Phase I study of TCNU, a novel nitrosourea
TCNU is a chloroethyl nitrosourea based on the endogenous amino acid taurine. This paper reports its first evaluation in man. Eighty-four patients with refractory cancer received 12 dose escalations from 10–150 mg/m 2 TCNU administered orally every 6 weeks. Clinical side-effects were predominantly g...
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| Veröffentlicht in: | European journal of cancer & clinical oncology 1987-12, Vol.23 (12), p.1845-1849 |
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| container_issue | 12 |
| container_start_page | 1845 |
| container_title | European journal of cancer & clinical oncology |
| container_volume | 23 |
| creator | Smyth, J.F. MacPherson, J.S. Warrington, P.S. Kerr, M.E. Whelan, J.M. Cornbleet, M.A. Leonard, R.C.F. |
| description | TCNU is a chloroethyl nitrosourea based on the endogenous amino acid taurine. This paper reports its first evaluation in man. Eighty-four patients with refractory cancer received
12 dose escalations from
10–150 mg/m
2
TCNU administered orally every
6 weeks. Clinical side-effects were predominantly gastro-intestinal but dose-limiting toxicity was thrombocytopenia. Pharmacokinetic monitoring with an HPLC assay sensitive to the nanogram range demonstrated unchanged TCNU in plasma for up to
8 h following administration. The mean half-life was
60 min. Clinical responses were seen in melanoma (four patients), lung cancer (two squamous, one small cell) and one patient each with renal and stomach cancer. These responses, together with the unusual pharmacokinetic profile of TCNU, warrant exploration in disease-orientated phase II studies at a recommended dose of
130 mg/m
2
p.o. q
5 weeeks. |
| doi_str_mv | 10.1016/0277-5379(87)90050-2 |
| format | Article |
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12 dose escalations from
10–150 mg/m
2
TCNU administered orally every
6 weeks. Clinical side-effects were predominantly gastro-intestinal but dose-limiting toxicity was thrombocytopenia. Pharmacokinetic monitoring with an HPLC assay sensitive to the nanogram range demonstrated unchanged TCNU in plasma for up to
8 h following administration. The mean half-life was
60 min. Clinical responses were seen in melanoma (four patients), lung cancer (two squamous, one small cell) and one patient each with renal and stomach cancer. These responses, together with the unusual pharmacokinetic profile of TCNU, warrant exploration in disease-orientated phase II studies at a recommended dose of
130 mg/m
2
p.o. q
5 weeeks.</description><identifier>ISSN: 0277-5379</identifier><identifier>DOI: 10.1016/0277-5379(87)90050-2</identifier><identifier>PMID: 3436348</identifier><identifier>CODEN: EJCODS</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Adolescent ; Adult ; Aged ; Antineoplastic agents ; Antineoplastic Agents - adverse effects ; Antineoplastic Agents - pharmacokinetics ; Antineoplastic Agents - therapeutic use ; Applied sciences ; Biological and medical sciences ; Chemotherapy ; Dose-Response Relationship, Drug ; Drug Evaluation ; Exact sciences and technology ; Female ; Hematologic Diseases - chemically induced ; Humans ; Male ; Medical sciences ; Middle Aged ; Nausea - chemically induced ; Neoplasms - drug therapy ; Neoplasms - metabolism ; Nitrosourea Compounds - adverse effects ; Nitrosourea Compounds - pharmacokinetics ; Nitrosourea Compounds - therapeutic use ; Other techniques and industries ; Pharmacology. Drug treatments ; Taurine - adverse effects ; Taurine - analogs & derivatives ; Taurine - pharmacokinetics ; Taurine - therapeutic use ; Vomiting - chemically induced</subject><ispartof>European journal of cancer & clinical oncology, 1987-12, Vol.23 (12), p.1845-1849</ispartof><rights>1987</rights><rights>1989 INIST-CNRS</rights><rights>1988 INIST-CNRS</rights><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c446t-2d5673ef0385a788f59ff0c00c796584db3bce65fa2924ff1afcd773c32a47843</citedby><cites>FETCH-LOGICAL-c446t-2d5673ef0385a788f59ff0c00c796584db3bce65fa2924ff1afcd773c32a47843</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=7074176$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=7484358$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/3436348$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Smyth, J.F.