Cytotoxic chemotherapy for prostate cancer: Who and when?

2006 ◽  
Vol 7 (5) ◽  
pp. 370-377 ◽  
Author(s):  
Rebecca A. Moss ◽  
Daniel P. Petrylak
Keyword(s):  
Prostate Cancer ◽  
Cytotoxic Chemotherapy

scholarly journals Mathematical analysis and simulation study of a phase-field model of prostate cancer growth with chemotherapy and antiangiogenic therapy effects

2020 ◽  
Vol 30 (07) ◽  
pp. 1253-1295 ◽  
Author(s):  
Pierluigi Colli ◽  
Hector Gomez ◽  
Guillermo Lorenzo ◽  
Gabriela Marinoschi ◽  
Alessandro Reali ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Death ◽  
Tumor Growth ◽  
Phase Field ◽  
Clinical Studies ◽  
Advanced Prostate Cancer ◽  
Antiangiogenic Therapy ◽  
Specific Antigen ◽  
Cytotoxic Chemotherapy ◽  
Cancer Growth

Chemotherapy is a common treatment for advanced prostate cancer. The standard approach relies on cytotoxic drugs, which aim at inhibiting proliferation and promoting cell death. Advanced prostatic tumors are known to rely on angiogenesis, i.e. the growth of local microvasculature via chemical signaling produced by the tumor. Thus, several clinical studies have been investigating antiangiogenic therapy for advanced prostate cancer, either as monotherapy or in combination with standard cytotoxic protocols. However, the complex genetic alterations that originate and sustain prostate cancer growth complicate the selection of the best chemotherapeutic approach for each patient’s tumor. Here, we present a mathematical model of prostate cancer growth and chemotherapy that may enable physicians to test and design personalized chemotherapeutic protocols in silico. We use the phase-field method to describe tumor growth, which we assume to be driven by a generic nutrient following reaction–diffusion dynamics. Tumor proliferation and apoptosis (i.e. programmed cell death) can be parameterized with experimentally-determined values. Cytotoxic chemotherapy is included as a term downregulating tumor net proliferation, while antiangiogenic therapy is modeled as a reduction in intratumoral nutrient supply. An additional equation couples the tumor phase field with the production of prostate-specific antigen, which is a prostate cancer biomarker that is extensively used in the clinical management of the disease. We prove the well posedness of our model and we run a series of representative simulations leveraging an isogeometric method to explore untreated tumor growth as well as the effects of cytotoxic chemotherapy and antiangiogenic therapy, both alone and combined. Our simulations show that our model captures the growth morphologies of prostate cancer as well as common outcomes of cytotoxic and antiangiogenic mono therapy and combined therapy. Additionally, our model also reproduces the usual temporal trends in tumor volume and prostate-specific antigen evolution observed in experimental and clinical studies.

Androgen depletion and repletion as a means of potentiating the effect of cytotoxic chemotherapy in advanced prostate cancer

1987 ◽  
Vol 27 (1-3) ◽  
pp. 551-556 ◽  
Author(s):  
Andrea Manni ◽  
Richard J. Samten ◽  
Alice E. Boucher ◽  
Allan Lipton ◽  
Harold Harvey ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Advanced Prostate Cancer ◽  
Cytotoxic Chemotherapy ◽  
Androgen Depletion

Metastasis free survival in older men with nonmetastatic castration-resistant prostate cancer treated with androgen receptor inhibitors: An FDA-pooled analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 12038-12038
Author(s):  
Harpreet Singh ◽  
Lijun Zhang ◽  
Anup Amatya ◽  
Yutao Gong ◽  
Daniel L. Suzman ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Adverse Events ◽  
Older Men ◽  
Pooled Analysis ◽  
Cytotoxic Chemotherapy ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Time To Initiation

