scholarly journals SEOM clinical guidelines for the treatment of advanced prostate cancer (2020)

2021 ◽  
Author(s):  
A. González del Alba ◽  
M. J. Méndez-Vidal ◽  
S. Vazquez ◽  
E. Castro ◽  
M. A. Climent ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Advanced Prostate Cancer ◽  
Therapeutic Strategy ◽  
High Volume ◽  
Brca1 And Brca2 ◽  
Castration Resistant ◽  
Platinum Based Chemotherapy ◽  
Brca1 Brca2 ◽  
Repair Genes ◽  
Selection Of

AbstractThe treatment of advanced prostate cancer has evolved due to recent advances in molecular research and new drug development. Dynamic aberrations in the androgen receptor, DNA repair genes, PTEN-PI3K, and other pathways drive the behavior of advanced prostate cancer allowing a better selection of therapies in each patient. Tumor testing for BRCA1 and BRCA2 is recommended for patients with metastatic prostate cancer, also considering a broad panel to guide decisions and genetic counseling. In symptomatic metastatic patients, castration should be stared to palliate symptoms and prolong survival. In high-risk or high-volume metastatic hormone-naïve patients, castration should be combined with docetaxel, abiraterone, enzalutamide or apalutamide. Radiotherapy to the primary tumor combined with systemic therapy is recommended in low-volume mHNPC patients. In patients with non-metastatic castration-resistant tumors, risk stratification can define the frequency of imaging. Adding enzalutamide, darolutamide or apalutamide to these patients prolongs metastasis-free and overall survival, but potential adverse events need to be taken into consideration. The choice of docetaxel, abiraterone or enzalutamide for treating metastatic castration-resistant patients depends on previous therapies, with cabazitaxel being also recommended after docetaxel. Olaparib is recommended in BRCA1/BRCA2 mutated castration-resistant patients after progression on at least one new hormonal therapy. Aggressive variants of prostate cancer respond to platinum-based chemotherapy. To optimize treatment efficiency, oncologists should incorporate all of these advances into an overall therapeutic strategy.

Platinum-based chemotherapy in metastatic prostate cancer with alterations in DNA damage repair genes.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5038-5038
Author(s):  
Jose Mauricio Mota ◽  
Ethan Barnett ◽  
Jones Nauseef ◽  
Konrad Hermann Stopsack ◽  
Andreas Georg Wibmer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Damage ◽  
Parp Inhibitor ◽  
Dna Damage Repair ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Damage Repair ◽  
Platinum Based Chemotherapy ◽  
Before And After ◽  
Repair Genes

5038 Background: Platinum-based chemotherapy has shown palliative and radiographic benefit in small unselected studies of metastatic castration-resistant prostate cancer (mCRPC). Alterations in DNA damage repair genes (DDRmut), which occur in ~25% of patients with mCRPC, may sensitize to platinum-based chemotherapy, and may aid in the selection of patients for this therapy. We sought to evaluate the efficacy of platinum-based chemotherapy in DDRmut mCRPC. Methods: We performed a retrospective review of patients with prostate cancer who underwent tumor genomic profiling and received platinum-based chemotherapy. Deleterious alterations in a panel including BRCA2, BRCA1, ATM, FANCA, CDK12 or PALB2 were classified as DDRmut. Absence of deleterious alterations in those genes was classified as DDRwt. MSI-H cases were excluded from analysis. Electronic charts, PSA values, and scans were reviewed to assess for outcomes. Results: From October 2013 to July 2018, 109 patients with mCRPC received platinum-based chemotherapy. 64/109 had prior taxane progression and were PARP inhibitor (PARPi) naïve at the time of platinum-based chemotherapy. DDRmut was found in 16/64 (25%) of patients ( BRCA2, n = 6; ATM, n = 2; CDK12, n = 4; FANCA, n = 4; PALB2, n = 1). Visceral metastasis occurred in 4/16 (25%) of DDRmut patients and in 22/48 (46%) of DDRwt patients. PSA50 responses were more common among DDRmut (8/15 evaluable = 53%, 95% CI, 30-75%) than among DDRwt patients (5/42 evaluable = 12%, 95% CI, 5-25%). Time on platinum-based chemotherapy tended to be longer in the DDRmut group (median 3.1 vs 1.8 months; HR 0.73, 95% CI 0.42-1.26). Of 8 DDRmut patients ( BRCA2, n = 6; BRCA1, n = 1; ATM, n = 2) who received platinum-based chemotherapy after progression on a PARPi, 3/7 evaluable patients (43%) had RECIST response or stable disease, and 2/7 evaluable patients (29%) had a PSA50 response. Of 4 patients with ATM deleterious mutations, none had a radiographic or PSA50 response to platinum-based chemotherapy. Conclusions: Platinum-based chemotherapy showed activity in DDRmut mCRPC patients before and after PARPi treatment.

Emerging Biomarkers and Contributing Factors of Prostate Cancer.

