Strict Standards: Non-static method SEBenchmark::getInstance() should not be called statically in /home3/nextron/public_html/header.php on line 35

Strict Standards: Non-static method SESmarty::getInstance() should not be called statically in /home3/nextron/public_html/header.php on line 43

Strict Standards: Non-static method SEDatabase::getInstance() should not be called statically in /home3/nextron/public_html/header.php on line 96

Strict Standards: Non-static method SELanguage::info() should not be called statically in /home3/nextron/public_html/header.php on line 104

Strict Standards: Non-static method SELanguage::_init() should not be called statically in /home3/nextron/public_html/include/language/language.php on line 334

Strict Standards: Non-static method SELanguageStorage::getInstance() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/language/language.php on line 156

Strict Standards: Declaration of SELanguageStorageMysql::edit() should be compatible with SELanguageStorage::edit() in /home3/nextron/public_html/include/language/storage/mysql.php on line 255

Strict Standards: Declaration of SELanguageStorageMysql::get() should be compatible with SELanguageStorage::get() in /home3/nextron/public_html/include/language/storage/mysql.php on line 255

Strict Standards: Non-static method SECore::getSettings() should not be called statically in /home3/nextron/public_html/header.php on line 107

Strict Standards: Non-static method SECache::getInstance() should not be called statically in /home3/nextron/public_html/include/class_core.php on line 28

Strict Standards: Non-static method SECacheStorage::getInstance() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/cache/cache.php on line 66

Strict Standards: Non-static method SEDatabase::getInstance() should not be called statically in /home3/nextron/public_html/include/class_core.php on line 39

Strict Standards: Non-static method SECache::getInstance() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/class_url.php on line 67

Strict Standards: Non-static method SECacheStorage::getInstance() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/cache/cache.php on line 66

Strict Standards: Non-static method SEDatabase::getInstance() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/class_url.php on line 78

Strict Standards: Non-static method SELanguage::_preload_multi() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/class_datetime.php on line 35

Strict Standards: Non-static method SELanguage::_init() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/language/language.php on line 529

Strict Standards: Non-static method SESession::getInstance() should not be called statically in /home3/nextron/public_html/header.php on line 125

Strict Standards: Non-static method SESessionStorage::getInstance() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/session/session.php on line 49

Strict Standards: Declaration of SESessionStorageNone::register() should be compatible with SESessionStorage::register($options = Array) in /home3/nextron/public_html/include/session/storage/none.php on line 16

Strict Standards: Non-static method SEDatabase::getInstance() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/session/session.php on line 600

Strict Standards: Non-static method SESession::getInstance() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/class_user.php on line 509

Strict Standards: Non-static method SESession::getInstance() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/class_admin.php on line 208

Strict Standards: Non-static method SELanguage::select() should not be called statically in /home3/nextron/public_html/header.php on line 181

Strict Standards: Non-static method SELanguage::_init() should not be called statically in /home3/nextron/public_html/include/language/language.php on line 234

Strict Standards: Non-static method SELanguage::info() should not be called statically in /home3/nextron/public_html/header.php on line 183

Strict Standards: Non-static method SELanguage::_init() should not be called statically in /home3/nextron/public_html/include/language/language.php on line 334

Strict Standards: Non-static method SELanguage::info() should not be called statically in /home3/nextron/public_html/header.php on line 189

Strict Standards: Non-static method SELanguage::_init() should not be called statically in /home3/nextron/public_html/include/language/language.php on line 334

Strict Standards: Non-static method SECore::getPlugins() should not be called statically in /home3/nextron/public_html/header.php on line 229

Strict Standards: Non-static method SECache::getInstance() should not be called statically in /home3/nextron/public_html/include/class_core.php on line 62

Strict Standards: Non-static method SECacheStorage::getInstance() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/cache/cache.php on line 66

Strict Standards: Non-static method SEDatabase::getInstance() should not be called statically in /home3/nextron/public_html/include/class_core.php on line 73

