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past decade has witnessed a host of technologic improvements in prostate cancer therapy. The three major modalities offered in most managed care plans include radical prostatectomy, external-beam radiation therapy (EBRT), and interstitial brachytherapy (seed implant). Continued technologic advancement has led to incremental improvements in the safety and effectiveness of each modality. However, these improvements have led to a significant increase in the cost of treatment.
Preliminary phase I trial data suggest that the combination of recombinant IL-21 and sorafenib (Nexavar) is well tolerated in patients with metastatic renal cell carcinoma and has promising anti-tumor activity, lead investigator John A. Thompson, MD, and his colleagues reported
Rising prostate-specific antigen (PSA) in nonmetastatic prostate cancer occurs in two main clinical settings: (1) rising PSA to signal failed initial local therapy and (2) rising PSA in the setting of early hormone-refractory prostate cancer prior to documented clinical metastases. Most urologists and radiation oncologists are very familiar with the initial very common clinical scenario, commonly called "biochemical recurrence." In fact, up to 70,000 men each year will have a PSA-only recurrence after failed definitive therapy. The ideal salvage therapy for these men is not clear and includes salvage local therapies and systemic approaches, of which the mainstay is hormonal therapy. Treatment needs to be individualized based upon the patient's risk of progression and the likelihood of success and the risks involved with the therapy. It is unknown how many men per year progress with rising PSA while on hormonal therapy without documented metastases. This rising PSA disease state is sometimes called, "PSA-only hormone-refractory prostate cancer." As in the setting of initial biochemical recurrence, evidence-based treatment options are limited, and taking a risk-stratified approach is justified. In this article, we will explore these prostate cancer disease states with an emphasis on practical, clinically applicable approaches.
Rising prostate-specific antigen (PSA) in nonmetastatic prostate cancer occurs in two main clinical settings: (1) rising PSA to signal failed initial local therapy and (2) rising PSA in the setting of early hormone-refractory prostate cancer prior to documented clinical metastases. Most urologists and radiation oncologists are very familiar with the initial very common clinical scenario, commonly called "biochemical recurrence." In fact, up to 70,000 men each year will have a PSA-only recurrence after failed definitive therapy. The ideal salvage therapy for these men is not clear and includes salvage local therapies and systemic approaches, of which the mainstay is hormonal therapy. Treatment needs to be individualized based upon the patient's risk of progression and the likelihood of success and the risks involved with the therapy. It is unknown how many men per year progress with rising PSA while on hormonal therapy without documented metastases. This rising PSA disease state is sometimes called, "PSA-only hormone-refractory prostate cancer." As in the setting of initial biochemical recurrence, evidence-based treatment options are limited, and taking a risk-stratified approach is justified. In this article, we will explore these prostate cancer disease states with an emphasis on practical, clinically applicable approaches.
Sunitinib lowers PSA in some advanced prostate cancer pts
Rising prostate-specific antigen (PSA) in nonmetastatic prostate cancer occurs in two main clinical settings: (1) rising PSA to signal failed initial local therapy and (2) rising PSA in the setting of early hormone-refractory prostate cancer prior to documented clinical metastases. Most urologists and radiation oncologists are very familiar with the initial very common clinical scenario, commonly called "biochemical recurrence." In fact, up to 70,000 men each year will have a PSA-only recurrence after failed definitive therapy. The ideal salvage therapy for these men is not clear and includes salvage local therapies and systemic approaches, of which the mainstay is hormonal therapy. Treatment needs to be individualized based upon the patient's risk of progression and the likelihood of success and the risks involved with the therapy. It is unknown how many men per year progress with rising PSA while on hormonal therapy without documented metastases. This rising PSA disease state is sometimes called, "PSA-only hormone-refractory prostate cancer." As in the setting of initial biochemical recurrence, evidence-based treatment options are limited, and taking a risk-stratified approach is justified. In this article, we will explore these prostate cancer disease states with an emphasis on practical, clinically applicable approaches.
High-dose combination chemotherapy followed by autologous peripheral-blood stem cell transplant produced durable remissions in metastatic testicular cancer patients who relapsed or failed to respond to traditional therapy
The treatment of metastatic renal cell carcinoma (RCC) has changed dramatically over the past few years. An improved understanding of the biology of RCC has resulted in the development of novel targeted therapeutic agents that have altered the natural history of this disease. In particular, the hypoxia-inducible factor (HIF)/vascular endothelial growth factor (VEGF) pathway and the mammalian target of rapamycin (mTOR) signal transduction pathway have been exploited. Sunitinib malate (Sutent), sorafenib tosylate (Nexavar), bevacizumab (Avastin)/interferon alfa, and temsirolimus (Torisel) have improved clinical outcomes in randomized trials by inhibiting these tumorigenic pathways. Combinations and sequences of these agents are being evaluated. Other novel multitargeted tyrosine kinase inhibitors (pazopanib and axitinib) and mTOR inhibitors (everolimus) are in clinical development. Recently reported and ongoing clinical trials will help further define the role of these agents as therapy for metastatic RCC.
