Evolving Landscape and Novel Treatments in Metastatic Castrate-Resistant Prostate Cancer

Treatment options for castrate-resistant prostate cancer (CRPC) have advanced in recent years and significantly improved the outlook for patients with this aggressive and lethal disease. Further understanding of the biology of CRPC has led to several new targeted therapies and continues to emphasize the importance of androgen receptor (AR) directed therapy. The treatment landscape is rapidly changing and further biologically rationale, biomarker-based ongoing clinical trials are needed. We review the recent results of major clinical trials in CRPC…”

Overcoming mutation-based resistance to antiandrogens with rational drug design

The second-generation antiandrogen enzalutamide was recently approved for patients with castration-resistant prostate cancer. Despite its success, the duration of response is often limited. For previous antiandrogens, one mechanism of resistance is mutation of the androgen receptor (AR). To prospectively identify AR mutations that might confer resistance to enzalutamide, we performed a reporter-based mutagenesis screen and identified a novel mutation, F876L, which converted enzalutamide into an AR agonist…”

Phase III, Randomized, Placebo-Controlled Study of Docetaxel in Combination With Zibotentan in Patients With Metastatic Castration-Resistant Prostate Cancer

“As part of the ENTHUSE (Endothelin A Use) program, the efficacy and safety of zibotentan (ZD4054), an oral specific endothelin A receptor antagonist, has been investigated in combination with docetaxel in patients with metastatic castration-resistant prostate cancer (CRPC)…”

Antitumour activity of abiraterone acetate against metastatic castration-resistant prostate cancer progressing after docetaxel and enzalutamide (MDV3100)

Background: Androgen receptor (AR) signalling remains critically important in metastatic castration-resistant prostate cancer (mCRPC) as confirmed by recent phase III trials, showing a survival advantage for abiraterone acetate and enzalutamide (MDV3100). The antitumour activity of abiraterone and prednisolone in patients pre-treated with enzalutamide is as yet unknown. Patients and methods: We investigated the antitumour activity of abiraterone and prednisolone in patients with mCRPC who had progressed following treatment with docetaxel (Taxotere) and enzalutamide…”

TAK-441, a novel investigational smoothened antagonist, delays castration resistant progression in prostate cancer by disrupting paracrine hedgehog signaling

Hedgehog (Hh) signaling is a highly conserved inter- and intracellular communication mechanism that governs organogenesis and is dysregulated in cancers of numerous tissues, including prostate. Up-regulated expression of the Hh ligands, Sonic (Shh) and Desert (Dhh), has been reported in androgen-deprived and castration-resistant prostate cancer (CRPC). In a cohort of therapy naive, short- and long-term neoadjuvant hormone therapy-treated (NHT), and CRPC specimens, we observed…”

Intermittent versus Continuous Androgen Deprivation in Prostate Cancer

“Castration resistance occurs in most patients with metastatic hormone-sensitive prostate cancer who are receiving androgen-deprivation therapy. Replacing androgens before progression of the disease is hypothesized to prolong androgen dependence…”

Melanoma Drug Completes Clinical Trial for Treating Metastatic CRPC

Ipilimumab, a drug used to treat melanoma, is being studied alone and in combination with radiation therapy for treating metastatic castration-resistant prostate cancer (CRPC). The drug, which works by activating the body’s immune system to attack and destroy prostate cancer cells, has completed a phase I/II clinical trial involving 33 patients. Eight patients had more than a 50% decrease in their prostate-specific antigen (PSA) blood levels, one had a complete response to treatment, and six had stable disease for 2.8 to 6.1 months. Most patients had manageable adverse side effects. Two phase III clinical trials are ongoing.

Ipilimumab alone or in combination with radiotherapy in metastatic castration-resistant prostate cancer: results from an open-label, multicenter phase I/II study

Background: This phase I/II study in patients with metastatic castration-resistant prostate cancer (mCRPC) explored ipilimumab as monotherapy and in combination with radiotherapy, based on the preclinical evidence of synergistic antitumor activity between anti-CTLA-4 antibody and radiotherapy. Patients and methods: In dose escalation, 33 patients (≥6/cohort) received ipilimumab every 3 weeks × 4 doses at 3, 5, or 10 mg/kg or at 3 or 10 mg/kg + radiotherapy (8 Gy/lesion)…”

New Cancer Vaccine Enters Phase IIb Clinical Trial for Patients with CRPC

CureVac, a German biopharmaceutical company, announced the start of a phase IIb clinical trial of its vaccine, CV9104, for castration-resistant prostate cancer (CRPC). The vaccine works by prompting the body’s own immune system to attack prostate cancer cells. The trial will enroll up to 200 patients across eight European countries who have never received chemotherapy for CRPC. For more information on the clinical trial click here.