Strict Standards: Declaration of rc_rssfeed::delete() should be compatible with rc_model::delete($id = NULL) in /home3/nextron/public_html/include/class_rssfeed.php on line 132

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 720

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 1087

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 1595

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 1636

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 1656

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 1756

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 1960

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 2358

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 2362

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 2366

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 2370

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 2418

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 2440

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 2445

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 2449

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 2453

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 2501

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 2523

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 2927

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 2935

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 2943

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 2951

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 2959

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 3300

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 3304

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 3308

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 3312

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 3373

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 3395

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 3434

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 3456

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 3461

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 3465

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 3469

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 3473

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 3783

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 3815

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 3845

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 3868

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 3879

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 3889

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 3911

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 3925

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 3952

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 3978

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 4167

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 4180

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 4201

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 4214

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 4242

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 4256

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 4278

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 4292

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 4496

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 4532

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 4568

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 4594

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 4623

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 4637

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 4668

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 4698

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 4851

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 4876

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 4908

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 4934

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 4988

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 5117

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 5153

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 5186

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 5217

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 5321

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 5353

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 5392

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 5428

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 5463

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 5498

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 5505

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 5790

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 5794

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 5798

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 5802

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 5850

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 5872

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 5877

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 5881

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 5885

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 5933

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 5955

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 6392

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 7588

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 7649

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 7730

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 12921

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 12986

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 13011

Deprecated: Assigning the return value of new by reference is deprecated in /home3/nextron/public_html/include/class_radcodes_rss.php on line 13574

Strict Standards: Non-static method SELanguage::_preload_multi() should not be called statically in /home3/nextron/public_html/header_rssfeed.php on line 10

Strict Standards: Non-static method SELanguage::_init() should not be called statically in /home3/nextron/public_html/include/language/language.php on line 529

Strict Standards: Non-static method rc_toolkit::get_setting() should not be called statically in /home3/nextron/public_html/header_rssfeed.php on line 14

Strict Standards: Non-static method rc_toolkit::owner_level() should not be called statically in /home3/nextron/public_html/header_rssfeed.php on line 25

Strict Standards: Non-static method SELanguage::_preload_multi() should not be called statically in /home3/nextron/public_html/header_article.php on line 10

Strict Standards: Non-static method SELanguage::_init() should not be called statically in /home3/nextron/public_html/include/language/language.php on line 529

Strict Standards: Non-static method SE_Hook::register() should not be called statically in /home3/nextron/public_html/header_article.php on line 66

Strict Standards: Non-static method SE_Hook::create() should not be called statically in /home3/nextron/public_html/include/class_hook.php on line 151

Strict Standards: Non-static method SE_Hook::register() should not be called statically in /home3/nextron/public_html/header_article.php on line 67

Strict Standards: Non-static method SE_Hook::create() should not be called statically in /home3/nextron/public_html/include/class_hook.php on line 151

Strict Standards: Non-static method SELanguage::_preload() should not be called statically in /home3/nextron/public_html/header_event.php on line 15

Strict Standards: Non-static method SELanguage::_init() should not be called statically in /home3/nextron/public_html/include/language/language.php on line 559

Strict Standards: Non-static method SE_Hook::register() should not be called statically in /home3/nextron/public_html/header_event.php on line 67

Strict Standards: Non-static method SE_Hook::create() should not be called statically in /home3/nextron/public_html/include/class_hook.php on line 151

Strict Standards: Non-static method SE_Hook::register() should not be called statically in /home3/nextron/public_html/header_event.php on line 69

Strict Standards: Non-static method SE_Hook::create() should not be called statically in /home3/nextron/public_html/include/class_hook.php on line 151

Strict Standards: Non-static method SE_Hook::register() should not be called statically in /home3/nextron/public_html/header_event.php on line 71

Strict Standards: Non-static method SE_Hook::create() should not be called statically in /home3/nextron/public_html/include/class_hook.php on line 151