2020 ◽  
Vol 16 ◽  
Author(s):  
Mini Dahiya ◽  
Monu Yadav ◽  
Kalpana Nagpal ◽  
Nidhi Sharma ◽  
Kajal Joshi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Prostate Cancer ◽  
Tumor Suppressor Genes ◽  
Therapeutic Strategy ◽  
Cannabinoid Receptors ◽  
Contributing Factors ◽  
Cause Of Deaths ◽  
Pharmaceutical Industries ◽  
Brca1 Brca2 ◽  
Molecular Pathophysiology

: Prostate Cancer (PC) is one the most prominent cause of deaths in males worldwide especially in western countries. The exhaustive research into prostate cancer to date has demonstrated ELAC2, RNASEL, MSR1, NBS1, CHEK2, MYC, BCL-2, c-Kit, tumor suppressor genes, BRCA1, BRCA2, PACE4, GSTP1, PTEN,CDKN1B, NKX3.1, KLF6, FOXA1, Retinoblastoma, p53, androgen receptor, kallikreins, ETS, CYP17, SRD5A2, E-cadherin, KAI1/CD82, hepsin, AMACR, PIM1, MTA-1, EZH2, EPHB2, growth factors & its receptors, cannabinoid receptors, annexins, oxidative stress and inflammation are entailed changes underlying the initiation, development, and progression of PC. Furthermore, oncology would shift from a reactive to proactive discipline so exploring these targets open new area of research. Therefore, the present review is focused on molecular pathophysiology biomarkers for the progression of PC that would encourage the researchers and pharmaceutical industries to investigate potential therapeutic strategy to overcome demerits of currently available clinically therapies.

scholarly journals Changing the History of Prostate Cancer with New Targeted Therapies

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 392
Author(s):  
Susana Hernando Polo ◽  
Diana Moreno Muñoz ◽  
Adriana Carolina Rosero Rodríguez ◽  
Jorge Silva Ruiz ◽  
Diana Isabel Rosero Rodríguez ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Targeted Therapies ◽  
Synthetic Lethality ◽  
Castration Resistant Prostate Cancer ◽  
Phosphatidylinositol 3 Kinase ◽  
Castration Resistant ◽  
Therapeutic Landscape ◽  
Important Benefit ◽  
History Of ◽  
Repair Genes

The therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) is changing due to the emergence of new targeted therapies for the treatment of different molecular subtypes. Some biomarkers are described as potential molecular targets different from classic androgen receptors (AR). Approximately 20–25% of mCRPCs have somatic or germline alterations in DNA repair genes involved in homologous recombination. These subtypes are usually associated with more aggressive disease. Inhibitors of the enzyme poly ADP ribose polymerase (PARPi) have demonstrated an important benefit in the treatment of these subtypes of tumors. However, tumors that resistant to PARPi and wildtype BRCA tumors do not benefit from these therapies. Recent studies are exploring drug combinations with phosphatidylinositol-3-kinase (PI3K) or protein kinase B (AKT) inhibitors, as mechanisms to overcome resistance or to induce BRCAness and synthetic lethality. This article reviews various different novel strategies to improve outcomes in patients with prostate cancer.

scholarly journals Targeting TCTP as a New Therapeutic Strategy in Castration-resistant Prostate Cancer

2012 ◽  
Vol 20 (12) ◽  
pp. 2244-2256 ◽  
Author(s):  
Virginie Baylot ◽  
Maria Katsogiannou ◽  
Claudia Andrieu ◽  
David Taieb ◽  
Julie Acunzo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Therapeutic Strategy ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

Salvage chemotherapy with cisplatin, ifosfamide, and paclitaxel in metastatic castration-resistant prostate cancer.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 123-123
Author(s):  
Gunhild Von Amsberg ◽  
Mirjam Zilles ◽  
Philipp Gild ◽  
Winfried Alsdorf ◽  
Lukas Boeckelmann ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Synergistic Effects ◽  
Antagonistic Effect ◽  
University Hospital ◽  
Additive Effects ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Platinum Based Chemotherapy ◽  
Wide Range

