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)

We evaluated the effectiveness of combination chemotherapy using estramustine and velban for metastatic prostate cancer. Patients with progressive metasatatic prostate cancer and rising prostate-specific antigen (PSA) values were evaluated between 1992 and 1994. All treatment was given on an outpatient basis. Vinblastine, 4 mg/m2 i.v., was given weekly for 6 weeks with a 2-week rest period. Estramustine, 10 mg/kg orally, was given in three divided doses for 6 weeks with a 2-week rest period between cycles. Of 15 patients, six (40%) had a response, in which a 25% decrease in PSA was associated with subjective improvement. There were no complete responses. Five partial responders had less pain. Median duration of response or time to progression was 9 months. Survival was 11.7 months for responders, 13.2 months for nonresponders. The combination of estramustine and velban is an effective therapy in progressive metastatic prostate cancer as measured by a decrease in PSA and improvement of symptoms.
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PMID:Symptomatic improvement associated with combined estramustine and vinblastine chemotherapy for metastatic prostate cancer. 893 76

The management of metastatic prostate cancer that has relapsed after initial hormonal manipulation remains a major problem, with the majority of patients dying within 12 months. Their clinical course is frequently characterized by progressive debilitation, pain, and other tumor-related symptoms. A phase II, non-randomized multicenter clinical trial was carried out in Australia in 1985-1986 to assess the efficacy and toxicity of mitoxantrone. Substantial anticancer activity was shown against hormone-refractory prostate cancer, indicated by reduction in tumor-related symptoms, improvement in quality of life indices, and a median survival of 10 months in patients with a heavy tumor burden. Although it is not possible to equate this nonrandomized series more fully with current experience since routine prostate-specific antigen measurement was not performed, the median survival of 10 months was equivalent to or better than the survival times reported from most other institutional reports of the time. Even more importantly, however, major improvements were noted in such subjective indices as reduction in pain, weight gain, and performance status. Toxicity was also acceptable, with the major side effect being asymptomatic myelosuppression.
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PMID:Management of hormone-resistant prostate cancer: an Australian trial. 899 80

The identification of active chemotherapeutic agents for use in the treatment of advanced hormone-refractory prostate cancer remains a priority of clinical research. An estimated 317,100 new cases will be diagnosed in 1996. This increased diagnosis of disease can be directly attributed to the widespread use of screening serum prostate-specific antigen. However, this has not been associated with a reduction in mortality; more than 41,000 men in the United States are expected to die of the disease this year. The natural history of hormone-resistant disease has remained unaltered, with patients having a median survival of only approximately 12 months. Use of surrogate endpoints, such as a reduction in prostate-specific antigen or improvement in pain, may be appropriate for the evaluation of novel agents or combinations. A number of promising new approaches have been recently tested and brought to trial, including combined antimicrotubular therapy, camptothecins, and matrix metalloproteinase inhibitors. It is only through the development of these and other novel compounds that we can hope to affect the natural course of prostate cancer.
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PMID:New therapeutic agents for hormone-refractory prostate cancer. 899 86

Long misclassified as an alkylating agent, estramustine phosphate is a stable conjugate of estradiol and nornitrogen mustard with antimitotic properties. Binding of the drug to microtubule-associated proteins, tubulin, and proteins of the nuclear matrix are presently considered to be the most likely mechanisms underlying the cytotoxicity of estramustine in androgen-independent prostatic carcinoma. Identification of these mechanisms of action has led to clinical reevaluation of estramustine phosphate (EMP) in several rationally designed drug combinations. Combination of EMP with either vinblastine, paclitaxel or etoposide has produced antitumor responses in 30% to 60% of patients with metastatic hormone-refractory prostate carcinoma as determined by reduction in bidimensionally measurable soft tissue disease, pain, and serum prostate-specific antigen. Whereas the antitumor activity of the combinations has been greater than additive for the single agents, the toxicities of treatment have not been greater than predicted for the individual drugs. The promising results of EMP-based chemotherapy encourage additional laboratory and clinical investigations to develop more effective therapy for hormone-refractory disease and for selected patients with earlier stages of prostate cancer.
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PMID:Estramustine-based chemotherapy. 905 Jan 35

