Search

What's known on the subject? and What does the study add? Recent advances in the treatment of metastatic castration-resistant prostate cancer ( CRPC) have resulted in improved outcomes; however, the effects have not proved to be long term, highlighting the need for new therapies, particularly in patients with docetaxel-refractory metastatic CRPC. Angiogenesis has been shown to play an important role in the development and progression of prostate cancer. Although targeting angiogenesis appears to be a rational and therapeutic approach for metastatic CRPC, identifying the appropriate subgroups that may benefit from anti-angiogenic therapy remains a challenge., The study demonstrates the potential use of dynamic contrast-enhanced ( DCE)- MRI variables as pharmacodynamic endpoints in predicting the clinical outcomes associated with anti-angiogenic agents such as cediranib. Further investigation into the potential predictive value of DCE-MRI variables as biomarkers for antiangiogenic therapy is warranted., Objective To assess the efficacy and toxicity of cediranib, a highly potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, in patients with metastatic castration-resistant prostate cancer ( CRPC) previously treated with docetaxel-based therapy., Patients and Methods The study used a Simon two-stage trial design, which required at least two of 12 patients in the first cohort to be progression-free at 6 months., We enrolled a total of 35 evaluable patients who all received cediranib 20 mg orally daily., In a second cohort, 23 additional patients received prednisone 10 mg daily with cediranib., Endpoints included tumour response, progression-free survival ( PFS), overall survival ( OS), vascular permeability via dynamic contrast-enhanced magnetic resonance imaging ( DCE-MRI), and toxicity., Results A total of 59 patients were enrolled, of whom 67% had received two or more previous chemotherapy regimens., Six of 39 patients with measurable disease had confirmed partial responses and one had an unconfirmed partial response., At 6 months, 43.9% of patients were progression-free; the median PFS and OS periods for all patients were 3.7 months and 10.1 months, respectively., We found that the DCE-MRI variables baseline transport constant ( Ktrans) and rate constant at day 28 were significantly associated with PFS in univariate analyses, but only baseline Ktrans remained significant when considered jointly., The most frequent toxicities were hypertension, fatigue, anorexia and weight loss; the addition of prednisone reduced the incidence of constitutional toxicities., Conclusion This study demonstrated that cediranib was generally well tolerated with some anti-tumour activity in highly pretreated patients with metastatic CRPC who had progressive disease after docetaxel-based therapy. [ABSTRACT FROM AUTHOR]

Objectives of this study were to determine the maximum tolerated dose and to characterize the side effect profile and pharmacokinetics of lenalidomide in patients with advanced refractory solid tumors. Patients were treated on a modified Fibronacci dose escalation scheme with an oral daily dose of lenalidomide. A total of 45 patients with 8 different tumor types were accrued. Doses administered included 5, 10, and 20 mg continuous daily doses, every 28 days (n = 15), later modified to intermittent doses of 15, 20, 25, 30, 35, and 40 mg, with a 21 days-on and 7 days-off schedule, due to observed side effects. Lenalidomide exhibited a linear pharmacokinetics over a wide range of doses with the mean half-life of 3.9 hours. The renal function affected lenalidomide clearance, resulting in 50% reduction in patients with mild renal impairment compared with patients with normal function (CL/F = 243 mL/min). Stable disease was documented in 12 of 44 evalu-able patients, of whom 9 patients had prostate cancer. Most frequent grade 1 and 2 toxicities included fatigue, nausea, pruritus/rash, neutropenia, and neuropathy. Grade 3/4 events were predominantly hematologic. Lenalidomide was well tolerated up to a 35-mg/d intermittent dosing schedule at doses higher than previously indicated for hematologic malignancies. [ABSTRACT FROM AUTHOR]

Authors from the National Cancer Institute present a study which assessed the time to androgen independence and overall survival for patients with metastatic prostate cancer. They reported a longer than expected survival with androgen-independent prostate cancer, and make original observations on the time to metastatic disease for patients with no evidence of radiographic disease. The new wave of chemotherapeutic agents for hormone-resistant prostate cancer has generated a new interest in producing more. Dr Cora Sternberg from Rome presents information on satraplatin, a third-generation orally available platinum analogue that shares more structural similarities with cisplatin. There are several other papers in this section on prostate bladder and renal cancer, and finally a paper from London on penile cancer, asking what surgical resection margins are required to achieve oncological control, and finding that the traditional 2 cm margin may be unnecessary, with excision margins of only a few millimetres needed to give excellent control. OBJECTIVE To determine the natural history of patients with prostate cancer who start initial androgen-deprivation therapy (ADT) for biochemical failure with no radiographic evidence of disease (D0) or with radiographic metastatic disease (D2), as the history is either not well-defined or is changing, and such data are critical for guiding therapy after prostate cancer recurrence. PATIENTS AND METHODS We retrospectively assessed the time to androgen-independence (AI), defined as the first sustained rise in prostate-specific antigen (PSA) level on ADT, time to metastatic disease and overall survival for 80 patients with metastatic prostate cancer in clinical trials at the National Cancer Institute. RESULTS ADT was initiated after metastatic disease in 37 patients and before metastatic disease in 43 patients; in these 43 patients, the median time to developing metastatic disease on ADT was 37.8 months. The median time to AI from the initiation of ADT was 19.3 and 13.1 months in D0 and D2 patients, respectively. The median overall survival from the start of ADT was 89.0 and 63.0 months, and the median overall survival from the time of AI was 63.1 and 44.2 months in D0 and D2 patients, respectively. These 80 patients, which included 43 who had no metastatic disease when starting ADT, had a median survival of 54.8 months after AI prostate cancer. CONCLUSIONS We describe the natural history of AI prostate cancer in D0 patients who eventually developed metastasis, and in D2 patients. The results suggest a longer than expected survival with AI prostate cancer, and to our knowledge this is the first study to report the time to metastatic disease for D0 patients from ADT and from AI. These results can be used to help design clinical trials in patients with D0 prostate cancer. [ABSTRACT FROM AUTHOR]