Docetaxel (Taxotere)-based chemotherapy (with prednisone) maintained long-term efficacy as a treatment for advanced (metastatic) hormone-resistant prostate cancer patients, according to the 3-year updated results of the landmark TAX 327 study.
A new paradigm of prostate cancer treatment is emerging that includes active surveillance with delayed treatment even for younger men with low-risk disease
An updated analysis from the pivotal phase III trial of sunitinib (Sutent) in 750 previously untreated patients with metastatic renal cell cancer (RCC) has reaffirmed the superior efficacy of sunitinib, compared with interferon-alfa (IFN-a) and shown that the agent prolongs progression-free survival (PFS) across all patient groups
Prostatic acid phosphatase (PAP) emerged as the world's first clinically useful tumor marker in the 1940s and 1950s. With the introduction of the prostate-specific antigen (PSA) test in the 1980s, which performed significantly better than PAP in terms of screening and monitoring response to treatment, PAP fell into disfavor. An increasing number of recent studies have identified PAP as a significant prognostic factor for patients with intermediate- and high-risk prostate cancer. PAP appears to be particularly valuable in predicting distant failure in higher-risk patients for whom high levels of local control are achieved with aggressive initial local treatment. As prostate cancer care becomes increasingly focused on identifying the minority of patients who would benefit from aggressive systemic therapy, a reevaluation of the potential contribution of the prostatic acid phosphatase test seems timely.
Endocare, Inc, a medical device company focused on the development of minimally invasive technologies for tissue and tumor ablation, announced that a randomized clinical trial of 244 men with localized prostate cancer demonstrated that cryoablation, a minimally invasive method of freezing cancerous tumors to destroy them, is at least as effective as external-beam radiation when used to treat localized prostate cancer
Wyeth Pharmaceuticals recently announced that the US Food and Drug Administration (FDA) has approved temsirolimus (Torisel) for patients with advanced renal cell carcinoma (RCC).
patient is a 67-year-old male with mild obstructive symptoms and an American Urology Association symptom score of 8.[1] He was noted to have a prostate-specific antigen (PSA) level of 3.2 ng/mL. Because this represented a significant increase in his PSA velocity (rate of change over time), he proceeded to have a biopsy, which was positive for prostate cancer. He has no other complaints and visits us for an opinion on the treatment of his prostate cancer.
Focal cryoablation for prostate cancer—the so-called male lumpectomy—appears to be an effective alternative to treatments that involve the whole gland, with lower rates of adverse effects
Dutasteride, a 5-alpha-reductase (SRD5A) inhibitor currently used to treat benign prostatic hyperplasia (BPH), produces genetic changes in normal prostate tissue that may be protective against the development of prostate cancer
Men with low- and intermediate-risk early-stage prostate cancer who received external-beam radiation therapy (RT) did not live as long as those who were treated with brachy-therapy or radical prostatectomy, researchers said at ASCO's 2007 Prostate Cancer Symposium
FDA officials have granted regular approval to Sutent (sunitinib malate, Pfizer) for the treatment of advanced renal cell carcinoma (RCC) patients who failed prior cytokine-based therapy, upgrading it from the accelerated approval granted in January 2006.
There has been a resurgence of interest in developing noncytotoxic immune therapies for patients with either hormone-naive biochemically relapsed post-primary therapy or castrate metastatic prostate cancer. The rationale for developing an immunotherapeutic approach has been based on the overexpression and underglycosylation of a wide variety of altered "self" molecules including prostate-specific antigen (PSA), acid phosphatase (ACP), prostate stem cell antigen (PSCA), and prostate-specific membrane antigen (PSMA), which can serve as targets for immune recognition and attack. In addition, such a strategy could theoretically make use of the patient's immune system to fight the tumor particularly if their disease is of reasonably low volume. A variety of immunotherapeutic approaches have been explored through phase I, II, and now phase III trials demonstrating that immunologic tolerance could be broken, as evidenced by the development of high-titer antibodies and T-cell responses specific for the tumor. What appears to be revolutionizing the immunotherapy field is the combination of vaccines with cytokines or immune modulators, which not only potentiate immune reactivity in vivo but foster dramatic antitumor responses. This review explores the challenges now faced in establishing a role for immune therapies for prostate cancer treatment.
