Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies of docetaxel have demonstrated improved survival over mitoxantrone and prednisone in patients with hormone-refractory prostate cancer (HRPC), supporting the study of novel docetaxel-containing regimens as primary therapy or following initial docetaxel-based therapy. To evaluate the combination of docetaxel and vinorelbine in the treatment of patients with HRPC, 40 patients with proven adenocarcinoma of the prostate with progressive metastatic disease despite androgen ablation were enrolled onto this phase II trial. Patients were treated with docetaxel 60 mg/m2 on day 1 and vinorelbine 15 mg/m2 on days 1 and 8 of a 21-day cycle. All patients received dexamethasone 8 mg twice daily for 4 days starting 1 day prior to the docetaxel infusion. After the first three patients were enrolled, filgrastim was added on days 2-6 and 9-13. Of the 40 patients enrolled, 19 had no prior chemotherapy and 21 had received at least one prior chemotherapy regimen. Of the 19 patients without prior chemotherapy and the 21 with prior chemotherapy, 7 (37%) and 6 (29%) , respectively, demonstrated a decrease in prostate specific antigen by > 50% maintained for at least 4 weeks. Out of eight patients with measurable disease, one achieved a partial response and four demonstrated stable disease. There was one patient with deep vein thrombosis, and febrile neutropenia was noted in only three patients after the protocol was modified to include filgrastim support. The combination of docetaxel and vinorelbine with filgrastim was well tolerated and active against HRPC in patients with or without prior chemotherapy.
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PMID:A phase II trial of docetaxel and vinorelbine in patients with hormone-refractory prostate cancer. 1583 57

Androgen-deprivation therapy, usually with combined androgen blockade, is standard initial treatment for advanced prostate cancer. With failure of initial treatment, as indicated by rising prostate-specific antigen (PSA) levels, second-line hormonal therapy is usually instituted. Over the past several years, it has become increasingly clear that systemic chemotherapy has an important role in hormone-refractory disease. Phase II trials have demonstrated high PSA and measurable disease response rates with taxane single-agent and combination treatments. One recent phase III trial showed that docetaxel (Taxotere)/ estramustine (Emcyt) significantly improved overall survival, progression-free survival, and PSA response rate compared with mitoxantrone (Novantrone) plus prednisone. Another phase III trial demonstrated that docetaxel given every 3 weeks plus prednisone significantly improved overall survival, PSA response rate, pain relief response rate, and quality of life compared with mitoxantrone and prednisone. On the basis of these findings, every-3-week docetaxel plus prednisone is now considered standard first-line therapy for metastatic hormone-refractory disease. There is considerable optimism that treatment can be further improved. Studies of taxane combinations with bevacizumab (Avastin), thalidomide (Thalomid), bortezomib (Velcade), antisense Bcl-2 oligonucleotide, mTOR inhibitors, epidermal growth factor receptor inhibitors, and KDR inhibitors are under way. Randomized phase III trials in progress or planned are examining docetaxel in combination with imatinib mesylate (Gleevec) or calcitriol and docetaxel/prednisone in combination with bevacizumab and an antisense clusterin compound. Other promising systemic agents include epothilones and atrasentan, and promising vaccines include Provenge, GVAX, and Prostvac.
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PMID:Recent progress in management of advanced prostate cancer. 1594 43

As increasing numbers of men are living longer with prostate cancer, larger proportions will eventually present to our collective practices with increasing prostate-specific antigen (PSA) levels. Such PSA relapses, conservatively estimated to affect approximately 50,000 men each year, have become the most common form of advanced prostate cancer. Salvage radiation therapy and salvage prostatectomy have important roles in our therapeutic armamentarium and should be valid options for young, healthy men. Counseling patients regarding expectations for cancer control and treatment morbidity has become better because of reports from larger series of patients who have had salvage radiation therapy and surgery. Some patients may not be appropriate candidates for salvage local therapies. A growing body of evidence suggests early hormonal therapy improves progression-free survival (PFS) and could alter cancer-specific survival. This benefit seems to be greatest when hormonal therapy is initiated while PSA levels are low, before clinically measurable disease becomes apparent. However, there is a cost to be paid in side effects and health care dollars when androgen deprivation is administered over prolonged periods. The nonsteroidal antiandrogen agent bicalutamide could offer PFS equivalent to that seen with castration without the complications of androgen deprivation. Observational data seem to indicate that individuals at high risk could also receive benefit from therapy administered before PSA detection. The potential opportunities for novel therapeutic agents with low associated morbidity are great.
Clin Prostate Cancer 2005 Jun
PMID:Treating the biochemical recurrence of prostate cancer after definitive primary therapy. 1599 60

