@prefix rdf: . @prefix ns1: . rdf:type ns1:RelevantPaper , ns1:ReferencePaper , ns1:CitationPaper . @prefix rdfs: . rdfs:seeAlso , , , . @prefix bibo: . bibo:cites , , , , , , , , , , , , , , , , , ; ns1:cocitationWith , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ; ns1:hasRelevantBibliographicResourceOf _:b268208144 , _:b268208145 , _:b268208146 , _:b268208147 , _:b268208148 , _:b268208136 , _:b268208137 , _:b268208138 , _:b268208139 , _:b268208140 , _:b268208141 , _:b268208142 , _:b268208143 , _:b268208128 , _:b268208129 , _:b268208130 , _:b268208131 , _:b268208132 , _:b268208133 , _:b268208134 , _:b268208135 , _:b268208120 , _:b268208121 , _:b268208122 , _:b268208123 , _:b268208124 , _:b268208125 , _:b268208126 , _:b268208127 , _:b268208112 , _:b268208113 , _:b268208114 , _:b268208115 , _:b268208116 , _:b268208117 , _:b268208118 , _:b268208119 , _:b268208108 , _:b268208109 , _:b268208110 , _:b268208111 ; ns1:pmcid "PMC0" ; bibo:doi "10.1038%2Fsj.bjc.6600817" . @prefix ns4: . ns4:contains _:b478054 , _:b478030 . _:b478030 rdf:type ns4:Section . @prefix dc: . _:b478030 dc:title "discussion" ; ns4:contains _:b478044 , _:b478045 , _:b478046 , _:b478047 , _:b478040 , _:b478041 , _:b478042 , _:b478043 , _:b478036 , _:b478037 , _:b478038 , _:b478039 , _:b478032 , _:b478033 , _:b478034 , _:b478035 , _:b478031 , _:b478052 , _:b478053 , _:b478048 , _:b478049 , _:b478050 , _:b478051 . _:b478031 rdf:type ns1:Context ; rdf:value "A recent clinical trial of thalidomide for androgen-independent prostate cancer randomised patients to a low-dose arm of 200\u2009mg daily, or a high-dose arm, escalating to the highest tolerated dose (up to 1200\u2009mg) (Figg et al, >>2001<<). In all, 15% of patients showed a PSA decline of over 50%, and 28% showed a decline of at least 40%, all of whom were in the low-dose arm (Figg et al, 2001)." ; ns1:mentions . _:b478032 rdf:type ns1:Context ; rdf:value "In all, 15% of patients showed a PSA decline of over 50%, and 28% showed a decline of at least 40%, all of whom were in the low-dose arm (Figg et al, >>2001<<). Higher doses appeared to result in loss of efficacy, perhaps reflecting the known immunosuppressive effects of thalidomide, which may facilitate disease progression. Our data indicate that similar effects on serum PSA are seen at an" ; ns1:mentions . _:b478033 rdf:type ns1:Context ; rdf:value "PSA has been proposed as a tumour marker for prostate adenocarcinoma, the levels providing an indication of disease volume and biological activity, such that a fall in PSA indicates a potential beneficial effect (Kelly et al, >>1993<<; Sartor et al, 1998)." ; ns1:mentions . _:b478034 rdf:type ns1:Context ; rdf:value "proposed as a tumour marker for prostate adenocarcinoma, the levels providing an indication of disease volume and biological activity, such that a fall in PSA indicates a potential beneficial effect (Kelly et al, 1993; Sartor et al, >>1998<<). However, it should be remembered that selection of disease markers is a problem in clinical trials for metastatic prostate cancer (Morris and Scher, 2002)." ; ns1:mentions . _:b478035 rdf:type ns1:Context ; rdf:value "However, it should be remembered that selection of disease markers is a problem in clinical trials for metastatic prostate cancer (Morris and Scher, >>2002<<). As recommended by the guidelines of the Prostate-Specific Antigen Working Group (Bubley et al, 1999), a decline in serum PSA of at least 50% without clinical evidence of progression was employed as the main outcome measure in the" ; ns1:mentions . _:b478036 rdf:type ns1:Context ; rdf:value "As recommended by the guidelines of the Prostate-Specific Antigen Working Group (Bubley et al, >>1999<<), a decline in serum PSA of at least 50% without clinical evidence of progression was employed as the main outcome measure in the current