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)

This study was conducted to determine the similarity of response rates and safety produced by weekly paclitaxel with or without oral estramustine in patients with metastatic hormone-refractory prostate cancer. Between December 1998 and December 1999, 163 patients were randomized to receive 28-day cycles of paclitaxel 100 mg/m2 on days 2, 9, and 16 plus estramustine 280 mg orally 3 times a day on days 1-3, 8-10, and 15-17, or to receive paclitaxel 100 mg/m2 alone on days 1, 8, and 15. Objective response was defined as a > oe = 50% decrease in prostate-specific antigen (PSA) maintained for 4 weeks with stable or improved performance status. Response rates included 37 partial responses for paclitaxel/estramustine (47%) and 22 partial responses for paclitaxel (27%; P < 0.01). Median duration of response was 15.1 months for paclitaxel/estramustine and 15.5 months for paclitaxel; median survival was 16.1 months and 13.1 months, respectively (P = 0.049). Common toxicities for both treatments included neutropenia, gastrointestinal events, neuropathy, and asthenia. Thromboembolic events were more frequent in the paclitaxel/estramustine arm (no prophylactic anticoagulants). The rate of PSA decline for paclitaxel/estramustine was almost 2 times that of paclitaxel (47% vs. 27%), with acceptable toxicity. Multivariate analysis of prognostic factors affecting survival was not significant for treatment arm (P = 0.08). Although the incidence of thromboembolic events appeared to be increased in the paclitaxel/ estramustine arm, the addition of estramustine was responsible for a 20% increase in the rate of PSA decline. Neither treatment arm had significant impact on quality of life as measured by the Functional Assessment of Cancer Therapy-Prostate quality of life questionnaire. This study produced encouraging data; further studies of paclitaxel/ estramustine are recommended.
Clin Prostate Cancer 2004 Sep
PMID:Phase II randomized trial of weekly paclitaxel with or without estramustine phosphate in progressive, metastatic, hormone-refractory prostate cancer. 1547 94

Thalidomide has anti-angiogenic and immunomodulatory activity, exhibiting antitumour effects in patients with multiple myeloma and, more rarely, in several other solid tumours. We evaluated the single-agent antitumour activity and toxicity profile of thalidomide in patients with metastatic malignant melanoma, as well as its plasma pharmacokinetics and pharmacodynamic effects [vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF) levels]. A two-stage Gehan method was used with a stopping rule after 14 consecutive non-responding patients. Thalidomide was given orally at a daily dose of 200 mg/day, which was then escalated every 2 weeks by 200 mg/day as tolerated to a maximum of 800 mg/day. Patients were evaluated every 8 weeks for response using the World Health Organization (WHO)-27 criteria. Fourteen patients were enrolled and no objective responses were observed, with one stable disease and one mixed response. The dose-limiting toxicities were constipation, dizziness and somnolence. Other toxicities were oedema, neuropathy, dry skin, dry mouth, tremor and fatigue. The plasma pharmacokinetics of thalidomide were comparable with those of previous studies in normal volunteers and in patients with advanced prostate cancer. Serum levels of b-FGF and VEGF did not change significantly following drug administration. In conclusion, thalidomide showed poor activity, but acceptable toxicity, in patients with metastatic melanoma. Future studies should explore this agent in combination with other biological agents or cytotoxic agents, such as temozolomide.
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PMID:Phase II study of thalidomide in patients with metastatic malignant melanoma. 1557 25

Epothilones are cytotoxic macrolides with a similar mechanism of action to paclitaxel but with the potential advantage of activity in taxane-resistant settings in preclinical models. The epothilones ixabepilone, patupilone, BMS-310705, KOS-862 and ZK-EPO are in early clinical trials for cancer treatment. Phase I studies have shown that dose-limiting toxicities of epothilones are generally neurotoxicity and neutropoenia although initial studies with patupilone indicated that diarrhoea was dose limiting. Neuropathy induced by ixabepilone may be schedule dependent. Over 20 Phase II studies of epothilones in cancer treatment have been reported, and significant activity in taxane-sensitive tumour types (such as breast, lung and prostate cancers) has been noted. Response rates in taxane-refractory metastatic breast cancer are relatively modest, but ixabepilone and patupilone have shown promising efficacy in hormone-refractory metastatic prostate cancer and in taxane-refractory ovarian cancer.
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PMID:Epothilones in the treatment of cancer. 1673 19

Tumor metastasis is an important clinical problem, contributing to the majority of cancer-related deaths. The recent discovery of metastasis suppressor genes, such as N-myc downstream-regulated gene-1 (Ndrg-1), has introduced a novel approach to treating cancer and preventing metastasis. Ndrg-1 has been identified as a protein involved in the differentiation of epithelial cells. In addition, Ndrg-1 expression can be regulated by androgens and is involved in the pathology of the disease, Hereditary Motor and Sensory Neuropathy-Lom (HMSNL). However, one of the most well documented links between Ndrg-1 and pathophysiology is its association with inhibition of tumor metastasis. The expression of Ndrg-1 was found to be significantly downregulated in a variety of different neoplasms including breast, colon and prostate cancer. Furthermore, Ndrg-1 expression was shown to be negatively correlated with tumor metastasis. Studies in vitro and in vivo have demonstrated a significant reduction in the metastatic ability of cells overexpressing Ndrg-1. The ability of these cells to invade was also compromised. The Gleason grade of prostate and breast cancers was found to correlate with Ndrg-1 expression, with more advanced and poorly differentiated tumors having lower Ndrg-1 levels. Recently, Ndrg-1 expression was demonstrated to be regulated by cellular iron levels and induced by iron chelators. These latter compounds were recently identified as potential anticancer agents as they selectively prevent cancer cell proliferation and lead to apoptosis. The discovery that iron chelators also increase Ndrg-1 expression further augments their antitumor activity and provides a novel strategy for the treatment of cancer and its metastasis.
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PMID:The metastasis suppressor, Ndrg-1: a new ally in the fight against cancer. 1692 Jul 33