Strict Standards: Non-static method SE_Hook::register() should not be called statically in /home3/nextron/public_html/header_event.php on line 73

Strict Standards: Non-static method SE_Hook::create() should not be called statically in /home3/nextron/public_html/include/class_hook.php on line 151

Strict Standards: Non-static method SE_Hook::register() should not be called statically in /home3/nextron/public_html/header_event.php on line 75

Strict Standards: Non-static method SE_Hook::create() should not be called statically in /home3/nextron/public_html/include/class_hook.php on line 151

Strict Standards: Non-static method SELanguage::_preload() should not be called statically in /home3/nextron/public_html/header_group.php on line 14

Strict Standards: Non-static method SELanguage::_init() should not be called statically in /home3/nextron/public_html/include/language/language.php on line 559

Strict Standards: Non-static method SE_Hook::register() should not be called statically in /home3/nextron/public_html/header_group.php on line 82

Strict Standards: Non-static method SE_Hook::create() should not be called statically in /home3/nextron/public_html/include/class_hook.php on line 151

Strict Standards: Non-static method SE_Hook::register() should not be called statically in /home3/nextron/public_html/header_group.php on line 85

Strict Standards: Non-static method SE_Hook::create() should not be called statically in /home3/nextron/public_html/include/class_hook.php on line 151

Strict Standards: Non-static method SE_Hook::register() should not be called statically in /home3/nextron/public_html/header_group.php on line 88

Strict Standards: Non-static method SE_Hook::create() should not be called statically in /home3/nextron/public_html/include/class_hook.php on line 151

Strict Standards: Non-static method SELanguage::_preload() should not be called statically in /home3/nextron/public_html/header_classified.php on line 15

Strict Standards: Non-static method SELanguage::_init() should not be called statically in /home3/nextron/public_html/include/language/language.php on line 559

Strict Standards: Non-static method SE_Hook::register() should not be called statically in /home3/nextron/public_html/header_classified.php on line 64

Strict Standards: Non-static method SE_Hook::create() should not be called statically in /home3/nextron/public_html/include/class_hook.php on line 151

Strict Standards: Non-static method SE_Hook::register() should not be called statically in /home3/nextron/public_html/header_classified.php on line 66

Strict Standards: Non-static method SE_Hook::create() should not be called statically in /home3/nextron/public_html/include/class_hook.php on line 151

Strict Standards: Non-static method SE_Hook::register() should not be called statically in /home3/nextron/public_html/header_classified.php on line 68

Strict Standards: Non-static method SE_Hook::create() should not be called statically in /home3/nextron/public_html/include/class_hook.php on line 151

Strict Standards: Non-static method SE_Hook::register() should not be called statically in /home3/nextron/public_html/header_radcodes.php on line 10

Strict Standards: Non-static method SE_Hook::create() should not be called statically in /home3/nextron/public_html/include/class_hook.php on line 151

Strict Standards: Non-static method SELanguage::_preload_multi() should not be called statically in /home3/nextron/public_html/header_vid.php on line 15

Strict Standards: Non-static method SELanguage::_init() should not be called statically in /home3/nextron/public_html/include/language/language.php on line 529

Strict Standards: Non-static method SE_Hook::register() should not be called statically in /home3/nextron/public_html/header_vid.php on line 44

Strict Standards: Non-static method SE_Hook::create() should not be called statically in /home3/nextron/public_html/include/class_hook.php on line 151

Strict Standards: Non-static method SE_Hook::register() should not be called statically in /home3/nextron/public_html/header_vid.php on line 45

Strict Standards: Non-static method SE_Hook::create() should not be called statically in /home3/nextron/public_html/include/class_hook.php on line 151

Strict Standards: Non-static method SELanguage::_preload_multi() should not be called statically in /home3/nextron/public_html/header_page.php on line 11

Strict Standards: Non-static method SELanguage::_init() should not be called statically in /home3/nextron/public_html/include/language/language.php on line 529

Strict Standards: Non-static method SELanguage::_preload_multi() should not be called statically in /home3/nextron/public_html/header_gmap.php on line 10

