We are analyzing https://link.springer.com/article/10.1007/s00280-010-1506-7.

Title:
Phase I study of LY2181308, an antisense oligonucleotide against survivin, in patients with advanced solid tumors | Cancer Chemotherapy and Pharmacology
Description:
LY2181308 is an antisense oligonucleotide that complementarily binds to survivin mRNA and inhibits its expression in tumor tissue. This phase I dose escalation study evaluated the tolerability, pharmacokinetics, and anticancer activity of LY2181308 in Japanese. Patients with solid tumors refractory to standard therapy received LY2181308 (400, 600, or 750 mg) as a 3-h intravenous infusion for 3 consecutive days and thereafter once a week. LY2181308 was administered to 14 patients, aged 44–73 (median 60) years. Flu-like syndrome, prolonged prothrombin time-international normalized ratio (PT-INR), thrombocytopenia, and fatigue were common reversible grade 1/2 toxicities. The dose-limiting toxicity was reversible grade 3 elevation of ALT/AST/γ-GTP in 1 patient treated at the 750-mg dose. Pharmacokinetic analysis showed a long terminal half-life of 21 days and an extensive tissue distribution of LY2181308. In 12 evaluable patients, one patient had stable disease, while the remaining 11 patients had progressive disease. LY2181308 monotherapy is well tolerated up to 750 mg with a manageable toxicity, the pharmacokinetic profile warrants further evaluation of LY2181308 in combination with cytotoxic agents or radiotherapy.
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Keywords {🔍}

article, cancer, google, scholar, pubmed, survivin, cas, patients, antisense, study, oligonucleotide, phase, solid, yamada, tumors, cells, eli, lilly, japan, privacy, cookies, content, publish, tanioka, nokihara, yamamoto, tamura, expression, therapy, access, cell, search, advanced, goto, sekiguchi, uenaka, callies, pharmacokinetics, gene, data, information, log, journal, research, chemotherapy, november, fujimoto, tissue, dose, japanese,

Topics {✒️}

month download article/chapter article cancer chemotherapy anti-cancer therapy alt/ast/γ-gtp pleiotropic cell-division defects long terminal half-life eortc-nci-aacr symposium cancer therapeutics conference antisense therapeutics antisense oligonucleotide designed modified antisense oligonucleotide full article pdf advanced solid tumors advanced solid malignancies privacy choices/manage cookies solid tumors refractory refractory solid tumors breast cancer cells regulatory subunit alpha anti-apoptosis gene mixed-backbone oligonucleotide antisense oligonucleotide related subjects full-time employees full-time employee myeloid leukemic cells biliary tract cancer human ovarian cancer common terminology criteria european economic area mitotic regulatory proteins de bono js henry sp murine xenograft models sannomiya plaza bldg erl wood manor dose-limiting toxicity survivin expression suppresses altieri dc tnf gene polymorphisms cancer therapeutic target conditions privacy policy continuous infusion schedule eli lilly japan extensive tissue distribution pharmacokinetic profile warrants phosphorothioate oligonucleotide accepting optional cookies scope submit manuscript predicting drug response

Schema {🗺️}

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         headline:Phase I study of LY2181308, an antisense oligonucleotide against survivin, in patients with advanced solid tumors
         description:LY2181308 is an antisense oligonucleotide that complementarily binds to survivin mRNA and inhibits its expression in tumor tissue. This phase I dose escalation study evaluated the tolerability, pharmacokinetics, and anticancer activity of LY2181308 in Japanese. Patients with solid tumors refractory to standard therapy received LY2181308 (400, 600, or 750 mg) as a 3-h intravenous infusion for 3 consecutive days and thereafter once a week. LY2181308 was administered to 14 patients, aged 44–73 (median 60) years. Flu-like syndrome, prolonged prothrombin time-international normalized ratio (PT-INR), thrombocytopenia, and fatigue were common reversible grade 1/2 toxicities. The dose-limiting toxicity was reversible grade 3 elevation of ALT/AST/γ-GTP in 1 patient treated at the 750-mg dose. Pharmacokinetic analysis showed a long terminal half-life of 21 days and an extensive tissue distribution of LY2181308. In 12 evaluable patients, one patient had stable disease, while the remaining 11 patients had progressive disease. LY2181308 monotherapy is well tolerated up to 750 mg with a manageable toxicity, the pharmacokinetic profile warrants further evaluation of LY2181308 in combination with cytotoxic agents or radiotherapy.
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         dateModified:2010-11-16T00:00:00Z
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            Antisense oligonucleotide
            Pharmacokinetics
            Phase I
            Survivin
            Oncology
            Pharmacology/Toxicology
            Cancer Research
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      headline:Phase I study of LY2181308, an antisense oligonucleotide against survivin, in patients with advanced solid tumors
      description:LY2181308 is an antisense oligonucleotide that complementarily binds to survivin mRNA and inhibits its expression in tumor tissue. This phase I dose escalation study evaluated the tolerability, pharmacokinetics, and anticancer activity of LY2181308 in Japanese. Patients with solid tumors refractory to standard therapy received LY2181308 (400, 600, or 750 mg) as a 3-h intravenous infusion for 3 consecutive days and thereafter once a week. LY2181308 was administered to 14 patients, aged 44–73 (median 60) years. Flu-like syndrome, prolonged prothrombin time-international normalized ratio (PT-INR), thrombocytopenia, and fatigue were common reversible grade 1/2 toxicities. The dose-limiting toxicity was reversible grade 3 elevation of ALT/AST/γ-GTP in 1 patient treated at the 750-mg dose. Pharmacokinetic analysis showed a long terminal half-life of 21 days and an extensive tissue distribution of LY2181308. In 12 evaluable patients, one patient had stable disease, while the remaining 11 patients had progressive disease. LY2181308 monotherapy is well tolerated up to 750 mg with a manageable toxicity, the pharmacokinetic profile warrants further evaluation of LY2181308 in combination with cytotoxic agents or radiotherapy.
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      dateModified:2010-11-16T00:00:00Z
      pageStart:505
      pageEnd:511
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         Antisense oligonucleotide
         Pharmacokinetics
         Phase I
         Survivin
         Oncology
         Pharmacology/Toxicology
         Cancer Research
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