There has been a resurgence of interest in developing noncytotoxic immune therapies for patients with either hormone-naive biochemically relapsed post-primary therapy or castrate metastatic prostate cancer. The rationale for developing an immunotherapeutic approach has been based on the overexpression and underglycosylation of a wide variety of altered "self" molecules including prostate-specific antigen (PSA), acid phosphatase (ACP), prostate stem cell antigen (PSCA), and prostate-specific membrane antigen (PSMA), which can serve as targets for immune recognition and attack. In addition, such a strategy could theoretically make use of the patient's immune system to fight the tumor particularly if their disease is of reasonably low volume. A variety of immunotherapeutic approaches have been explored through phase I, II, and now phase III trials demonstrating that immunologic tolerance could be broken, as evidenced by the development of high-titer antibodies and T-cell responses specific for the tumor. What appears to be revolutionizing the immunotherapy field is the combination of vaccines with cytokines or immune modulators, which not only potentiate immune reactivity in vivo but foster dramatic antitumor responses. This review explores the challenges now faced in establishing a role for immune therapies for prostate cancer treatment.
There has been a resurgence of interest in developing noncytotoxic immune therapies for patients with either hormone-naive biochemically relapsed post-primary therapy or castrate metastatic prostate cancer. The rationale for developing an immunotherapeutic approach has been based on the overexpression and underglycosylation of a wide variety of altered "self" molecules including prostate-specific antigen (PSA), acid phosphatase (ACP), prostate stem cell antigen (PSCA), and prostate-specific membrane antigen (PSMA), which can serve as targets for immune recognition and attack. In addition, such a strategy could theoretically make use of the patient's immune system to fight the tumor particularly if their disease is of reasonably low volume. A variety of immunotherapeutic approaches have been explored through phase I, II, and now phase III trials demonstrating that immunologic tolerance could be broken, as evidenced by the development of high-titer antibodies and T-cell responses specific for the tumor. What appears to be revolutionizing the immunotherapy field is the combination of vaccines with cytokines or immune modulators, which not only potentiate immune reactivity in vivo but foster dramatic antitumor responses. This review explores the challenges now faced in establishing a role for immune therapies for prostate cancer treatment.
Hormone-refractory prostate cancer (HRCaP) is both heterogeneous and lethal. Multiple treatment options exist, including secondary hormonal manipulations, chemotherapy, experimental options, and best supportive care. Choosing the appropriate therapy for an individual patient depends on several important clinical factors such as the presence or absence of symptomatic metastatic disease, age and comorbidities, and prostate-specific antigen velocity. While only docetaxel (Taxotere)-based chemotherapy has been proven to improve survival in this setting, a wide range of therapies may be effective for any individual. Palliative maneuvers, such as external-beam radiation, bisphosphonate therapy, radiopharmaceuticals, and pain management are critical for appropriate patient management. Several promising novel therapies are in late-stage testing and will hopefully provide more treatment options for these patients.
Hormone-refractory prostate cancer (HRCaP) is both heterogeneous and lethal. Multiple treatment options exist, including secondary hormonal manipulations, chemotherapy, experimental options, and best supportive care. Choosing the appropriate therapy for an individual patient depends on several important clinical factors such as the presence or absence of symptomatic metastatic disease, age and comorbidities, and prostate-specific antigen velocity. While only docetaxel (Taxotere)-based chemotherapy has been proven to improve survival in this setting, a wide range of therapies may be effective for any individual. Palliative maneuvers, such as external-beam radiation, bisphosphonate therapy, radiopharmaceuticals, and pain management are critical for appropriate patient management. Several promising novel therapies are in late-stage testing and will hopefully provide more treatment options for these patients.
Hormone-refractory prostate cancer (HRCaP) is both heterogeneous and lethal. Multiple treatment options exist, including secondary hormonal manipulations, chemotherapy, experimental options, and best supportive care. Choosing the appropriate therapy for an individual patient depends on several important clinical factors such as the presence or absence of symptomatic metastatic disease, age and comorbidities, and prostate-specific antigen velocity. While only docetaxel (Taxotere)-based chemotherapy has been proven to improve survival in this setting, a wide range of therapies may be effective for any individual. Palliative maneuvers, such as external-beam radiation, bisphosphonate therapy, radiopharmaceuticals, and pain management are critical for appropriate patient management. Several promising novel therapies are in late-stage testing and will hopefully provide more treatment options for these patients.
