From: Subject: Efaproxiral red blood cell concentration predicts efficacy in patients with brain metastases Date: Sun, 25 Jun 2006 11:01:11 +0200 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_0025_01C69846.AB872010" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.2869 This is a multi-part message in MIME format. ------=_NextPart_000_0025_01C69846.AB872010 Content-Type: text/html; charset="iso-8859-1" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.nature.com/bjc/journal/v94/n12/abs/6603169a.html;jsessionid=F36AF69FAEFA786FA5F4916FA32B8575 Efaproxiral red blood cell concentration predicts = efficacy in patients with brain metastases
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British Journal of Cancer (2006) = 94,=20 1777-1784. =
doi:10.1038/sj.bjc.6603169=20

Efaproxiral red blood = cell=20 concentration predicts efficacy in patients with brain=20 metastases

B = Stea1, E=20 Shaw2, T Pint=E9r3, J Hackman4, M = Craig4, J May4, R P Steffen4 and = J H=20 Suh5

1Department=20 of Radiation Oncology, The University of Arizona Health Sciences = Center,=20 1501 North Campbell Avenue, Tucson, AZ 85724, = USA

2Radiation Oncology Department, Wake = Forest=20 University School of Medicine, Medical Center Boulevard, = Winston-Salem, NC=20 27157, USA

3Department of=20 Oncology, Petz Alald=E1r Hospital of Gyor-Moson-Sopron County, = Zrinyi.u.13,=20 Gyor H-9024, Hungary

4Allos=20 Therapeutics Inc., 11080 CirclePoint Road, Suite 200, Westminster, = CO=20 80020, USA

5Cleveland=20 Clinic Foundation, Department of Radiation Oncology, Brain Tumor=20 Institute, T28, 9500 Euclid Avenue, Cleveland, OH 44195,=20 USA

3D""=20

Correspondence to: Dr B Stea, E-mail: bstea@azcc.arizona.edu

= Received=20 1 March 2006; revised 18 April 2006; accepted 19 April=20 2006

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Efaproxiral = (Efaproxyn=D4, RSR13), a synthetic allosteric modifier = of=20 haemoglobin (Hb), decreases Hb-oxygen (O2) binding = affinity and=20 enhances oxygenation of hypoxic tumours during radiation therapy. = This=20 analysis evaluated the Phase 3, Radiation Enhancing Allosteric = Compound=20 for Hypoxic Brain Metastases; RT-009 (REACH) study efficacy = results in=20 relation to efaproxiral exposure (efaproxiral red blood cell = concentration=20 (E-RBC) and number of doses). Recursive partitioning analysis = Class I or=20 II patients with brain metastases from solid tumours received = standard=20 whole-brain radiation therapy (3 Gy/fraction=20 =B4 10 days), plus supplemental = O2 (4=20 l/min), either with efaproxiral (75 or = 100=20 mg/kg daily) or without (control). = Efaproxiral=20 red blood cell concentrations were linearly extrapolated to all=20 efaproxiral doses received. Three patient populations were = analysed: (1)=20 all eligible, (2) non-small-cell lung cancer (NSCLC) as primary = cancer,=20 and (3) breast cancer primary. Efficacy endpoints were survival = and=20 response rate. Brain metastases patients achieving sufficient = E-RBC (483 3Dmu=20g/ml) and = receiving at=20 least seven of 10 efaproxiral doses were most likely to experience = survival and response benefits. Patients with breast cancer = primary=20 tumours generally achieved the target efaproxiral exposure and = therefore=20 gained greater benefit from efaproxiral treatment than NSCLC = patients.=20 This analysis defined the efaproxiral concentration-dependence in = survival=20 and response rate improvement, and provided a clearer = understanding of=20 efaproxiral dosing requirements.