The use of standard assessment criteria to evaluate therapeutic responses in patients with advanced prostate cancer is confounded by the high percentage of patients with bone-only metastatic disease. In an effort to develop a reliable means of assessing the activity of various therapeutic interventions, the role of prostate-specific antigen (PSA) as a response parameter is being actively evaluated. The precise role of PSA in this setting remains undefined as there is limited and sometimes conflicting findings in the literature. Additionally, there is emerging data to suggest that various therapeutic agents may influence PSA expression in a manner unrelated to the impact on tumor growth. Given the high percentage of patients with bone metastases, investigators have been actively evaluating a series of new markers of bone turnover; however, the lack of acceptable specificity limits the clinical usefulness of this approach. The role of palliative endpoints such as pain and quality of life measures have been shown to be both feasible and clinically relevant in the assessment of response in patients with symptoms of advanced disease. The emergence of an enlarging subset of asymptomatic patients with PSA-only evidence of metastatic disease presents a new and pressing challenge to clinicians to develop reliable new methods of assessing disease response to therapeutic interventions.
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PMID:Metastatic prostate cancer: assessment of response to systemic therapy. 905 Jan 37

Second-line palliative treatment of patients who have failed hormone therapy for advanced prostate cancer remains an important challenge in this disease. Very few agents have been shown to have a positive impact on survival, and toxicity is often therapy limiting in this elderly group of patients. Improvements in pain and performance status with maintenance of a reasonable functional status are worthwhile goals of any therapy at this stage. The earlier diagnosis of progressive disease from a rising prostate-specific antigen (PSA), and the use of validated quality of life questionnaires, can lead to useful improvements in the quality of the lives of these patients whose quantity we cannot at present lengthen.
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PMID:Second-line treatment of metastatic prostatic carcinoma. 914 91

Twenty-four assessable patients with hormone-resistant prostate cancer (HRPC) were to receive daily doses of oral estramustine phosphate (EMP), 10 mg kg(-1), and intravenous epirubicin (EPR) infusions, 100 mg m(-2), every third week up to a cumulative dose of 500 mg m(-2). Biochemical response [> or = 50% reduction in pretreatment serum prostate-specific antigen (PSA) after three cycles of > or = 3 weeks' duration] was demonstrated in 13 of 24 patients included (54%). No objective response (WHO criteria) was observed, although seven of nine evaluable patients achieved a > or = 50% serum PSA reduction. Subjective improvement (pain score, performance status) occurred in 7 of 24 patients, whereas nine patients progressed subjectively. There was no correlation between subjective and biochemical response. Biochemical progression (> or = 50% increase of nadir PSA) occurred after a median of 12 weeks. All but two patients were alive after a median follow-up time of 8.7 months for surviving patients (range 3.3-13.2). Eight patients experienced grade 3/4 leucopenia, with no indication of cumulative myelosuppression. Cardiovascular toxicity was experienced by four patients. Two patients developed angioedema twice, in one patient requiring hospitalization at the intensive ward. Based on this limited series, the combination of EPR and EMP in patients with HRPC is tolerable and appears to be effective in terms of significant PSA reduction. The results warrant further investigations of the two drugs and, in particular, of the clinical significance of > or = 50% PSA decrease in patients with HRPC.
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PMID:Epirubicin combined with estramustine phosphate in hormone-resistant prostate cancer: a phase II study. 921 39

Prostate cancer metastatic to the penis is rare. We describe a patient who had a painful nodule in the corpora cavernosa during adjuvant radiotherapy after radical prostatectomy for prostate cancer. Biopsy of the nodule revealed a poorly differentiated adenocarcinoma. Immunohistochemical staining for prostate-specific antigen confirmed a prostatic origin for the neoplasm. The lesion to the penis was treated with radiation therapy in conjunction with androgen deprivation therapy. The penile pain completely resolved, and the patient remains alive, 30 months after initiation of therapy.
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PMID:Prostate cancer metastatic only to the penis. 930 14