ASCENT, the Androgen-Independent Prostate Cancer (AIPC) Study of Calcitriol Enhancing Taxotere, is a double-blind, placebo-controlled randomized clinical trial designed to determine if DN-101, a high-dose oral formulation of calcitriol designed for cancer therapy, significantly increases the proportion of patients who have > 50% reduction in serum prostate-specific antigen (PSA) levels in response to docetaxel. The secondary goals of ASCENT are to evaluate the effect of DN-101 combined with docetaxel on PSA progression-free survival, tumour response rate in measurable disease, tumour progression-free survival, skeletal morbidity-free survival, clinical progression-free survival, and overall survival, and to examine the safety and tolerability of DN-101 combined with docetaxel. ASCENT builds on phase I work showing that weekly dosing allows substantial dose-escalation of calcitriol, the natural ligand for the vitamin D receptor, and on phase II work that suggested that adding weekly high-dose 'pulse' calcitriol may enhance the activity of weekly docetaxel in patients with AIPC. The preclinical rationale for calcitriol and its combination with docetaxel for prostate cancer therapy is reviewed, as are the key clinical trials that led to the development of ASCENT. The ASCENT design and its strengths and limitations are presented.
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PMID:ASCENT: the androgen-independent prostate cancer study of calcitriol enhancing taxotere. 1610 1

Prostate cancer, the most common male cancer, affects one in eight American men. Risk factors for the disease include increased age, race, and family history of prostate cancer. To date, surgery, radiation, and hormonal therapy have been the mainstays of treatment. In the past, chemotherapy served only a palliative role for men with prostate cancer and failed to produce a survival advantage or any significant measurable disease response. However, for the first time, docetaxel-based regimens have demonstrated improved survival in men with hormone-refractory prostate cancer in two different, large, phase III studies. Additionally, a number of novel agents are being developed with the hope that treatment for men with hormone-refractory prostate cancer will be improved. Oncology nurses provide critical symptom management strategies as well as education to men with prostate cancer and their partners. Therefore, maintaining current state of the knowledge about best practices and treatment for prostate cancer is crucial. This, in turn, directs efforts to educate patients and family members about treatments and management of side effects.
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PMID:Hormone-refractory prostate cancer: a shifting paradigm in treatment. 1670 6

Prostate cancer represents an ideal target for radioimmunotherapy based on the pattern of spread, including bone marrow and lymph nodes, sites that typically receive high levels of circulating antibody, and the small volume of disease, ideally suited for antibody delivery and antigen access. This review explores possible antibody targets in prostate cancer and focuses on the potential role for radioimmunotherapy by highlighting several clinical trials involving radiolabeled anti-prostate-specific membrane antigen monoclonal antibody J591. Prostate-specific membrane antigen, a highly prostate-restricted transmembrane glycoprotein with increased expression in high-grade, metastatic, and hormone-refractory disease, represents an ideal target for monoclonal antibody therapy in prostate cancer. Radiolabeled anti-prostate-specific membrane antigen monoclonal antibody J591 trials using the radiometals yttrium-90 and lutetium-177 have demonstrated manageable myelotoxicity, no significant nonhematologic toxicity, excellent targeting of soft-tissue and bone metastases, and preliminary efficacy including prostate-specific antigen and measurable disease responses. Additional studies are under way to better define the activity of radiolabeled antibody therapy as well as the role for fractionated therapy and combination approaches with taxane-based chemotherapy.
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PMID:Clinical utility of radiolabeled monoclonal antibodies in prostate cancer. 1672 7

