Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent years have seen a downward shift in the most common disease stage at diagnosis and in the age of patients diagnosed with prostate cancer. Although younger men with clinically localized disease are generally offered radiotherapy or radical prostatectomy, such treatment does not always produce a cure. Adjuvant hormonal therapy (medical or surgical castration) has been shown to extend progression-free survival in both the radiotherapy and surgical settings, and overall survival benefits have also been demonstrated in some studies. However, castration is associated with sexual dysfunction that may be unacceptable, particularly among younger patients. The ongoing bicalutamide (Casodex; AstraZeneca Pharmaceuticals, Wilmington, DE) Early Prostate Cancer program is evaluating the efficacy and tolerability of bicalutamide 150 mg as immediate therapy, either alone or as an adjuvant to therapy of curative intent, in patients with localized or locally advanced prostate cancer. This is the largest clinical trial program in prostate cancer treatment to date, comprising 3 randomized, double-blind, placebo-controlled studies with a total of 8113 patients. At median follow-up period of 3 years and after 922 progression events, the bicalutamide group had a significant reduction of 42% in the risk of objective progression compared with patients who received placebo plus standard care. The risk of prostate-specific antigen progression was also significantly reduced by 59%. As expected, gynecomastia and breast pain were the most frequently reported side effects of bicalutamide therapy. A longer follow-up period will determine whether the reduced risk of progression will translate into cause-specific and overall survival benefit for these patients.
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PMID:Emerging role of adjuvant hormonal therapy. 1223 Oct 39

In this phase I/II clinical trial the antitumor activity of high-dose tamoxifen when administered in combination with vinblastine was assessed and the toxicity profile of this combination characterized. All 25 patients enrolled in this study were required to have androgen-independent prostate cancer and to maintain androgen ablation during treatment. Vinblastine was given by continuous infusion over 5 days. Doses were increased from 0.9 mg/m2/day to 1.5 mg/m2/day in successive cohorts of at least 3 patients, with no further escalation even in the absence of dose-limiting toxicity. Intra-patient dose escalation was permitted. Tamoxifen was administered at a dose of 200 mg/kg on day 1, then 120 mg/kg/day on day 2. Standard response criteria were utilized to assess antitumor activity and CTC toxicity criteria were used. Quality of life (QOL) pain assessments were evaluated at each visit to the clinic. Most patients tolerated the highest dose of vinblastine at 1.5 mg/m2/day by continuous infusion over 5 days with 200 mg/kg/day of tamoxifen on day 1 and day 2. One patient had a greater than 50% decline in prostate-specific antigen that lasted for 170 days. Two patients received dose reductions because of toxicity. The most common serious toxicities included neutropenia, and fatigue. Reversible neurosensory, neuromotor, neurocortical and neurocerebellar toxicities were reported. Six of the 25 patients enrolled in the study (24%) experienced reversible neurologic toxicity of at least grade III. No statistically significant differences between precycle assessment of QOL and subsequent cycles were observed. It is concluded that vinblastine at 1.5 mg/m2/day continuous i.v. infusion combined with tamoxifen 200 mg/kg/day on day 1 and day 2 is inactive, and not without toxicity in the treatment of advanced metastatic androgen-independent prostate cancer.
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PMID:A phase I/II study of high-dose tamoxifen in combination with vinblastine in patients with androgen-independent prostate cancer. 1285 95

Increasingly transrectal ultrasound and biopsy is performed for the detection of prostate cancer. We have conducted a randomised trial to evaluate whether the addition of periprostatic local anaesthetic injection reduces the discomfort of the procedure. A total of 64 patients who attended a specialised prostate clinic and were being evaluated for an elevated prostate-specific antigen agreed to participate in the trial and were randomly allocated to two groups. The intervention group received 10 ml of 1% lignocaine in the periprostatic tissue prior to biopsy and the control group underwent a standard biopsy. All patients had a sextant biopsy under ultrasound guidance. After the procedure, they were asked to determine the severity of the pain on a scale of 0-10 and the whether the quality of the pain was mild, moderate or severe. The responses were distributed normally. The groups were compared using Student's t-test. Pain severity showed no significant difference between the two groups (P=0.14). There was a trend towards a statistical difference (P=0.07) on the qualitative pain scale. In conclusion, no significant difference in overall discomfort in men having sextant biopsies was detected between the two groups, suggesting that the administration of local anaesthetic may not be as valuable as early reports have suggested.
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PMID:A randomised trial of periprostatic local anaesthetic for transrectal biopsy. 1297 Jul 29