study." ; ns1:mentions . _:b478037 rdf:type ns1:Context ; rdf:value "velocity suggests clinical benefit, it is still debated how much of a decline is significant and its precise implication, while radiological assessment of metastatic disease is insensitive and difficult to interpret (Morris and Scher, >>2002<<)." ; ns1:mentions . _:b478038 rdf:type ns1:Context ; rdf:value "Thalidomide has been observed to increase PSA expression in a prostate cancer cell line in vitro (Dixon et al, >>1999<<), so the PSA reduction observed in some patients probably reflects a differing effect on tumours in vivo." ; ns1:mentions . _:b478039 rdf:type ns1:Context ; rdf:value "Thalidomide is known to reduce angiogenic activity through selective inhibition of bFGF (D'Amato et al, >>1994<<) and tumour-associated macrophages (Joseph and Isaacs, 1998)." ; ns1:mentions . _:b478040 rdf:type ns1:Context ; rdf:value "Thalidomide is known to reduce angiogenic activity through selective inhibition of bFGF (D'Amato et al, 1994) and tumour-associated macrophages (Joseph and Isaacs, >>1998<<). Since angiogenesis is important in the development and metastasis of solid tumours in general (Folkman, 1971) and it is a negative prognostic marker in prostate cancer specifically (Eckhardt and Pluda, 1997), this may reflect the" ; ns1:mentions . _:b478041 rdf:type ns1:Context ; rdf:value "Since angiogenesis is important in the development and metastasis of solid tumours in general (Folkman, >>1971<<) and it is a negative prognostic marker in prostate cancer specifically (Eckhardt and Pluda, 1997), this may reflect the mechanism by which thalidomide is acting in androgen-independent prostate cancer." ; ns1:mentions . _:b478042 rdf:type ns1:Context ; rdf:value "Since angiogenesis is important in the development and metastasis of solid tumours in general (Folkman, 1971) and it is a negative prognostic marker in prostate cancer specifically (Eckhardt and Pluda, >>1997<<), this may reflect the mechanism by which thalidomide is acting in androgen-independent prostate cancer." ; ns1:mentions . _:b478043 rdf:type ns1:Context ; rdf:value "Peripheral neuropathy is a recognised complication of thalidomide (Tseng et al, >>1996<<), with older persons at greater risk (Ochonisky et al, 1994)." ; ns1:mentions . _:b478044 rdf:type ns1:Context ; rdf:value "Peripheral neuropathy is a recognised complication of thalidomide (Tseng et al, 1996), with older persons at greater risk (Ochonisky et al, >>1994<<). We demonstrated that nine out of 13 patients in this study, including four of the seven men who were on treatment for 6 months, had a \u2018para-neoplastic neuropathy\u2019 at screening, which has previously been reported in association with" ; ns1:mentions . _:b478045 rdf:type ns1:Context ; rdf:value "13 patients in this study, including four of the seven men who were on treatment for 6 months, had a \u2018para-neoplastic neuropathy\u2019 at screening, which has previously been reported in association with prostate cancer (Lucchinetti et al, >>1998<<). By the end of the study, all patients tested had a sensory neuropathy on NCS, and would have had to discontinue treatment on the basis of safety recommendations in the presence of a 50% decrease in measured parameters (Gardner-Medwin et" ; ns1:mentions . _:b478046 rdf:type ns1:Context ; rdf:value "end of the study, all patients tested had a sensory neuropathy on NCS, and would have had to discontinue treatment on the basis of safety recommendations in the presence of a 50% decrease in measured parameters (Gardner-Medwin et al, >>1994<<). While thalidomide is a potential contributory factor, the para-neoplastic neuropathy seen in the majority of screened patients may have emerged further during the study period." ; ns1:mentions . _:b478047 rdf:type ns1:Context ; rdf:value "in androgen-independent prostate