Paclitaxel in combination with carboplatin as salvage treatment in patients with castration-resistant prostate cancer: a Hellenic oncology research group multicenter phase II study

Kentepozidis, Ν.; Soultati, Aspasia; Giassas, Stylianos; Vardakis, N.; Kalykaki, A.; Κotsakis, Athanasios; Papadimitraki, E.; Pantazopoulos, Nikolaos; Bozionellou, V.; Georgoulias, Vassilis

doi:10.1007/s00280-012-1896-9

Cited by 31 publications

(22 citation statements)

References 38 publications

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“…For metastatic adenocarcinoma of the prostate, carboplatin is used particularly for tumors with resistance to taxane monotherapy [42, 43] or for tumors exhibiting features consistent with a neuroendocrine or aggressive-variant phenotype [44, 45]. Carboplatin is typically administered in conjunction with a taxane chemotherapeutic, or with etoposide if a biopsy shows evidence of pure small cell transformation.…”

Section: Treatment Opportunities For Homologous Recombination-deficiementioning

confidence: 99%

“…Carboplatin is typically administered in conjunction with a taxane chemotherapeutic, or with etoposide if a biopsy shows evidence of pure small cell transformation. When used in an unselected population with regard to DNA repair mutation status after progression on docetaxel chemotherapy, platinum plus either docetaxel or paclitaxel produced response rates of 14–26% in prospective single-arm trials [42, 43]. General adoption of combination chemotherapy with platinum for all patients with mCRPC has been limited by lack of significant improvement in efficacy with further additive side effects of the platinum agent.…”

Section: Treatment Opportunities For Homologous Recombination-deficiementioning

confidence: 99%

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Treatment strategies for DNA repair-deficient prostate cancer

Teply

Antonarakis

2017

Expert Review of Clinical Pharmacology

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Introduction: Common recurrent genetic alterations have been identified in prostate cancer through comprehensive sequencing efforts, and the prevalence of mutations in DNA repair pathway genes in patients with advanced and metastatic disease approaches 20–25%. Identification of these underlying DNA repair defects may present unique treatment opportunities for patients, both in terms of standard-of-care treatments and selected investigational agents. Areas Covered: We review our current understanding of the genomic landscape of prostate cancer, with special attention to alterations in DNA repair pathway genes in metastatic castration-resistant disease. For patients with tumors deficient in homologous recombination repair, potential opportunities for treatment include platinum chemotherapy, poly(ADP) ribose polymerase (PARP) inhibitors, bipolar androgen therapy, and maybe immune checkpoint blockade therapy. In addition, tumors with mismatch repair defects (i.e. microsatellite instability) may be particularly susceptible to checkpoint blockade immunotherapy. Expert Commentary: We anticipate that genomic profiling of tumors will become necessary to guide treatment of advanced prostate cancer treatment in the coming years. Work is needed to define the optimal tissue to test, and to define the national history of tumors with specific genetic defects. The prognostic and therapeutic importance of germline vs somatic DNA repair alterations, and mono-allelic vs bi-allelic inactivation, also remains unclear. Finally, optimal strategies to sequence or combine targeted agents for these patients with ‘actionable’ mutations are now needed.

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Section: Treatment Opportunities For Homologous Recombination-deficiementioning

confidence: 99%

Section: Treatment Opportunities For Homologous Recombination-deficiementioning

confidence: 99%

Treatment strategies for DNA repair-deficient prostate cancer

Teply

Antonarakis

2017

Expert Review of Clinical Pharmacology

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“…Paclitaxel chemotherapy combined with prednisone can not only effectively improve the clinical symptoms of prostate cancer but also relieve pain, thereby prolonging the survival time of patients. For these reasons, it has become the rst choice for the treatment of hormoneindependent prostate cancer [28]. However, akin to chemotherapy for other cancers, prostate cancer chemotherapy also poses problems such as toxicity and side effects on the liver, heart and kidney, being unamenable to monitoring in real-time if the drug reaches the target organ, and di culty in locally concentrating the chemotherapeutic agents.…”