In a pilot trial, we treated thirty-three hormone resistant metastatic prostate cancer patients with a combination of androgen blockade plus weekly cytotoxic therapy and determined both response and toxicity in 32 of them. Their median Karnofsky performance status at the time of entry was 65. We administered Epidoxorubicin (EpiDx) intravenously, at a dose of 35 mg/m2, every week for 4 months. Initially, all patients had only hormonal therapy and chemotherapy was added once they progressed. In terms of W.H.O. criteria, 9 patients (28%) had a partial response, the disease was stable in 14 (44%), and progressive in 9 (28%); even in this last group, 6 patients with bone metastases experienced lasting relief from pain. No patients had to interrupt treatment due to leukopenia or cardiotoxicity. Other toxicities, including nausea and vomiting, mucositis and alopecia, were mild. Pretreatment prostate-specific antigen (PSA) levels decreased significantly (p < 0.05) in 26 patients (81%) after treatment. In our view, weekly EpiDx administration serves as an active regimen in hormone-refractory prostate cancer.
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PMID:Weekly epidoxorubicin therapy in hormone-refractory metastatic prostate cancer. 942 86

The class I IgG receptor (Fc gamma RI or CD64 receptor), which is present on key cytotoxic effector cells, has been shown to initiate the destruction of tumor cells in vitro and has been hypothesized to play a role in the destruction of antibody-coated cells such as platelets in idiopathic thrombocytopenia purpura (ITP). This overview summarizes the clinical experience with CD64-directed immunotherapy in cancer patients with the bispecific antibodies MDX-447 [humanized Fab anti-CD64 x humanized Fab anti-(epidermal growth factor receptor, EGFR)] and MDX-H210 (humanized Fab anti-DC64 x Fab anti-HER2/neu), and with the anti-CD64 monoclonal antibody (mAB) MDX-33 (H22) in the modulation of monocyte CD64 in vivo. In an ongoing phase I/II open-label trial with progressive dose escalation (1-15 mg/m2), patients with treatment refractory EGFR-positive cancers (renal cell carcinoma (RCC), head and neck, bladder, ovarian, prostate cancer and skin cancer) are treated weekly with intravenous MDX-447, with and without granulocyte-colony-stimulating factor (G-CSF). MDX-447 has been found to be immunologically active at all doses, binding to circulating monocytes and neutrophils (when given with G-CSF), causing monocytopenia and stimulating increases in circulating plasma cytokines. MDX-447 is well tolerated, the primary toxicities being fever, chills, blood pressure lability, and pain/ myalgias. Of 36 patients evaluable for response, 9 have experienced stable disease of 3-6 month's duration. The optimal dose and the maximal tolerated dose (MTD) have yet to be defined; dose escalation continues to define better the dose, toxicity, and the potential therapeutic role of this bispecific antibody. Three MDX-H210 phase II trials are currently in progress, all using the intravenous dose of 15 mg/m2 given with granulocyte/macrophage (GM-CSF). These consist of one trial each in the treatment of RCC patients, patients with prostate cancer, and colorectal cancer patients, all of whom have failed standard therapy. At the time of writing, 11 patients have been treated in these phase II trials. Four patients have demonstrated antitumor effects. Patients demonstrating responses include 2 with RCC and 2 with prostate cancer. One RCC patient has had a 54% reduction in size of a hepatic metastatic lesion and the other has had a 49% decrease in the size of a lung metastasis with simultaneous clearing of other non-measurable lung lesions. Regarding the two patients with prostate cancer, one has had a 90% reduction in serum prostate-specific antigen (PSA; 118-11 ng/ml), which has persisted for several months; the other patient with prostate has had a 70% reduction of serum PSA (872 ng/ml to 208 ng/ml) within the first month of treatment. Both patients have also demonstrated symptomatic improvement. In a completed phase I and in ongoing phase I/II clinical trials, patients with treatment-refractory HER2/neu positive cancers (breast, ovarian, colorectal, prostate) have been treated with MDX-H210, which has been given alone and in conjunction with G-CSF, GM-CSF, and interferon gamma (IFN gamma). These trials have been open-label, progressive dose-escalation (0.35-135 mg/m2) studies in which single, and more often, multiple weekly doses have been administered. MDX-H210 has been well tolerated, with untoward effects being primarily mild-to-moderate flu-like symptoms. The MTD has not yet been defined. MDX-H210 is immunologically active, binding to circulating monocytes, causing monocytopenia, as well as stimulating increases in plasma cytokine levels. Furthermore, some patients have evidence of active antitumor immunity following treatment with MDX-210. Antitumor effects have been seen in response to MDX-H210 administration; these include 1 partial, 2 minor, and 1 mixed tumor response; 15 protocol-defined stable disease responses have occurred. (ABSTRACT TRUNCATED)
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PMID:Clinical experience with CD64-directed immunotherapy. An overview. 943 76


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