We describe a rare finding in a 38 year old patient with previously undiagnosed prostate cancer who presented with multiple facial swellings, mental nerve neuropathy and paraplegia. While the co-existence of paraplegia and mental nerve neuropathy is a possible feature of metastatic prostate cancer involving the spine and mandible, the concomitant occurrence of multiple facial swellings involving the anterior mandible with its related gingival and lip mucosa, frontal bone and parotid glands is a rare finding. This raised a suspicion of two histologically different malignancies co-existing in this patient. Fine needle aspiration cytology (FNAC) of the parotid lesion and incisional biopsy of the gingival lesion were reported as Lymphoblastic lymphoma and Non Hodgkin's Lymphoma respectively. A Transrectal biopsy of the prostate gland confirmed adenocarcinoma of the prostate gland. The patient however died due to a number of intercurrent illnesses and rapid deterioration consequent on his disease condition. Unfortunately, all efforts to carry out an autopsy were unsuccessful due to strong objection of the relatives on religious grounds. Problem associated with the diagnosis and management of such a rare case in a developing economy was highlighted.
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PMID:Multiple malignant lesions involving the orofacial region: a case report. 1731 48

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

Numb chin syndrome is a sensory neuropathy characterized by numbness involving the distribution of the mental nerve that could be an uncommon manifestation of metastatic malignancy. Bony metastases are common in patients with advanced prostate carcinoma and involving preferentially vertebrae, sternum, pelvic bones, ribs and femurs. We report a case in an 82-year-old man presenting a history of mental neuropathy as the isolated presenting symptom of a widespread metastatic prostate cancer Numb chin syndrome was describe in some reviews as a late component of a previously diagnosed disease but this report underline the importance of this neuropathy as the isolated presenting symptom of a widespread metastatic prostate cancer. This event is very rare and enumerates four cases in the world literature.
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PMID:Numb chin syndrome: the presenting symptom of a metastatic prostate carcinoma. 1830 31

Numb chin syndrome (NCS) is a sensory neuropathy presenting with numbness of the chin in the distribution of the mental nerve and the branches of the mandibular division of the trigeminal nerve. Though it can be caused by a benign process, NCS should be regarded as being due to malignancy until proven otherwise. Among the malignancies that cause NCS the most common are breast cancer, prostate cancer, and lymphoreticular malignancy. In squamous cell carcinoma (SCC) of the esophagus, spread to the mandible is a rare and often late event. An often overlooked clinical sign in mandibular metastases is hypoesthesia or paresthesia over the peripheral distribution of the inferior alveolar nerve/mental nerve; this sign has been referred to in the literature as NCS or numb lip syndrome or mental nerve neuropathy. Rarely, this may be the first presentation of a disseminated malignancy. Prognosis is usually poor. The discovery of this symptom should alert the clinician to the possibility of disseminated disease. In this article we report a rare case of metastatic SCC of the esophagus in a 40-year-old male patient who presented with NCS. We also review the mechanism, causes, and evaluation of NCS.
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PMID:Numb chin syndrome as a manifestation of metastatic squamous cell carcinoma of esophagus. 1929 91

Objectives of this study were to determine the maximum tolerated dose and to characterize the side effect profile and pharmacokinetics of lenalidomide in patients with advanced refractory solid tumors. Patients were treated on a modified Fibronacci dose escalation scheme with an oral daily dose of lenalidomide. A total of 45 patients with 8 different tumor types were accrued. Doses administered included 5, 10, and 20 mg continuous daily doses, every 28 days (n = 15), later modified to intermittent doses of 15, 20, 25, 30, 35, and 40 mg, with a 21 days-on and 7 days-off schedule, due to observed side effects. Lenalidomide exhibited a linear pharmacokinetics over a wide range of doses with the mean half-life of 3.9 hours. The renal function affected lenalidomide clearance, resulting in 50% reduction in patients with mild renal impairment compared with patients with normal function (CL/F = 243 mL/min). Stable disease was documented in 12 of 44 evaluable patients, of whom 9 patients had prostate cancer. Most frequent grade 1 and 2 toxicities included fatigue, nausea, pruritus/rash, neutropenia, and neuropathy. Grade 3/4 events were predominantly hematologic. Lenalidomide was well tolerated up to a 35-mg/d intermittent dosing schedule at doses higher than previously indicated for hematologic malignancies.
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PMID:Phase I study of oral lenalidomide in patients with refractory metastatic cancer. 1945 3

Prostate cancer (CaP) is one of the most common types of cancer among men and the second leading cause of cancer-related death in western countries. The risk factors for CaP are age, race/ethnicity, family history and diet. It is interesting that epidemiologic evidence suggests a history of diabetes mellitus (DM) is related to a decreased CaP risk. The cause of this association remains largely unknown. DM is a group of metabolic diseases characterized by hyperglycemia and insulin resistance. It is commonly associated with microvascular complications including diabetic retinopathy, nephropathy and neuropathy. The typical histological changes of microvascular lesions are capillary basement membrane thickening, capillary occlusion and degeneration, eventually capillary dysfunction and organ ischemia. Therefore, we hypothesize that DM might induce local microvascular dysfunction and prostate ischemia, which prevent initiation and development of CaP. Currently, numerous studies showing effect of anti-angiogenesis therapy on CaP strongly support our hypothesis.
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PMID:Why does diabetes offer protective effects against prostate cancer? The possible role of its microvascular complications. 2131 65


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