Section: Discussionmentioning

confidence: 99%

Multifunctional Nanobubbles Carrying Indocyanine Green and Paclitaxel for Molecular Imaging and the Treatment of Prostate Cancer

Lan

Zhu

Wang

et al. 2020

Preprint

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Background: Combining ultrasound imaging with photoacoustic imaging provides tissue imaging with high contrast and resolution, thereby enabling rapid, direct measurements and the tracking of tumour growth and metastasis. Moreover, ultrasound-targeted nanobubble destruction (UTND) provides an effective way to deliver drugs, effectively increasing the content of the drug in the tumour area and reducing potential side effects, thereby successfully contributing to the treatment of tumours. Results: In this study, we prepared multifunctional nanobubbles (NBs) carrying indocyanine green (ICG) and paclitaxel (PTX) (ICG-PTX NBs) and studied their applications in ultrasound imaging of prostate cancer as well as their therapeutic effects on prostate cancer when combined with UTND. ICG-PTX NBs were prepared by the mechanical oscillation method. The particle size and zeta potential of the ICG-PTX NBs were 469.5 ± 32.87 nm and -21.70 ± 1.22 mV, respectively. The encapsulation efficiency and drug loading efficiency of ICG were 68% and 6.2%, respectively. In vitro imaging experiments showed that ICG-PTX NBs were highly amenable to multimodal imaging, including ultrasound, photoacoustic and fluorescence imaging, and the imaging effect was positively correlated with their concentration. The imaging effects of tumour xenografts also indicated that ICG-PTX NBs were of good use for multimodal imaging. In experiments testing the growth of PC-3 cells in vitro and tumour xenografts in vivo, the ICG-PTX NBs+US group showed more significant inhibition of cell proliferation and the promotion of cell apoptosis compared to the other groups (P < 0.05). Blood biochemical analysis of the six groups showed that the levels of aspartate aminotransferase (AST), phenylalanine aminotransferase (ALT), serum creatinine (CRE) and blood urea nitrogen (BUN) in the ICG-PTX NBs and the ICG-PTX NBs+US groups were significantly lower than those in the PTX group (P < 0.05). Moreover, H&E staining of tissue sections from vital organs showed no obvious abnormalities in the ICG-PTX NBs and the ICG-PTX NBs+US groups. Conclusions: ICG-PTX NBs can be used as a non-invasive, pro-apoptotic contrast agent that can achieve multimodal imaging, including ultrasound, fluorescence and photoacoustic imaging, and can succeed in the local treatment of prostate cancer providing a potential novel method for integrated research on prostate cancer diagnosis and treatment.

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“…So far, few cases of dramatic and sustained response to carboplatin/cisplatin therapy have been recently reported. All cases harbored a biallelic inactivation of the BRCA2 gene [32,33]. Multiple trials are now testing platinum-based chemotherapy in PCa patients with HRR mutations.…”

Section: Parp Inhibitorsmentioning

confidence: 99%

Germline and Somatic Mutations in Prostate Cancer: Focus on Defective DNA Repair, PARP Inhibitors and Immunotherapy

et al. 2020

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Paclitaxel in combination with carboplatin as salvage treatment in patients with castration-resistant prostate cancer: a Hellenic oncology research group multicenter phase II study

Abstract: The biweekly administration of paclitaxel/carboplatin regimen in patients with castration-resistant prostate cancer is an active and well-tolerated regimen which merits to be further evaluated in the context of salvage treatment.

Cited by 31 publications

References 38 publications

Treatment strategies for DNA repair-deficient prostate cancer

Treatment strategies for DNA repair-deficient prostate cancer

Multifunctional Nanobubbles Carrying Indocyanine Green and Paclitaxel for Molecular Imaging and the Treatment of Prostate Cancer

Germline and Somatic Mutations in Prostate Cancer: Focus on Defective DNA Repair, PARP Inhibitors and Immunotherapy

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