12038 Background: The FDA has approved three androgen receptor (AR) inhibitors for nonmetastatic castration-resistant prostate cancer (nmCRPC) based on improvements in metastasis-free survival (MFS). MFS is an earlier endpoint, defined as the time from randomization to either imaging-detectable distant disease or death. This pooled analysis examines MFS, time to initiation of cytotoxic chemotherapy (TTCyto), and safety outcomes in men over 80 treated with AR inhibitors. Methods: Data was pooled from three randomized controlled studies (n=4117) of AR inhibitors for nmCRPC. The treatment effect of AR inhibitors on MFS and TTCyto across age groups was evaluated using Kaplan-Meier estimates and a Cox proportional hazards regression model. Hazard Ratios for MFS and TTCyto were adjusted for baseline ECOG, total Gleason score, PSA doubling time, and prior bone-targeting therapy. Results: For patients age 80 years or older (n=675) who were treated with AR inhibitors, the hazard ratio was 0.38 (95% CI 0.29, 0.49) with an estimated median MFS of 40 months (95% CI 36, 41) versus 22 months (95% CI 18, 29) for those treated with placebo (n=348). For patients <80 (n=2019) treated with AR inhibitors, the HR was 0.31 (95% CI 0.27, 0.36) with an estimated median MFS of 41 months (95% CI 36, NR) versus 16 months (95% CI 15, 18) for those treated with placebo (n=1075). Patients over 80 also derived similar improvements in time to initiation of cytotoxic chemotherapy (HR 0.43 95% CI 0.23, 0.82), compared to their younger counterparts (HR 0.41 95% CI 0.33, 0.50). See Table for selected safety outcomes. Conclusions: In an exploratory subgroup analysis, older men (≥80) with nmCRPC derived similar benefit in MFS and time to initiation of cytotoxic chemotherapy with AR inhibitors compared with younger patients. Men age 80 and above experienced higher rates of Grade 3-4 adverse events, serious adverse events, falls, and fractures. This trend towards increased toxicity was observed regardless of treatment arm. Analysis of patient reported outcomes is ongoing. [Table: see text]

scholarly journals Optimal control of cytotoxic and antiangiogenic therapies on prostate cancer growth

2021 ◽  
pp. 1-50
Author(s):  
Pierluigi Colli ◽  
Hector Gomez ◽  
Guillermo Lorenzo ◽  
Gabriela Marinoschi ◽  
Alessandro Reali ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Optimal Control ◽  
Combined Therapy ◽  
Antiangiogenic Therapy ◽  
Cytotoxic Chemotherapy ◽  
Cancer Growth ◽  
Antiangiogenic Therapies ◽  
Control Framework ◽  
Optimal Drug ◽  
Delivery Strategies

Prostate cancer can be lethal in advanced stages, for which chemotherapy may become the only viable therapeutic option. While there is no clear clinical management strategy fitting all patients, cytotoxic chemotherapy with docetaxel is currently regarded as the gold standard. However, tumors may regain activity after treatment conclusion and become resistant to docetaxel. This situation calls for new delivery strategies and drug compounds enabling an improved therapeutic outcome. Combination of docetaxel with antiangiogenic therapy has been considered a promising strategy. Bevacizumab is the most common antiangiogenic drug, but clinical studies have not revealed a clear benefit from its combination with docetaxel. Here, we capitalize on our prior work on mathematical modeling of prostate cancer growth subjected to combined cytotoxic and antiangiogenic therapies, and propose an optimal control framework to robustly compute the drug-independent cytotoxic and antiangiogenic effects enabling an optimal therapeutic control of tumor dynamics. We describe the formulation of the optimal control problem, for which we prove the existence of at least a solution and determine the necessary first-order optimality conditions. We then present numerical algorithms based on isogeometric analysis to run a preliminary simulation study over a single cycle of combined therapy. Our results suggest that only cytotoxic chemotherapy is required to optimize therapeutic performance and we show that our framework can produce superior solutions to combined therapy with docetaxel and bevacizumab. We also illustrate how the optimal drug-naïve cytotoxic effects computed in these simulations may be successfully leveraged to guide drug production and delivery strategies by running a nonlinear least-square fit of protocols involving docetaxel and a new design drug. In the future, we believe that our optimal control framework may contribute to accelerate experimental research on chemotherapeutic drugs for advanced prostate cancer and ultimately provide a means to design and monitor its optimal delivery to patients.

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