Uncommon Cancers of the Prostate

Tagawa, Scott T.; Akhtar, Naveed; Robinson, Brian D.; Beltran, Himisha

doi:10.1002/9781118464557.ch4

Cited by 5 publications

(1 citation statement)

References 316 publications

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“…Although a uniform definition of this clinical entity has yet to be adopted, NEPC shares histologic features with small-cell carcinomas, makes little or no PSA in relationship to tumor burden, and gives rise to more visceral and lytic bone-metastases rather than the traditional pattern of soft tissue bone-metastasis and lymph node involvement seen with prostatic adenocarcinomas [48][49][50][51][52][53][54]. Due to its clinical and histologic similarity to small-carcinoma of the lung, platinum containing chemotherapy combinations are often used to treat patients with NEPC [54][55][56][57][58][59].…”

Section: Chemotherapy For Neuroendocrine Pcmentioning

confidence: 98%

The Evolving Role of Cytotoxic Chemotherapy in the Management of Patients with Metastatic Prostate Cancer

Diamond

Garcias

Karir

et al. 2015

Curr. Treat. Options in Oncol.

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Section: Chemotherapy For Neuroendocrine Pcmentioning

confidence: 98%

The Evolving Role of Cytotoxic Chemotherapy in the Management of Patients with Metastatic Prostate Cancer

Diamond

Garcias

Karir

et al. 2015

Curr. Treat. Options in Oncol.

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Abiraterone plus prednisone improves survival in metastatic castration-resistant prostate cancer

Tagawa¹,

Beltran²

2011

Asian J Androl

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Randomized phase II study of danusertib in patients with metastatic castration‐resistant prostate cancer after docetaxel failure

et al. 2012

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NCT00766324What's known on the subject? and What does the study add?• Since their discovery aurora kinases have been identified as a potential target in anticancer therapy and currently many aurora-selective small molecule kinase inhibitors are in development. Aurora kinases play an essential role as key mitotic regulators and are frequently overexpressed in prostate cancer. In vivo data in the transgenic mouse prostate carcinoma model revealed tumour regressions of >80% in three out of 16 animals and disease stabilizations in 10 out of 16 animals treated with danusertib. Two phase I dose escalation studies with danusertib in patients with advanced solid tumours were performed, which established two doses and schedules for phase II studies. However, the preliminary data of the available phase II studies with danusertib in solid tumours showed limited activity. Danusertib may yield more activity in the treatment of leukaemias than in solid tumours. Danusertib is generally well tolerated with neutropenia as the main dose limiting toxicity.• This phase II study determined the efficacy and toxicity of danusertib administered intravenously over two different dosing schedules in patients with metastatic castration-resistant prostate cancer (CRPC) with progressive disease after docetaxel-based treatment. Danusertib showed in vivo antitumour activity in prostate cancer models and clinically relevant disease stabilizations were observed in several patients with solid tumours in phase I studies. However, our study revealed that monotherapy with danusertib, although well tolerated, showed only limited activity in the treatment of patients with CRPC. In view of the new advances in the treatment of patients with CRPC and the negative result of our study it is unlikely that danusertib will be further explored for the treatment of patients with CRPC. Further studies are required to establish specific biomarkers predictive for either response or prolonged disease stabilization to select subsets of patients with CRPC who may benefit from treatment with danusertib. Objective• To determine the efficacy and toxicity of danusertib (formerly PHA-739358) administered i.v. over two different dosing schedules with equivalent dose intensity in patients with metastatic castration-resistant prostate cancer with progressive disease after docetaxel-based treatment. Patients and Methods• In this open-label, multicentre phase II trial 88 patients were randomly assigned (1:1 ratio) to receive either danusertib 330 mg/m 2 over 6 h i.v. on days 1, 8 and 15 (arm A, n = 43) or 500 mg/m 2 over 24 h i.v. on days 1 and 15 (arm B, n = 38), every 4 weeks.• The primary endpoint chosen for this exploratory study was PSA response rate at 3 months. Results• Sixty patients (31/43 in arm A and 29/38 in arm B) were evaluable for the primary endpoint.• Median progression-free survival was 12 weeks in both arms.

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Uncommon Cancers of the Prostate

Cited by 5 publications

References 316 publications

The Evolving Role of Cytotoxic Chemotherapy in the Management of Patients with Metastatic Prostate Cancer

The Evolving Role of Cytotoxic Chemotherapy in the Management of Patients with Metastatic Prostate Cancer

Abiraterone plus prednisone improves survival in metastatic castration-resistant prostate cancer

Randomized phase II study of danusertib in patients with metastatic castration‐resistant prostate cancer after docetaxel failure

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