</creatorcontrib><creatorcontrib>MacPherson, J.S.</creatorcontrib><creatorcontrib>Warrington, P.S.</creatorcontrib><creatorcontrib>Kerr, M.E.</creatorcontrib><creatorcontrib>Whelan, J.M.</creatorcontrib><creatorcontrib>Cornbleet, M.A.</creatorcontrib><creatorcontrib>Leonard, R.C.F.</creatorcontrib><title>Phase I study of TCNU, a novel nitrosourea</title><title>European journal of cancer & clinical oncology</title><addtitle>Eur J Cancer Clin Oncol</addtitle><description>TCNU is a chloroethyl nitrosourea based on the endogenous amino acid taurine. This paper reports its first evaluation in man. Eighty-four patients with refractory cancer received
12 dose escalations from
10–150 mg/m
2
TCNU administered orally every
6 weeks. Clinical side-effects were predominantly gastro-intestinal but dose-limiting toxicity was thrombocytopenia. Pharmacokinetic monitoring with an HPLC assay sensitive to the nanogram range demonstrated unchanged TCNU in plasma for up to
8 h following administration. The mean half-life was
60 min. Clinical responses were seen in melanoma (four patients), lung cancer (two squamous, one small cell) and one patient each with renal and stomach cancer. These responses, together with the unusual pharmacokinetic profile of TCNU, warrant exploration in disease-orientated phase II studies at a recommended dose of
130 mg/m
2
p.o. q
5 weeeks.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Antineoplastic agents</subject><subject>Antineoplastic Agents - adverse effects</subject><subject>Antineoplastic Agents - pharmacokinetics</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Applied sciences</subject><subject>Biological and medical sciences</subject><subject>Chemotherapy</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Evaluation</subject><subject>Exact sciences and technology</subject><subject>Female</subject><subject>Hematologic Diseases - chemically induced</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Nausea - chemically induced</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - metabolism</subject><subject>Nitrosourea Compounds - adverse effects</subject><subject>Nitrosourea Compounds - pharmacokinetics</subject><subject>Nitrosourea Compounds - therapeutic use</subject><subject>Other techniques and industries</subject><subject>Pharmacology. Drug treatments</subject><subject>Taurine - adverse effects</subject><subject>Taurine - analogs & derivatives</subject><subject>Taurine - pharmacokinetics</subject><subject>Taurine - therapeutic use</subject><subject>Vomiting - chemically induced</subject><issn>0277-5379</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1987</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEtLw0AUhWeh1Fr9BwpZiKgYncw7G0GKj0JRF-16mE7u4Eia1Jmk0H9vakOXurpwz3cP5x6EzjJ8l-FM3GMiZcqpzK-UvM4x5jglB2i4Xx-h4xi_MCaKcTpAA8qooEwN0c3Hp4mQTJLYtMUmqV0yG7_NbxOTVPUayqTyTahj3QYwJ-jQmTLCaT9HaP78NBu_ptP3l8n4cZpaxkSTkoILScFhqriRSjmeO4ctxlbmgitWLOjCguDOkJww5zLjbCEltZQYJhWjI3S5812F-ruF2OiljxbK0lRQt1FnHDOhctyBbAfaLmIM4PQq-KUJG51hva1Fb__X2_-1kvq3Fk26s_Pev10sodgf9Z10-kWvm2hN6YKprI97TLIuI_8fw5JlUnTYww6DrrK1h6Cj9VBZKHwA2-ii9n_H_QGMdYov</recordid><startdate>19871201</startdate><enddate>19871201</enddate><creator>Smyth, J.F.</creator><creator>MacPherson, J.S.</creator><creator>Warrington, P.S.</creator><creator>Kerr, M.E.</creator><creator>Whelan, J.M.</creator><creator>Cornbleet, M.A.</creator><creator>Leonard, R.C.F.</creator><general>Elsevier Ltd</general><general>Pergamon Press</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>19871201</creationdate><title>Phase I study of TCNU, a novel nitrosourea</title><author>Smyth, J.F. ; MacPherson, J.S. ; Warrington, P.S. ; Kerr, M.E. ; Whelan, J.M. ; Cornbleet, M.A. ; Leonard, R.C.F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c446t-2d5673ef0385a788f59ff0c00c796584db3bce65fa2924ff1afcd773c32a47843</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1987</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Antineoplastic agents</topic><topic>Antineoplastic Agents - adverse effects</topic><topic>Antineoplastic Agents - pharmacokinetics</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Applied sciences</topic><topic>Biological and medical sciences</topic><topic>Chemotherapy</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Evaluation</topic><topic>Exact sciences and technology</topic><topic>Female</topic><topic>Hematologic Diseases - chemically induced</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Nausea - chemically induced</topic><topic>Neoplasms - drug therapy</topic><topic>Neoplasms - metabolism</topic><topic>Nitrosourea Compounds - adverse effects</topic><topic>Nitrosourea Compounds - pharmacokinetics</topic><topic>Nitrosourea Compounds - therapeutic use</topic><topic>Other techniques and industries</topic><topic>Pharmacology. Drug treatments</topic><topic>Taurine - adverse effects</topic><topic>Taurine - analogs & derivatives</topic><topic>Taurine - pharmacokinetics</topic><topic>Taurine - therapeutic use</topic><topic>Vomiting - chemically induced</topic><toplevel>online_resources</toplevel><creatorcontrib>Smyth, J.F.</creatorcontrib><creatorcontrib>MacPherson, J.S.</creatorcontrib><creatorcontrib>Warrington, P.S.</creatorcontrib><creatorcontrib>Kerr, M.E.</creatorcontrib><creatorcontrib>Whelan, J.M.</creatorcontrib><creatorcontrib>Cornbleet, M.A.</creatorcontrib><creatorcontrib>Leonard, R.C.F.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>European journal of cancer & clinical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Smyth, J.F.</au><au>MacPherson, J.S.</au><au>Warrington, P.S.</au><au>Kerr, M.E.</au><au>Whelan, J.M.</au><au>Cornbleet, M.A.</au><au>Leonard, R.C.F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phase I study of TCNU, a novel nitrosourea</atitle><jtitle>European journal of cancer & clinical oncology</jtitle><addtitle>Eur J Cancer Clin Oncol</addtitle><date>1987-12-01</date><risdate>1987</risdate><volume>23</volume><issue>12</issue><spage>1845</spage><epage>1849</epage><pages>1845-1849</pages><issn>0277-5379</issn><coden>EJCODS</coden><abstract>TCNU is a chloroethyl nitrosourea based on the endogenous amino acid taurine. This paper reports its first evaluation in man. Eighty-four patients with refractory cancer received
12 dose escalations from
10–150 mg/m
2
TCNU administered orally every
6 weeks. Clinical side-effects were predominantly gastro-intestinal but dose-limiting toxicity was thrombocytopenia. Pharmacokinetic monitoring with an HPLC assay sensitive to the nanogram range demonstrated unchanged TCNU in plasma for up to
8 h following administration. The mean half-life was
60 min. Clinical responses were seen in melanoma (four patients), lung cancer (two squamous, one small cell) and one patient each with renal and stomach cancer. These responses, together with the unusual pharmacokinetic profile of TCNU, warrant exploration in disease-orientated phase II studies at a recommended dose of
130 mg/m
2
p.o. q
5 weeeks.</abstract><cop>Oxford</cop><cop>New York, NY</cop><pub>Elsevier Ltd</pub><pmid>3436348</pmid><doi>10.1016/0277-5379(87)90050-2</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0277-5379 |
| ispartof | European journal of cancer & clinical oncology, 1987-12, Vol.23 (12), p.1845-1849 |
| issn | 0277-5379 |
| language | eng |
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| source | MEDLINE; Alma/SFX Local Collection |
| subjects | Adolescent Adult Aged Antineoplastic agents Antineoplastic Agents - adverse effects Antineoplastic Agents - pharmacokinetics Antineoplastic Agents - therapeutic use Applied sciences Biological and medical sciences Chemotherapy Dose-Response Relationship, Drug Drug Evaluation Exact sciences and technology Female Hematologic Diseases - chemically induced Humans Male Medical sciences Middle Aged Nausea - chemically induced Neoplasms - drug therapy Neoplasms - metabolism Nitrosourea Compounds - adverse effects Nitrosourea Compounds - pharmacokinetics Nitrosourea Compounds - therapeutic use Other techniques and industries Pharmacology. Drug treatments Taurine - adverse effects Taurine - analogs & derivatives Taurine - pharmacokinetics Taurine - therapeutic use Vomiting - chemically induced |
| title | Phase I study of TCNU, a novel nitrosourea |
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