Chemotherapy has historically proven toxic and ineffective for the treatment of metastatic hormone-refractory prostate cancer (HRPC), a disease with substantial morbidity and mortality. Progress has been made in symptom relief, and the combination of mitoxantrone and prednisone is considered the palliative standard of care. The effects of a variety of chemotherapeutic agents, both alone and in combination, on prostate-specific antigen decline rates, measurable disease response, and survival have been examined in numerous phase I and II trials. Results suggest that combining vinblastine or paclitaxel with estramustine confers a survival advantage over either agent alone. In addition, docetaxel-based therapy has been found to be effective and well tolerated, and phase III trials will soon determine whether docetaxel-based therapy should replace mitoxantrone-based therapy as the standard of care for HRPC.
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PMID:Docetaxel for the treatment of hormone-refractory prostate cancer. 1698 45

Chemotherapy has historically proven toxic and ineffective for the treatment of metastatic hormone-refractory prostate cancer (HRPC), a disease with substantial morbidity and mortality. Progress has been made in symptom relief, and the combination of mitoxantrone and prednisone is considered the palliative standard of care. The effects of a variety of chemotherapeutic agents, both alone and in combination, on prostate-specific antigen decline rates, measurable disease response, and survival have been examined in numerous phase I and II trials. Results suggest that combining vinblastine or paclitaxel with estramustine confers a survival advantage over either agent alone. In addition, docetaxel-based therapy has been found to be effective and well tolerated, and phase III trials will soon determine whether docetaxel-based therapy should replace mitoxantrone-based therapy as the standard of care for HRPC.
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PMID:Docetaxel for the treatment of hormone-refractory prostate cancer. 1698 41

Based on the pre-clinical spectrum of activity in taxane-resistant cell lines, we evaluated KOS-862 (epothilone D; 12,13-desoxyepothilone B) as second-line chemotherapy in androgen-independent prostate cancer.Thirty-eight men with metastatic androgen-independent prostate cancer and evidence of progression following docetaxel-based chemotherapy were treated with KOS-862, 100 mg/m(2) (maximum of 240 mg) i.v. weekly for 3 weeks, repeated every 4 weeks. The primary objective for this study was to determine the antitumor activity, measured by PSA decline by more then 50% confirmed 4 weeks later. Two patients (5.3%, 90% CI 1-16%) met criteria for confirmed PSA decline. While both of these patients had previously been treated with docetaxel, neither had confirmed docetaxel-refractory disease. None of the 24 patients with measurable disease had a confirmed partial response. Seventy-three percent of patients had an adverse event leading to dose delay, reduction, or treatment discontinuation. Neurological toxicity and fatigue predominated. Seventeen patients (44.7%) had treatment related grade 3 neurological adverse events including peripheral sensory neuropathy (n = 4, 10.5%), ataxia (n = 3, 7.9%), peripheral motor neuropathy (n = 1, 2.6%), involuntary muscle contractions (n = 1, 2.6%) and neuropathic pain (n = 1, 2.6%). One subject (2.6%) had a grade 4 treatment peripheral motor neuropathy. Further study of this dose and schedule of KOS-862 in this patient population cannot be recommended due to both lack of activity and excessive toxicity.
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PMID:Phase II study of KOS-862 in patients with metastatic androgen independent prostate cancer previously treated with docetaxel. 1761 7

The results of the TAX 327 and SWOG 99-16 trials for the first time showed an improvement in overall survival (OS) with docetaxel-based chemotherapy in patients with metastatic hormone-refractory prostate cancer. As such, 3-weekly (q3w) docetaxel plus low-dose prednisone is widely considered to be the treatment of choice for these patients. An updated survival analysis from TAX 327 confirms that benefits observed with docetaxel are sustained at 3 years. Furthermore, q3w docetaxel plus prednisone was effective in all patient subgroups investigated, regardless of age, presence or absence of pain, and performance status. Multivariate analysis has shown that prostate-specific antigen (PSA) concentrations and kinetics (pre-treatment PSA doubling time; PSADT) are independent prognostic factors for survival in the TAX 327 cohort, along with pain, number of metastatic sites and measurable disease. Patients with baseline PSA concentrations of <114 ng/mL and PSADT > or =55 days have a median overall survival of 25 months while those with PSA concentrations of > or =114 ng/mL and a PSADT of <55 days have a median overall survival of only 14 months. A PSA decline of > or 1=30% within 3 months' therapy with docetaxel is also a surrogate of OS. Measurements such as these, and the use of predictive nomograms, can assist the physician in identifying patients at high risk of disease progression who may benefit from earlier treatment with chemotherapy.
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PMID:Chemotherapy in hormone-refractory prostate cancer. 1830 87


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