Strict Standards: Non-static method SELanguage::_init() should not be called statically in /home3/nextron/public_html/include/language/language.php on line 529

Strict Standards: Non-static method SE_Hook::exists() should not be called statically in /home3/nextron/public_html/header.php on line 298

Strict Standards: Non-static method SE_Hook::create() should not be called statically in /home3/nextron/public_html/include/class_hook.php on line 246

Strict Standards: Non-static method SECache::getInstance() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/class_user.php on line 280

Strict Standards: Non-static method SECacheStorage::getInstance() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/cache/cache.php on line 66

Strict Standards: Non-static method SEDatabase::getInstance() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/class_user.php on line 291

Strict Standards: Non-static method SECache::getInstance() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/class_user.php on line 320

Strict Standards: Non-static method SECacheStorage::getInstance() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/cache/cache.php on line 66

Strict Standards: Non-static method SEDatabase::getInstance() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/class_user.php on line 331

Strict Standards: Non-static method SECache::getInstance() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/class_user.php on line 200

Strict Standards: Non-static method SECacheStorage::getInstance() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/cache/cache.php on line 66

Strict Standards: Non-static method SEDatabase::getInstance() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/class_user.php on line 211

Strict Standards: Non-static method SECache::getInstance() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/class_user.php on line 240

Strict Standards: Non-static method SECacheStorage::getInstance() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/cache/cache.php on line 66

Strict Standards: Non-static method SEDatabase::getInstance() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/class_user.php on line 251

Strict Standards: Non-static method SELanguage::_preload() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/class_user.php on line 179

Strict Standards: Non-static method SELanguage::_init() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/language/language.php on line 559

Strict Standards: Non-static method SECore::getLanguages() should not be called statically in /home3/nextron/public_html/footer.php on line 14

Strict Standards: Non-static method SECache::getInstance() should not be called statically in /home3/nextron/public_html/include/class_core.php on line 96

Strict Standards: Non-static method SECacheStorage::getInstance() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/cache/cache.php on line 66

Strict Standards: Non-static method SELanguage::_languages() should not be called statically in /home3/nextron/public_html/include/class_core.php on line 110

Strict Standards: Non-static method SELanguage::_init() should not be called statically in /home3/nextron/public_html/include/language/language.php on line 366

Strict Standards: Non-static method SE_Hook::exists() should not be called statically in /home3/nextron/public_html/footer.php on line 29

Strict Standards: Non-static method SE_Hook::create() should not be called statically in /home3/nextron/public_html/include/class_hook.php on line 246

Strict Standards: Non-static method SE_Hook::exists() should not be called statically in /home3/nextron/public_html/footer.php on line 32

Strict Standards: Non-static method SE_Hook::create() should not be called statically in /home3/nextron/public_html/include/class_hook.php on line 246

Strict Standards: Non-static method SE_Hook::call() should not be called statically in /home3/nextron/public_html/footer.php on line 32

Strict Standards: Non-static method SE_Hook::create() should not be called statically in /home3/nextron/public_html/include/class_hook.php on line 272

Strict Standards: Non-static method SELanguage::info() should not be called statically in /home3/nextron/public_html/footer.php on line 58

Strict Standards: Non-static method SELanguage::_init() should not be called statically in /home3/nextron/public_html/include/language/language.php on line 334

Strict Standards: Non-static method SELanguage::_preload_multi() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/smarty/templates_c/%%86^861^861EA998%%article.tpl.php on line 6

Strict Standards: Non-static method SELanguage::_init() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/language/language.php on line 529

Strict Standards: Non-static method SELanguage::load() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/smarty/templates_c/%%86^861^861EA998%%article.tpl.php on line 7

Strict Standards: Non-static method SELanguage::_init() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/language/language.php on line 686

Strict Standards: Non-static method SELanguage::_init() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/language/storage.php on line 192

Strict Standards: Non-static method SECache::getInstance() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/language/storage.php on line 193