The endothelin (ET) axis represents a novel and exciting target in the treatment of prostate cancer. ET-1, acting primarily through the endothelin A receptor (ET(A)), is integrally involved in multiple facets of prostate cancer progression, including cell growth, inhibition of apoptosis, angiogenesis, development and progression of bone metastases, and mediation of pain responses. Clinical trials with the ET(A) antagonist, atrasentan, have demonstrated good tolerability, with the most common adverse events being headache, rhinitis, and peripheral edema. These trials have demonstrated statistically significant improvements in pain measures, prostate-specific antigen (PSA) kinetics, biologic markers of bone changes, and development of bone metastases. There have also been consistent improvements in time to progression, although not always statistically significant. Ongoing studies in a variety of patient populations will better define the role of ET receptor antagonists in the treatment of men with prostate cancer. In this article, we review the biology and pathophysiology of the ET axis in prostate cancer, critically analyze the major clinical trials reported to date, and discuss some emerging data and how it may impact the way we proceed in the future with the development of this class of drugs in prostate cancer.
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PMID:Endothelin receptor antagonists in the treatment of prostate cancer. 1457 15

Transrectal ultrasound (TRUS)-guided biopsy remains the mainstay of the diagnosis of prostate cancer. Although this diagnostic method is a safe procedure and well tolerated by most patients a significant number of patients report discomfort and pain during prostate biopsy. In order to define the best method of anesthesia, many studies, in which different methods were compared, have been performed. To determine the effectiveness of local injection anesthesia in TRUS-guided prostate biopsy, we designed and performed this prospective study in order to evaluate the utility of periprostatic nerve block for pain management. A total of 100 patients who had elevated total prostate-specific antigen (tPSA) and/or abnormal digital rectal examination (DRE) were included in this study. Half of the patients received periprostatic injection anesthesia (group I) and the remaining half received placebo (group II). Patients received 10 cm3 (5 cm3 each side) 1% lidocaine injected into the periprostatic nerve plexus under transrectal ultrasonic guidance. Pain during biopsy was assessed using a 10-point modified visual analog scale (VAS). In groups I and II, mean patient age was 66.8+2.5 and 65.6+11.5 y, mean tPSA was 7.87+/-3.6 and 11.3+/-1.7 ng/ml, mean biopsy duration was 6.5+/-2.5 and 6.6+/-2.2 min and mean pain score during TRUS-guided biopsy was 1.46+/-2.2 and 4.5+/-2.1, respectively. No statistically significant difference was observed with respect to age, tPSA and mean biopsy duration between these groups. Mean pain VAS score was statistically or significantly better (P=0.0001) in the lidocaine injection group (group I), and furthermore no patient had a VAS pain score > or =5 in this group. Only minor and transient complications occurred in both groups. This study reinforces the usage of periprostatic nerve block as a standard method of pain management during TRUS-guided prostate biopsy, because it is simple, safe, uncostly and significantly effective without requiring additional time.
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PMID:Transrectal periprostatic lidocaine injection anesthesia for transrectal prostate biopsy: a prospective study. 1466 73

A total of 28 patients were treated with mitoxantrone, vinorelbine and prednisone every 3 weeks. In all, 11 patients (46%) had a significant prostate-specific antigen decline for a median duration of 11.4 months. Eight patients (33%) achieved a partial response on pain, while seven (29%) obtained a stabilisation of the symptom. Median duration of the response was 9.5 months. A confirmed partial response was obtained in three out of seven patients who had bidimensionally measurable disease. Toxicity was manageable. Our study provides further support to the concept of combined antimicrotubule therapy for metastatic harmonoresistant prostate cancer, promoting the exploration of new regimens containing antimicrotubule agents in addition to mitoxantrone-prednisone.
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PMID:Mitoxantrone, vinorelbine and prednisone (MVD) in the treatment of metastatic hormonoresistant prostate cancer--a phase II trial. 1499 38

There is a pressing need for new agents to treat hormone-refractory prostate cancer (HRPC). Doxorubicin has shown modest activity in this setting, but its use is limited by its toxicities. Liposomal encapsulation of doxorubicin appears to promote enhanced tumor accumulation in some tumor types, and toxicity appears to be reduced. A phase II trial of liposomal doxorubicin was therefore conducted in patients with HRPC. Fourteen patients with progressive HRPC were treated. For the first dose only, patients were randomized to receive either doxorubicin 50 mg/m2 or liposomal doxorubicin 50 mg/m2 in order to evaluate exploratory pharmacokinetics. For all subsequent cycles, all patients received liposomal doxorubicin 50 mg/m2. Response to therapy was assessed with serial measurements of serum prostate-specific antigen (PSA) and sequential imaging studies. All 14 patients were evaluable for response and toxicity. Two patients (14%) had declines in serum PSA of > or = 50%. The first patient had a baseline PSA of 34.7 ng/mL and a nadir of 17.0 ng/mL. The second patient had a baseline PSA of 5580.0 ng/mL and a nadir of 200.7 ng/mL. The latter of these 2 patients had an unambiguous improvement in bone scan and a reduction in pain. Treatment was well tolerated overall. One patient was removed from treatment after the development of a grade 3 infusion reaction with the first cycle of liposomal doxorubicin. Neutropenia was the most common toxicity; in only 1 case was it grade 3, and no cases of grade 4 were seen. Doxorubicin plasma concentrations were best fit by a linear, two-compartment model. Liposomal doxorubicin plasma concentrations were best fit by a linear, one-compartment model. Treatment with liposomal doxorubicin was well tolerated overall. While monotherapy with liposomal doxorubicin has only modest activity in the treatment of HRPC, it may be of interest to study this agent as part of combination chemotherapy.
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PMID:Liposomal doxorubicin for the treatment of hormone-refractory prostate cancer. 1504 11