123 Background: Recent developments in the treatment of metastatic castration resistant prostate cancer (mCRPC) lead to a revival of platinum-based chemotherapy demonstrating increased activity in patients with aggressive variants of disease. Here, we report on the results of a combinational salvage therapy with cisplatin, ifosfamide and paclitaxel (TIP) in mCRPC. Methods: We retrospectively analyzed patients with mCRPC treated with TIP at the University Hospital Hamburg-Eppendorf between November 2013 and September 2020. Accompanying in vitro analyses were performed using human prostate carcinoma cell lines harboring different levels of drug resistance including the docetaxel-resistant sublines PC3-DR and DU45-DR. Results: In total, 17 mCRPC patients treated with TIP were eligible for efficacy analyses with a median age of 65 yrs. At baseline, liver metastases were present in 88%, metastases of other visceral sides (lung, adrenal gland, brain) in 47% and bone metastases in 76% of the patients. Median hemoglobin was 9.8mg/dl, LDH 903 U/l and AP 205 U/l. Median PSA value was 77 ng/ml covering a wide range including three patients with a PSA-value below 1ng/ml. NSE was evaluated in 83% of the patients (median 38,5 U/l). Patients were extensively pretreated with a median of three treatment lines before TIP (100% docetaxel, 82% abirateron and/or enzalutamide, 47% cabazitaxel, 41% others). A median of 3,5 cycles of TIP were applied with 29% of the patients receiving the maximum of 6 cycles. Four patients discontinued treatment due to side effects (PNP, infection, ifosfamide induced psychosis). At interim analyses, 59 % of the patients showed a radiological response or stable disease with only one patient progressing till the end of treatment. Median PFS was 2.5 months, median OS 6 months. A decrease of PSA > 30% and LDH > 50% was observed in 41% and 35% of the patients, respectively. In vitro experiments revealed additive effects of TIP in 22Rv1, LNCaP and DU45 cells and synergistic effects in neuroendocrine LASCPC-01 cells. In PC3 cells, TIP induced antagonistic effects at lower doses, whereas dose-independent additive effects were observed in docetaxel-resistant PC3-DR. Surprisingly, preliminary data of combined therapies with different drug pairs suggest an antagonistic effect of paclitaxel in the combination with both, cisplatin and ifosfamide. Conclusions: Combinational therapy with cisplatin, ifosfamide and paclitaxel showed promising activity in some patients with aggressive mCRPC. Preclinical data suggest that the drug combination of cisplatin and ifosfamide rule the efficacy of TIP in mCRPC.

scholarly journals A A Canadian consensus forum on the management of patients with advanced prostate cancer

2019 ◽  
Vol 14 (4) ◽  
Author(s):  
Fred Saad ◽  
Christina Canil ◽  
Antonio Finelli ◽  
Sebastien J. Hotte ◽  
Shawn Malone ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Advanced Prostate Cancer ◽  
Castration Resistant Prostate Cancer ◽  
Research Education ◽  
Modified Delphi ◽  
Castration Resistant ◽  
Medical Oncologists ◽  
Oligometastatic Prostate Cancer ◽  
Scientific Group ◽  
High Level

Introduction: The management of advanced prostate cancer (PCa) continues to evolve with the emergence of new diagnostic and therapeutic strategies. As a result, there are multiple areas in this landscape with a lack of high-level evidence to guide practice. Consensus initiatives are an approach to establishing practice guidance in areas where evidence is unclear. We conducted a Canadian-based consensus forum to address key controversial areas in the management of advanced PCa. Methods: As part of a modified Delphi process, a core scientific group of PCa physicians (n=8) identified controversial areas for discussion and developed an initial set of questions, which were then reviewed and finalized with a larger group of 29 multidisciplinary PCa specialists. The main areas of focus were non-metastatic castration-resistant prostate cancer (nmCRPC), metastatic castration-sensitive prostate cancer (mCSPC), metastatic castration-resistant prostate cancer (mCRPC), oligometastatic prostate cancer, genetic testing in prostate cancer, and imaging in advanced prostate cancer. The predetermined threshold for consensus was set at 74% (agreement from 20 of 27 participating physicians). Results: Consensus participants included uro-oncologists (n=13), medical oncologists (n=10), and radiation oncologists (n=4). Of the 64 questions, consensus was reached in 30 questions (n=5 unanimously). Consensus was more common for questions related to biochemical recurrence, sequencing of therapies, and mCRPC. Conclusions: A Canadian consensus forum in PCa identified areas of agreement in nearly 50% of questions discussed. Areas of variability may represent opportunities for further research, education, and sharing of best practices. These findings reinforce the value of multidisciplinary consensus initiatives to optimize patient care.

scholarly journals Effect of DNA damage response mutations on prostate cancer prognosis: a systematic review

2019 ◽  
Vol 15 (28) ◽  
pp. 3283-3303 ◽  
Author(s):  
Stephanie L Swift ◽  
Shona H Lang ◽  
Heath White ◽  
Kate Misso ◽  
Jos Kleijnen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Dna Damage ◽  
Clinical Outcomes ◽  
Dna Damage Response ◽  
Parp Inhibitor ◽  
Cancer Prognosis ◽  
Castration Resistant ◽  
Damage Response ◽  
Brca1 Brca2

The prognosis of men with prostate cancer (PC) with mutations in DNA damage response ( DDR) genes undergoing different treatments is unclear. This systematic review compared clinical outcomes in PC patients with DDR mutations ( DDR+) versus no mutations ( DDR-). 14 resources plus gray literature were searched for studies in PC and subgroups (castration-resistant PC, metastatic PC and metastatic castration-resistant PC) by DDR gene ( ATM, ATR, BRCA1, BRCA2, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, RAD51C) mutation status. From 11,648 records, 26 studies were included. For mCRPC, six studies reported comparative efficacy for key outcomes. Improvements in several clinical outcomes were observed for DDR+ (vs DDR-) after PARP inhibitor therapy or immunotherapy. DDR+ PC patients may have improved outcomes depending on the treatment they undergo.

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