Strict Standards: Non-static method SECacheStorage::getInstance() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/cache/cache.php on line 66

Strict Standards: Only variables should be passed by reference in /home3/nextron/public_html/include/language/storage/mysql.php on line 177

Strict Standards: Non-static method SELanguage::_preload_multi() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/smarty/templates_c/%%05^053^053AB562%%header_article2.tpl.php on line 4

Strict Standards: Non-static method SELanguage::_init() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/language/language.php on line 529

Strict Standards: Non-static method SELanguage::load() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/smarty/templates_c/%%05^053^053AB562%%header_article2.tpl.php on line 5

Strict Standards: Non-static method SELanguage::_init() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/language/language.php on line 686

Strict Standards: Non-static method SELanguage::_init() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/language/storage.php on line 169

Strict Standards: Non-static method SECache::getInstance() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/language/storage.php on line 170

Strict Standards: Non-static method SECacheStorage::getInstance() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/cache/cache.php on line 66
Afinitor® shows potential to reverse resistance to Herceptin®[*] in metastatic breast cancer patients, leading to Phase III tria - <br /> <b>Strict Standards</b>: Non-static method SELanguage::_get() should not be called statically, assuming $this from incompatible context in <b>/home3/nextron/public_html/include/smarty/templates_c/%%05^053^053AB562%%header_article2.tpl.php</b> on line <b>16</b><br /> <br /> <b>Strict Standards</b>: Non-static method SELanguage::_init() should not be called statically, assuming $this from incompatible context in <b>/home3/nextron/public_html/include/language/language.php</b> on line <b>614</b><br /> insciences
Strict Standards: Non-static method SELanguage::_preload_multi() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/smarty/templates_c/%%87^870^870F1A81%%headerx.tpl.php on line 6

Strict Standards: Non-static method SELanguage::_init() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/language/language.php on line 529

Strict Standards: Non-static method SELanguage::load() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/smarty/templates_c/%%87^870^870F1A81%%headerx.tpl.php on line 7

Strict Standards: Non-static method SELanguage::_init() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/language/language.php on line 686
Keyword Tag Sort by


Categories: Afinitor Cancer Herceptin

Afinitor® shows potential to reverse resistance to Herceptin®[*] in metastatic breast cancer patients, leading to Phase III tria

·        Afinitor (RAD001) combined with Herceptin and chemotherapy in two separate Phase I trials halted tumor growth in 77% and 62% of patients, respectively

 

·        Novartis to start Phase III clinical trial program to explore Afinitor, an oral mTOR inhibitor, as combination treatment with Herceptin and chemotherapy

 

Basel, December 12, 2008 - New data from two early clinical studies show that Afinitor® (everolimus) may overcome resistance to Herceptin® (trastuzumab)[*] in women with HER2- positive metastatic breast cancer[1],[2]. These results support the initiation of a Phase III clinical trial program to fully explore the potential of Afinitor, also known as RAD001, in breast cancer.
 
 
Two Phase I studies were presented today during the CTRC-AACR San Antonio Breast Cancer Symposium. Initial results from both studies were released earlier this year at the American Society of Clinical Oncology (ASCO) annual meeting.
 
 
Updated results from the first Phase I trial show that the combination of Afinitor with Herceptin and weekly Taxol® (paclitaxel)[**] halted tumor growth in 77% of patients with HER2-positive metastatic breast cancer with documented resistance to Herceptin. In addition, the data demonstrated the first complete response in the trial.
 
In addition, updated data from the second Phase I study show promising anticancer activity for Afinitor in combination with Herceptin and Navelbine® (vinorelbine)[***] in heavily pretreated Herceptin-resistant patients with HER2-positive metastatic breast cancer. In the study, Afinitor in combination with Herceptin and Navelbine halted tumor growth in 62% of patients[2].
 