The objective of the trial is to evaluate the efficacy of capecitabine in patients with metastatic hormone-resistant prostate carcinoma (HRPC), in terms of prostate-specific antigen (PSA) response and clinical benefit (decrease of pain or analgesic score) and its safety profile. In all, 25 patients with HRPC were enrolled on a phase II trial of capecitabine (Xeloda) at a dose of 1250 mg m(-2) orally twice daily on days 1-14 every 21 days. The inclusion criteria were PSA serum levels >3 x upper limit of normal, a WHO performance status 0-2, age <85 years and adequate bone marrow, liver and renal function. In patients with grade 2 or higher haematological toxicity on day 1 of the treatment cycle, therapy was first delayed, and then continued at a lower dose. Trial end points were PSA response and clinical benefit defined by quality of life (QL) data and analgesic consumption. The median age of patients was 70 years (range 54-85 years). A median of three cycles of capecitabine was administered (range 1-8). PSA response was observed in three patients (12%, 95% CI 3-31%), with times to tumour progression of 18, 21 and 35 weeks, respectively. In these patients, the response durations were 12, 17 and 32 weeks, respectively. Minor PSA regression was also seen in two further patients. The median time to tumour progression of all patients was 12 weeks (95% CI 9-15 weeks). Haematological toxicity was minor, with leukopenia grade 3 observed in one patient. There were three deaths during trial treatment, respectively, due to sepsis following mucositis and leukopenia, presumed sepsis with mucositis induced by chemotherapy and concomitant radiotherapy and cerebral dysfunction progressing to coma. Hand-foot syndrome grades 2 and 3 were observed in four patients each. Clinical benefit was observed in five patients (20%, CI 7-41%). Based on toxicity data, we recommend a lower starting dose of 1000 mg x m(-2) orally twice daily. While capecitabine has some activity in HRPC, as suggested by observed PSA responses, we conclude that it is not worthwhile to investigate capecitabine monotherapy in a phase III trial. Combinations of capecitabine with other agents, such as vinorelbine or docetaxel, may prove to be more effective.
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PMID:Capecitabine in hormone-resistant metastatic prostatic carcinoma - a phase II trial. 1505 47

The development of advanced laparoscopic techniques and robot-assisted technology has resulted in several new surgical approaches for treating organ-confined prostate cancer. Outcomes with these new or minimally Invasive techniques should be assessed carefully to ensure that they are similar to or surpass patients' oncologic and functional outcomes after open radical prostatectomy. This article reviews the current published experience with minimally Invasive approaches to increase awareness about viability. Several of the larger series of patients who have undergone laparoscopic (transperitoneal and extraperitoneal) or robot-assisted laparoscopic radical prostatectomies are discussed and evaluated critically. Comparisons to published data on open radical prostatectomy are included for completeness. The different minimally invasive techniques are described and contrasted in regard to prostate-specific antigen progression-free survival, surgical margin status, blood loss, transfusion rates, postoperative pain, length of hospitalization, duration of urinary catheterization, potency, continence, and complications. The relative costs of each method are provided. The coexistence of multiple surgical approaches should and can challenge surgeons who perform open and minimally invasive procedures to strive for a new standard of care above and beyond what is accepted today to minimize patient morbidity while maximizing functional and oncologic outcomes.
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PMID:Minimally invasive radical prostatectomy. 1535 40

A prospective study was performed to investigate the combination of the aromatase inhibitor aminoglutethimide and hydrocortisone in androgen-independent prostate cancer with changes in prostate-specific antigen (PSA) level as main determinant for response. Thirty-five patients were treated with aminoglutethimide 1000 mg daily and hydrocortisone acetate 40 mg daily. PSA measurements were performed every month. If evaluable lesions were present, objective tumor assessment was done by computed tomography scan and X-ray investigations. In 12 patients (37%) the PSA value showed a confirmed response with a decline in serum level of at least 50%. Median time to progression in responding and all patients was 10.5 and 4.5 months, respectively. Median duration of response in responding patients was 9 months. Median survival for these two groups was 23 and 14.5 months, respectively. Of seven patients with measurable disease, two showed a partial response and five a stable disease. Improvement in general condition, pain and feeling of well-being was noted in two-thirds of patients. Therapy was well tolerated with mainly grade I and II adverse events in 20% of patients. We conclude that aminoglutethimide is a valuable second-line therapy for patients with androgen-independent prostate cancer.
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PMID:Effect of combination therapy with aminoglutethimide and hydrocortisone on prostate-specific antigen response in metastatic prostate cancer refractory to standard endocrine therapy. 1545 24


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