Keywords: efaproxiral; RSR13; whole-brain = radiation=20 therapy; brain metastases; breast cancer; radiation=20 sensitiser

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Print ISSN: 0007-0920 | Online = ISSN:=20 1532-1827 =A9 2006 Cancer Research = UK
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10px; COLOR: #330066; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif; TEXT-DECORATION: none } A.searchbar:link { FONT-WEIGHT: bold; FONT-SIZE: 10px; COLOR: #330066; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif; TEXT-DECORATION: none } A.searchbar:visited { FONT-WEIGHT: bold; FONT-SIZE: 10px; COLOR: #330066; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif; TEXT-DECORATION: none } A.searchbar:hover { COLOR: #000000 } INPUT { FONT-SIZE: 10px; FONT-FAMILY: Verdana, Arial, Helvetica, sans-serif } TEXTAREA { FONT-SIZE: 10px; FONT-FAMILY: Verdana, Arial, Helvetica, sans-serif } SELECT { FONT-SIZE: 10px; FONT-FAMILY: Verdana, Arial, Helvetica, sans-serif } OPTION { FONT-SIZE: 10px; FONT-FAMILY: Verdana, Arial, Helvetica, sans-serif } FORM { PADDING-RIGHT: 0px; PADDING-LEFT: 0px; PADDING-BOTTOM: 0px; = PADDING-TOP: 0px } .date { FONT-SIZE: 10px; COLOR: #330066; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif } .issn { FONT-WEIGHT: bold; FONT-SIZE: 10px; COLOR: #330066; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif } .copyright { FONT-WEIGHT: bold; FONT-SIZE: 10px; COLOR: #666666; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif; TEXT-DECORATION: none } A.copyright:link { FONT-WEIGHT: bold; FONT-SIZE: 10px; COLOR: #666666; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif; TEXT-DECORATION: none } A.copyright:visited { FONT-WEIGHT: bold; FONT-SIZE: 10px; COLOR: #666666; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif; TEXT-DECORATION: none } A.copyright:hover { TEXT-DECORATION: underline } .navheader { FONT-WEIGHT: bold; FONT-SIZE: 11px; COLOR: #ffffff; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif } .nav { FONT-SIZE: 11px; COLOR: #000000; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif; TEXT-DECORATION: none } A.nav:link { FONT-SIZE: 11px; COLOR: #000000; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif; TEXT-DECORATION: none } A.nav:visited { FONT-SIZE: 11px; COLOR: #000000; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif; TEXT-DECORATION: none } A.nav:hover { COLOR: #663399 } .navon { FONT-WEIGHT: bold; FONT-SIZE: 11px; COLOR: #000000; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif; TEXT-DECORATION: none } A.navon:link { FONT-WEIGHT: bold; FONT-SIZE: 11px; COLOR: #000000; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif; TEXT-DECORATION: none } A.navon:visited { FONT-WEIGHT: bold; FONT-SIZE: 11px; COLOR: #000000; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif; TEXT-DECORATION: none } A.navon:hover { FONT-WEIGHT: bold; FONT-SIZE: 11px; COLOR: #000000; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif; TEXT-DECORATION: none } .free { FONT-SIZE: 11px; COLOR: #330066; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif; TEXT-DECORATION: none } .smallnav { FONT-SIZE: 10px; COLOR: #000000; LINE-HEIGHT: 14px; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif; TEXT-DECORATION: none } A.smallnav:link { FONT-SIZE: 10px; COLOR: #000000; LINE-HEIGHT: 14px; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif; TEXT-DECORATION: none } A.smallnav:visited { FONT-SIZE: 10px; COLOR: #000000; LINE-HEIGHT: 14px; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif; TEXT-DECORATION: none } A.smallnav:hover { COLOR: #663399 } .mednav { FONT-SIZE: 11px; COLOR: #000000; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif; TEXT-DECORATION: none } A.mednav:link { FONT-SIZE: 11px; COLOR: #000000; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif; TEXT-DECORATION: none } A.mednav:visited { FONT-SIZE: 11px; COLOR: #000000; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif; TEXT-DECORATION: none } A.mednav:hover { COLOR: #663399 } .bluenav { FONT-SIZE: 11px; COLOR: #663399; LINE-HEIGHT: 18px; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif; TEXT-DECORATION: none } A.bluenav:link { FONT-SIZE: 11px; COLOR: #663399; LINE-HEIGHT: 18px; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif; TEXT-DECORATION: none } A.bluenav:visited { FONT-SIZE: 11px; COLOR: #663399; LINE-HEIGHT: 18px; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif; TEXT-DECORATION: none } A.bluenav:hover { TEXT-DECORATION: underline } .greynav { FONT-SIZE: 11px; COLOR: #666666; LINE-HEIGHT: 18px; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif; TEXT-DECORATION: none } A.greynav:link { FONT-SIZE: 11px; COLOR: #666666; LINE-HEIGHT: 18px; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif; TEXT-DECORATION: none } A.greynav:visited { FONT-SIZE: 11px; COLOR: #666666; LINE-HEIGHT: 18px; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif; TEXT-DECORATION: none } A.greynav:hover { TEXT-DECORATION: underline } .smallbluenav { FONT-SIZE: 10px; COLOR: #663399; LINE-HEIGHT: 14px; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif; TEXT-DECORATION: none } A.smallbluenav:link { FONT-SIZE: 10px; COLOR: #663399; LINE-HEIGHT: 14px; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif; TEXT-DECORATION: none } A.smallbluenav:visited { FONT-SIZE: 10px; COLOR: #663399; LINE-HEIGHT: 14px; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif; TEXT-DECORATION: none } A.smallbluenav:hover { TEXT-DECORATION: underline } .head1 { FONT-WEIGHT: bold; FONT-SIZE: 16px; COLOR: #310063; LINE-HEIGHT: 18px; = FONT-FAMILY: Verdana, Arial, Helvetica, sans-serif } H1 { FONT-WEIGHT: bold; FONT-SIZE: 16px; COLOR: #310063; LINE-HEIGHT: 18px; = FONT-FAMILY: Verdana, Arial, Helvetica, sans-serif } .toollink { FONT-SIZE: 10px; COLOR: #999999; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif; TEXT-DECORATION: none } A.toollink:link { FONT-SIZE: 10px; COLOR: #999999; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif; TEXT-DECORATION: none } A.toollink:visited { FONT-SIZE: 10px; COLOR: #999999; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif; TEXT-DECORATION: none } A.toollink:hover { COLOR: #310063 } .introtextblue { FONT-SIZE: 11px; COLOR: #330066; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif; TEXT-DECORATION: none } .introtext { FONT-SIZE: 11px; COLOR: #000000; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif; TEXT-DECORATION: none } .medtext { FONT-SIZE: 11px; COLOR: #000000; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif; TEXT-DECORATION: none } .featured { FONT-SIZE: 13px; COLOR: #310063; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif; TEXT-DECORATION: none } .archivelink { FONT-SIZE: 12px; COLOR: #0000ff; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif; TEXT-DECORATION: underline } .headline { FONT-WEIGHT: bold; FONT-SIZE: 12px; COLOR: #310063; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif } .text { FONT-SIZE: 10px; COLOR: #000000; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif; TEXT-DECORATION: none } .smalltext { FONT-SIZE: 8px; COLOR: #000000; FONT-FAMILY: Verdana, Arial, Helvetica, = sans-serif; TEXT-DECORATION: none } ------=_NextPart_000_0025_01C69846.AB872010 Content-Type: text/css; charset="iso-8859-1" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.nature.com/bjc/style_article_older.css BODY { FONT-SIZE: small; COLOR: #000000; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif } .body { FONT-SIZE: small; COLOR: #000000; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif } .bodytext { FONT-SIZE: small; COLOR: #000000; LINE-HEIGHT: 133%; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif } .tablehead { FONT-WEIGHT: bold; FONT-SIZE: small; COLOR: #000000; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif } .tablecell { FONT-SIZE: small; COLOR: #000000; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif } .tableline { BACKGROUND-COLOR: #000000 } .articletitle { FONT-WEIGHT: bold; FONT-SIZE: 105%; COLOR: #000000; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif } .smalltext { FONT-SIZE: xx-small; COLOR: #000000; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif } .smallgrey { FONT-SIZE: xx-small; COLOR: #666666; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif } .smallblue { FONT-SIZE: xx-small; COLOR: #663399; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif } .smalllink { FONT-SIZE: x-small; COLOR: #0000ff; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif; TEXT-DECORATION: underline } A.smalllink:link { FONT-SIZE: x-small; COLOR: #0000ff; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif; TEXT-DECORATION: underline } A.smalllink:hover { COLOR: #663399 } A.smalllink:visited { COLOR: #663399 } .head2 { FONT-WEIGHT: bold; FONT-SIZE: 105%; COLOR: #663399; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif } H2 { FONT-WEIGHT: bold; FONT-SIZE: 105%; COLOR: #663399; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif } .head3 { FONT-WEIGHT: bold; FONT-SIZE: small; COLOR: #663399; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif; TEXT-DECORATION: none } H3 { FONT-WEIGHT: bold; FONT-SIZE: small; COLOR: #663399; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif; TEXT-DECORATION: none } A.head3:hover { TEXT-DECORATION: underline } .head4 { FONT-WEIGHT: bold; FONT-SIZE: small; COLOR: #663399; FONT-STYLE: = italic; FONT-FAMILY: Verdana, Arial, Helvetica, sans-serif; = TEXT-DECORATION: none } H4 { FONT-WEIGHT: bold; FONT-SIZE: small; COLOR: #663399; FONT-STYLE: = italic; FONT-FAMILY: Verdana, Arial, Helvetica, sans-serif; = TEXT-DECORATION: none } .legend { FONT-SIZE: x-small; COLOR: #000000; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif } .tabfn { FONT-SIZE: x-small; COLOR: #000000; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif } .reftext { FONT-SIZE: x-small; COLOR: #000000; LINE-HEIGHT: 133%; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif } ------=_NextPart_000_0025_01C69846.AB872010 Content-Type: text/css; charset="iso-8859-1" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.nature.com/bjc/style_article.css BODY { FONT-SIZE: 11px; COLOR: #000000; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif } .body { FONT-SIZE: 11px; COLOR: #000000; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif } .bodytext { FONT-SIZE: x-small; COLOR: #000000; LINE-HEIGHT: 133%; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif } .tablehead { FONT-WEIGHT: bold; FONT-SIZE: x-small; COLOR: #000000; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif } .tablecell { FONT-SIZE: x-small; COLOR: #000000; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif } .tableline { BACKGROUND-COLOR: #000000 } .articletitle { FONT-WEIGHT: bold; FONT-SIZE: 110%; COLOR: #000000; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif } .smalltext { FONT-SIZE: 10px; COLOR: #000000; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif } .smallgrey { FONT-SIZE: xx-small; COLOR: #666666; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif } .smallblue { FONT-SIZE: xx-small; COLOR: #663399; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif } .smalllink { FONT-SIZE: xx-small; COLOR: #0000ff; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif; TEXT-DECORATION: underline } A.smalllink:link { FONT-SIZE: xx-small; COLOR: #0000ff; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif; TEXT-DECORATION: underline } A.smalllink:hover { COLOR: #310063 } A.smalllink:visited { COLOR: #310063 } .head2 { FONT-WEIGHT: bold; FONT-SIZE: 