 
"Data presented at this meeting affirm the potential of Afinitor to reverse Herceptin resistance and restore patient response to treatment," said Ruth O'Regan, MD, Emory University School of Medicine, Atlanta, GA. "These findings are important for patients with HER2-positive metastatic breast cancer who develop resistance to Herceptin."
 
Preclinical data have shown that Afinitor, an inhibitor of mTOR, acts on the pathway that mediates Herceptin resistance and has the potential to help restore response in these patients. Afinitor works through direct antitumor activity and through its influence on two of the most important pathways for breast cancer, the erbB receptor and the HER2 pathways.
 
 
"We are encouraged by the benefit Afinitor provided to advanced breast cancer patients in these early trials," said Alessandro Riva, MD, Executive Vice President & Global Head of Development, Novartis Oncology. "Novartis is committed to further evaluating the potential of Afinitor in combination with Herceptin as a new treatment regimen in breast cancer, as well as to studying its role in treating other tumor types."
 
 
Novartis will initiate a worldwide Phase III clinical trial program to further evaluate the potential of Afinitor in combination with Herceptin and chemotherapy in patients with HER2-positive metastatic breast cancer.
 
 
 
Study details: abstract #3119
 
An open-label, multicenter Phase I dose escalation trial evaluated daily Afinitor (5 mg, 10 mg) and weekly Afinitor (30 mg, 50 mg and 70 mg) regimens in combination with Taxol (80 mg/m2 IV over 60 min on days 1, 8 and 15 every 28 days) and Herceptin (2 mg/kg IV over 30 min) in heavily pretreated patients with HER2-positive metastatic breast cancer with prior resistance to Herceptin [1].
 
 
Across treatment arms, there was an overall disease control rate of 77% (complete response/partial response/stable disease >16 weeks). Twenty-two heavily pretreated patients were evaluable for efficacy: treatment arms included five patients assigned to Afinitor 5 mg daily, eight to Afinitor 10 mg daily and nine to Afinitor 30 mg weekly. Among the five patients evaluated in the 5 mg daily treatment arm, one patient had a complete response and four patients had partial responses. In the 10 mg daily treatment arm, one patient had a partial response, six patients had stable disease and one patient had progressive disease. Among the nine patients evaluated in the 30 mg weekly treatment arm, three patients had partial responses, five patients had stable disease and one patient had progressive disease. The critical dose-limiting toxicities occurring in the first cycle of treatment included febrile neutropenia, oral mucositis and confusion, occurring in the 5 mg daily, 10 mg daily and 30 mg weekly treatment groups, respectively[1]. The most commonly reported grade 3/4 adverse events (> 10%) suspected of being related to study treatment were neutropenia, lymphopenia, stomatitis, leukopenia, alopecia and anemia.
 
 
 
Study details: abstract #406
 
An open-label, multicenter, Phase I trial evaluated daily Afinitor (2.5 mg, 5 mg, 10 mg) and weekly Afinitor (20 mg, 30 mg, 50 mg and 70 mg) in combination with Navelbine (25 mg/m2 IV over 10-15 min on days 1 and 8 every 21 days) and Herceptin (2 mg/kg IV over 30 min). All patients entering the study had progression on, or shortly after, treatment with Herceptin and all had received prior taxane. The median number of prior chemotherapy regimens was 3 (range: 1-5)[2].
 
 
Across treatment arms, there was an overall disease control rate of 62% (complete response/partial response/stable disease >16 weeks). Thirty-four heavily pretreated patients were evaluated to date (fifteen patients assigned to Afinitor 5 mg daily, six to Afinitor 20 mg weekly, and thirteen to Afinitor 30 mg weekly). Among the fifteen patients in the 5 mg daily treatment arm, one patient had a complete response, two patients had partial responses, nine patients had stable disease and three patients had progressive disease. Among the six patients in the 20 mg weekly treatment arm, one patient had a partial response, three patients had stable disease and two patients had progressive disease. Among the thirteen patients evaluated in the 30 mg weekly treatment arm, two patients had partial responses, nine patients had stable disease and two patients had progressive disease. The critical dose-limiting toxicities (i.e., dose-limiting toxicities in cycle 1) occurring in the 5 mg daily treatment group included grade 3/4 neutropenia, grade 3 stomatitis, grade 3 fatigue and grade 3 anorexia. In the 30 mg weekly treatment group, grade 3/4 neutropenia was the only critical dose-limiting toxicity. There were no critical dose-limiting toxicities in the 20 mg weekly Afinitor treatment arm. The most commonly reported grade 3/4 adverse events (> 10%) suspected of being related to study treatment was neutropenia, stomatitis and leukopenia[2].
 
