitaxel infusion (2.4%). 85% of patients received granulocyte-colony stimulating factor prophylaxis from cycle 1. The proportion of patients reporting no pain or discomfort increased between baseline, cycle 2 and cycle 4 (22.6% to 38% to 50%). Anxiety and depression, mobility and self-care scores from EQ-5D were stable. Median VAS health state increased from baseline (75%) to cycle 4 (79%). CONCLUSIONS Improvements in pain control and health states were reported during early stages of cabazitaxel treatment. Other EQ-5D QOL measures were stable. Severe toxicity was rare. Results will be updated from final analysis in late 2011. [Table: see text].

Metastatic castrate‐resistant prostate cancer: dawn of a new age of management

Whats known on the subject? and What does the study add?

HDR Brachytherapy in the Management of High-Risk Prostate Cancer

High-dose-rate (HDR) brachytherapy is used with increasing frequency for the treatment of prostate cancer. It is a technique which allows delivery of large individual fractions to the prostate without exposing adjacent normal tissues to unacceptable toxicity. This approach is particularly favourable in prostate cancer where tumours are highly sensitive to dose escalation and to increases in radiotherapy fraction size, due to the unique radiobiological behaviour of prostate cancers in contrast with other malignancies. In this paper we discuss the rationale and the increasing body of clinical evidence for the use of this technique in patients with high-risk prostate cancer, where it is combined with external beam radiotherapy. We highlight practical aspects of delivering treatment and discuss toxicity and limitations, with particular reference to current practice in the United Kingdom.

Thromboembolic events with cisplatin-based neoadjuvant chemotherapy for transitional cell carcinoma of urinary bladder.

277 Background: Cancer is associated with an increased risk of venous and arterial thrombo-embolic events (TEEs), including deep vein thrombosis, pulmonary embolism, cerebrovascular accident and unstable angina/myocardial infarction. Several factors are known to influence the incidence of TEEs including chemotherapy agents, particularly cisplatin. Czaykowski et al reported 12.9% of patients receiving multiagent cisplatin based chemotherapy for transitional cell carcinoma between 1986 and 1996 developed TEE. Moore et al found that the rate of TEE in a similar cohort of patients receiving the same treatment to be 18.2% (6/33 patients). METHODS Retrospective case note review from an electronic database of patients allocated a cisplatin based neo-adjuvant chemotherapy regimen for transitional cell carcinoma of the bladder between April 2009 and April 2012. TEE was recorded as a chemotherapy related event if it occurred between the first dose of cisplatin and 4 weeks after the last administered dose. RESULTS 44 received treatment in the neoadjuvant setting. 11 out of 44 patients (25%) receiving neo-adjuvant chemotherapy developed TEE. 7 out of these 11 patients were male, 4 were female. 9 of the 11 TEEs (82%) in the neoadjuvant setting were arterial or peripheral arterial thrombi, including pulmonary emboli and thrombi within the aorta, left ventricle and iliac arteries. 5 of these thrombi were asymptomatic and only discovered on routine scanning. 2 out of the 11 TEEs were leg deep vein thromboses - both of which were symptomatic. 64% of TEEs occurred after the second cycle of cisplatin, the remainder after the third cycle. CONCLUSIONS Neo-adjuvant chemotherapy is being adopted as the standard of care for patients with muscle-invasive TCC of bladder. The higher rate of TEE in our series compared to previous publications probably reflects the asymptomatic TEE being diagnosed on scans done for assessing response to chemotherapy. The significant rates of TEEs in this setting highlights the need to consider this complication as it may have a bearing on outcome from treatment, in particular delay in radical cystectomy.

Radium-223 in metastatic castration resistant prostate cancer: Progression free survival and pain scores--Real-world single-institution experience.

250 Background: Radium-223 (Ra223) is a novel alpha-emitting radiopharmaceutical agent approved for use in patients with metastatic castration resistant prostate cancer (mCRPC) and bone metastases based on ALSYMPCA results. We report our early experience in this setting. Methods: 36 patients were treated with Ra223 from Feb 2014 - Aug 2015. The patients were planned to receive 6 injections at a dose of 50 kBq/kg every 4 weekly. The pain was assessed using the visual analogue score (VAS). The effect of 6 cycles of Ra223 on blood counts, serum alkaline phosphatase (SAP), PSA, VAS and progression free survival (PFS) were evaluated. Results: At baseline (BL) median age was 79years; 66% of patients were ECOG 0-1; median VAS was 6. 53% had received prior docetaxel. 18 patients (50%) received all the scheduled 6 cycles of Ra223. In these patients there was a significant reduction in the pain scores both after the first cycle and after 6 cycles compared to the BL score (p < 0.05 & p < 0.001, respectively). A 30% ...

Corrigendum to “HDR Brachytherapy in the Management of High-Risk Prostate Cancer”

[This corrects the article DOI: 10.1155/2012/980841.].