cancer has been reported previously in a study that also recorded onset of symptomatic peripheral neuropathy in six out of 67 patients receiving a daily dose of at least 200\u2009mg (Molloy et al, >>2001<<). In this study, six out of eight men treated for 6 months and all three men treated for 9 months developed a neuropathy." ; ns1:mentions . _:b478048 rdf:type ns1:Context ; rdf:value "Further reported adverse effects of thalidomide include constipation, headache, nausea, weight gain, oedema, transient rashes and somnolence (Tseng et al, >>1996<<). These effects are generally minor. Neither the SF 36 nor the ICS male questionnaire scores showed any significant change in the current study." ; ns1:mentions . _:b478049 rdf:type ns1:Context ; rdf:value "Scores on the calculated SF 36 scales at screening were worse than values for healthy men of equivalent age (Brazier et al, >>1992<<; Ware et al, 1993), or men with benign prostatic hyperplasia and hypertension (Ware et al, 1993)." ; ns1:mentions . _:b478050 rdf:type ns1:Context ; rdf:value "It was granted FDA approval in the USA in 1998, for use in cutaneous manifestations of leprosy, under controls requiring counselling and detailed consent (Zeldis et al, >>1999<<)." ; ns1:mentions . _:b478051 rdf:type ns1:Context ; rdf:value "Most angiogenesis-inhibiting agents are cytostatic and theoretically could provide additional benefit in combination with other chemotherapeutic agents, particularly where the overall tumour burden is low (Figg et al, >>2001<<). A reduction in serum PSA of at least 50%, as seen in three men in the current study, may predict a relatively prolonged survival (Kelly et al, 1993; Sartor et al, 1998). Consequently, low-dose thalidomide may have potential as an" ; ns1:mentions . _:b478052 rdf:type ns1:Context ; rdf:value "A reduction in serum PSA of at least 50%, as seen in three men in the current study, may predict a relatively prolonged survival (Kelly et al, >>1993<<; Sartor et al, 1998)." ; ns1:mentions . _:b478053 rdf:type ns1:Context ; rdf:value "A reduction in serum PSA of at least 50%, as seen in three men in the current study, may predict a relatively prolonged survival (Kelly et al, 1993; Sartor et al, >>1998<<). Consequently, low-dose thalidomide may have potential as an adjunct to hormonal manipulation and other agents in therapy of poor prognosis or advanced prostate cancer, although further work is required to identify those likely to" ; ns1:mentions . _:b478054 rdf:type ns4:Section ; dc:title "material and methods" ; ns4:contains _:b478056 , _:b478057 , _:b478055 . _:b478055 rdf:type ns1:Context ; rdf:value "Thus all patients had progressive disease on biochemical criteria (Bubley et al, >>1999<<). Exclusion criteria included any unstable medical condition, long-term corticosteroid therapy, surgery or radiotherapy in the preceding 28 days, spinal cord compression or severe bone pain requiring immediate treatment. No patient had" ; ns1:mentions . _:b478056 rdf:type ns1:Context ; rdf:value "using bilateral lower limb recording of the response amplitude and conduction velocity from two sensory (sural and superficial peroneal) and two motor (common peroneal and posterior tibial) nerves (Johnsen and Fuglsang-Fredericksen, >>2000<<). All of the sensory nerve action potential (SNAP) data were pooled for analysis." ; ns1:mentions . _:b478057 rdf:type ns1:Context ; rdf:value "Patients showing a decline in serum PSA of at least 50% without clinical evidence of progression were considered to show a PSA response, according to the guidelines of the Prostate-Specific Antigen Working Group (Bubley et al, >>1999<<). In addition, PSA velocity was recorded, derived from the gradient of log plots of the PSA against time, prior to and following initiation of thalidomide. 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