 
 
About breast cancer
 
Worldwide, breast cancer is the fifth most common cause of cancer death. Every year breast cancer causes 548,000 deaths worldwide[3]. The incidence of breast cancer is rising among women in many European countries, affecting up to one in 16 women[4].
 
 
Inside a breast there are many lobes, ducts and vessels that support several important functions in the body, including reproductive needs and fighting infection. In breast cancer, some of the cells in the breast begin growing abnormally and divide more rapidly than healthy cells. The quick division of cells may cause spreading through the breast, to the lymph nodes or to other parts of the body.
 
 
 
About Afinitor
 
Afinitor, an oral once-daily inhibitor of mTOR, is an investigational drug being studied in multiple tumor types. In cancer cells, Afinitor provides continuous inhibition of mTOR, a protein that acts as a central regulator of tumor cell division, cell metabolism and blood vessel growth.
 
 
The safety and efficacy profile of Afinitor has not yet been established in oncology and there is no guarantee that Afinitor will become commercially available for oncology indications. The active ingredient in Afinitor is everolimus, which is available in different dosage strengths under the trade name Certican® for the prevention of organ rejection in heart and kidney transplant recipients. Certican was first approved in the EU in 2003.
 
 
In addition to breast cancer, Afinitor is being evaluated as a single agent or in combination with existing therapies in renal cell carcinoma, neuroendocrine tumors, lymphoma, gastric, lung and other cancers, as well as tuberous sclerosis complex.
 
 
 
Disclaimer
 
The foregoing release contains forward-looking statements that can be identified by terminology such as "potential," "to start," "to explore," "may," "to fully explore," "promising," "encouraged," "committed," "will," "to further evaluate," or similar expressions, or by express or implied discussions regarding potential regulatory filings or marketing approvals for Afinitor or regarding potential future revenues from Afinitor. You should not place undue reliance on these statements. Such forward-looking statements reflect the current views of management regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results with Afinitor to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Afinitor will be approved for sale for any oncology indication in any market. Nor can there be any guarantee that Afinitor will achieve any particular levels of revenue in the future. In particular, management's expectations regarding Afinitor a could be affected by, among other things, unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; unexpected regulatory actions or delays or government regulation generally; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; government, industry and general public pricing pressures; the impact that the foregoing factors could have on the values attributed to the Novartis Group's assets and liabilities as recorded in the Group's consolidated balance sheet, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.
 
 
 
About Novartis
 
Novartis AG provides healthcare solutions that address the evolving needs of patients and societies. Focused solely on healthcare, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, cost-saving generic pharmaceuticals, preventive vaccines, diagnostic tools and consumer health products. Novartis is the only company with leading positions in these areas. In 2007, the Group's continuing operations (excluding divestments in 2007) achieved net sales of USD 38.1 billion and net income of USD 6.5 billion. Approximately USD 6.4 billion was invested in R&D activities throughout the Group. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 97,000 full-time associates and operate in over 140 countries around the world. For more information, please visit http://www.novartis.com.
 
 
 
References
 
[1] O'Regan, R., et al. RAD001 (everolimus) in Combinations with Weekly Paclitaxel and Trastuzumab in Patients with HER-2-Overexpressing Metastatic Breast Cancer with Prior Resistance to Trastuzumab: A Multicenter Phase I Clinical Trial. Poster presented at SABCS 2008.
 