110%; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif } H2 { FONT-WEIGHT: bold; FONT-SIZE: 110%; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif } .head3 { FONT-WEIGHT: bold; FONT-SIZE: 11px; COLOR: #310063; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif; TEXT-DECORATION: none } H3 { FONT-WEIGHT: bold; FONT-SIZE: 11px; COLOR: #310063; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif; TEXT-DECORATION: none } A.head3:hover { TEXT-DECORATION: underline } .head4 { FONT-WEIGHT: bold; FONT-SIZE: x-small; COLOR: #310063; FONT-STYLE: = italic; FONT-FAMILY: Verdana, Arial, Helvetica, sans-serif; = TEXT-DECORATION: none } H4 { FONT-WEIGHT: bold; FONT-SIZE: x-small; COLOR: #310063; FONT-STYLE: = italic; FONT-FAMILY: Verdana, Arial, Helvetica, sans-serif; = TEXT-DECORATION: none } .legend { FONT-SIZE: xx-small; COLOR: #000000; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif } .tabfn { FONT-SIZE: xx-small; COLOR: #000000; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif } .reftext { FONT-SIZE: x-small; COLOR: #000000; LINE-HEIGHT: 133%; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif } .linker { FONT-WEIGHT: bold; FONT-SIZE: 110%; COLOR: #0000ff; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif } ------=_NextPart_000_0025_01C69846.AB872010 Content-Type: text/css; charset="iso-8859-1" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.nature.com/bjc/style.css .searchbar { FONT-WEIGHT: bold; FONT-SIZE: 10px; COLOR: #330066; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif; TEXT-DECORATION: none } A.searchbar:link { FONT-WEIGHT: bold; FONT-SIZE: 10px; COLOR: #330066; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif; TEXT-DECORATION: none } A.searchbar:visited { FONT-WEIGHT: bold; FONT-SIZE: 10px; COLOR: #330066; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif; TEXT-DECORATION: none } A.searchbar:hover { COLOR: #000000 } INPUT { FONT-SIZE: 10px; FONT-FAMILY: Verdana, Arial, Helvetica, sans-serif } TEXTAREA { FONT-SIZE: 10px; FONT-FAMILY: Verdana, Arial, Helvetica, sans-serif } SELECT { FONT-SIZE: 10px; FONT-FAMILY: Verdana, Arial, Helvetica, sans-serif } OPTION { FONT-SIZE: 10px; FONT-FAMILY: Verdana, Arial, Helvetica, sans-serif } FORM { PADDING-RIGHT: 0px; PADDING-LEFT: 0px; PADDING-BOTTOM: 0px; = PADDING-TOP: 0px } .date { FONT-SIZE: 10px; COLOR: #330066; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif } .issn { FONT-WEIGHT: bold; FONT-SIZE: 10px; COLOR: #330066; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif } .copyright { FONT-WEIGHT: bold; FONT-SIZE: 10px; COLOR: #666666; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif; TEXT-DECORATION: none } A.copyright:link { FONT-WEIGHT: bold; FONT-SIZE: 10px; COLOR: #666666; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif; TEXT-DECORATION: none } A.copyright:visited { FONT-WEIGHT: bold; FONT-SIZE: 10px; COLOR: #666666; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif; TEXT-DECORATION: none } A.copyright:hover { TEXT-DECORATION: underline } .navheader { FONT-WEIGHT: bold; FONT-SIZE: 11px; COLOR: #ffffff; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif } .nav { FONT-SIZE: 11px; COLOR: #000000; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif; TEXT-DECORATION: none } A.nav:link { FONT-SIZE: 11px; COLOR: #000000; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif; TEXT-DECORATION: none } A.nav:visited { FONT-SIZE: 11px; COLOR: #000000; FONT-FAMILY: Verdana, Arial, = Helvetica, sans-serif; TEXT-DECORATION: none } A.nav:hover { COLOR: #663399 } .navon { FONT-WEIGHT: bold; FONT-SIZE: 11px; COLOR: #000000; FONT-FAMILY: = Verdana, Arial, Helvetica, sans-serif; TEXT-DECORATION: none } A.navon:link { FONT-WEIGHT: bold; FONT-SIZE: 11px; COLOR: #000000; FONT-FAMILY: = Verdana, Arial, Helvetica, 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