[2] Fasolo, A., et al. Multicenter Phase I Clinical Trial of Daily and Weekly Everolimus (RAD001) in Combination with Vinorelbine and Trastuzumab in Patients with HER-2-Overexpressing in Metastatic Breast Cancer with Prior Resistance to Trastuzumab. Poster presented at SABCS 2008.
 
[3] World Health Organization. Media Centre: Cancer Fact Sheet http://www.who.int/mediacentre/factsheets/fs297/en/
 
[4] World Health Organization Regional Office for Europe. Reproductive Health and Research: Breast Cancer
 
 
[*] In the US, Herceptin is a registered trademark of Genentech, Inc. Internationally, Herceptin is a registered trademark of Roche.
 
[**] Taxol is a registered trademark of Bristol-Myers Squibb Company.
 
[***] Navelbine is a registered trademark of Pierre Fabre Pharmaceuticals Inc.
 
 
 
Contact:  Geoff Cook, Novartis Pharma Communications, +1 862 778 2675 (direct), +1 973 652 7927(mobile), geoffrey.cook@novartis.com

Source:  Novartis

Related News:

Protein that accelerates age, brakes cancer 11 August 2013, 12:57
Prelamin A protein causes accelerated ageing disorders and also prevents the spread of cancer...

Study IDs key protein for cell death 16 May 2013, 04:32
Findings may offer a new way to kill cancer cells by forcing them into an alternative...

Mapping of cancer cell fuel pumps paves the way for new drugs 29 April 2013, 03:26
For the first time, researchers at Karolinska Institutet have managed to obtain detailed images...

Understanding Abnormal Proteins in Degenerative Diseases 22 April 2013, 07:55
New IBN Peptides May Help Researchers Combat Alzheimer’s, Diabetes and...

Combination therapy with experimental drug improves outlook for... 5 December 2012, 08:08
A combination therapy using an experimental new drug shows significant promise for women with a...

Novartis highlights key data in patients with hematologic diseases... 28 November 2012, 03:13
Long-term follow-up data from Jakavi® Phase III trials in patients with the debilitating...

A*STAR Scientists Identify Potential Drug Target For Inflammatory... 21 November 2012, 03:24
This discovery holds the potential to reduce healthcare costs for many common inflammatory...

Gene switch important in cancer discovered 2 November 2012, 03:10
Scientists at Karolinska Institutet in Sweden and the University of Helsinki in Finland have...

Obesity Promotes Tumor Growth Regardless of Diet 15 October 2012, 03:37
Presence of fat tissue-derived cells in tumors is related to increased tumor growth. The...

How Cancer Cells Break Free From Tumors 11 October 2012, 04:02
New MIT study identifies adhesion molecules key to cancer’s spread through the body.CAMBRIDGE,...

Sign up for daily newsletter

Subscribe to daily Science News
(a free e-mail delivery powered by Google)

Top Categories



Strict Standards: Non-static method SELanguage::load() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/smarty/templates_c/%%47^479^479B3B2F%%insciences.tpl.php on line 4

Strict Standards: Non-static method SELanguage::_init() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/language/language.php on line 686

image

We have launched our peer- reviewed, Open-access journal: Insciences Journal

Recently added

27.11.12
Consequential Life Cycle Assessment of Nitrogen Fertilisers Based on Biomass – a Swedish perspective

08.11.12
From Molecular Hollows to Imprinting Strategies – Mass-Sensitive Devices in Host-Guest Chemistry

26.04.12
CdSe/ZnSe Quantum-Dot Semiconductor Optical Amplifiers

23.03.12
Screen-printed Electrochemical Sensors and Biosensors for Monitoring Metal Pollutants


 
 

Strict Standards: Non-static method SELanguage::load() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/smarty/templates_c/%%76^762^76224BF7%%footerx.tpl.php on line 6

Strict Standards: Non-static method SELanguage::_init() should not be called statically, assuming $this from incompatible context in /home3/nextron/public_html/include/language/language.php on line 686