Phase I Study of SS1P, a Recombinant Anti-Mesothelin Immunotoxin Given as a Bolus I.V. Infusion to Patients with Mesothelin-Expressing Mesothelioma, Ovarian, and Pancreatic Cancers
Purpose: To determine the toxicities, maximum tolerated dose (MTD) and pharmacokinetics of the recombinant immunotoxin SS1P (anti-mesothelin dsFv-PE38) in patients with mesothelin-expressing cancers. Experimental Design: SS1P given as a 30-min i.v. infusion every other day (QOD) for six or three dos...
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| Veröffentlicht in: | Clinical cancer research 2007-09, Vol.13 (17), p.5144-5149 |
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| creator | HASSAN, Raffit BULLOCK, Susie PREMKUMAR, Ahalya KREITMAN, Robert J KINDLER, Hedy WILLINGHAM, Mark C PASTAN, Ira |
| description | Purpose: To determine the toxicities, maximum tolerated dose (MTD) and pharmacokinetics of the recombinant immunotoxin SS1P (anti-mesothelin
dsFv-PE38) in patients with mesothelin-expressing cancers.
Experimental Design: SS1P given as a 30-min i.v. infusion every other day (QOD) for six or three doses was administered to 34 patients with advanced
mesothelioma ( n = 20), ovarian ( n = 12), and pancreatic ( n = 2) cancer.
Results: The initial cohort of 17 patients received SS1P QOD × 6 doses and the MTD was 18 μg/kg/dose. Dose-limiting toxicities (DLT)
included grade 3 uticaria (one patient) and grade 3 vascular leak syndrome (two patients). To allow further SS1P dose escalation,
17 patients were treated on the QOD × 3 schedule and the MTD was 45 μg/kg/dose. The DLT was grade 3 pleuritis and was seen
in two of two patients treated at a dose of 60 μg/kg and in one of nine patients treated at a dose of 45 μg/kg. At the MTD
of 45 μg/kg, the mean C max of SS1P was 483 ng/mL and half-life was 466 min. Of the 33 evaluable patients treated, 4 had minor responses, 19 had stable
disease (including 2 with resolution of ascites), and 10 had progressive disease.
Conclusions: SS1P is well tolerated with pleuritis as the DLT at the highest dose level. Evidence of clinical activity was noted in a
group of heavily pretreated patients. Phase II clinical trials of SS1P are being planned for malignant mesothelioma and other
mesothelin-expressing malignancies. |
| doi_str_mv | 10.1158/1078-0432.CCR-07-0869 |
| format | Article |
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dsFv-PE38) in patients with mesothelin-expressing cancers.
Experimental Design: SS1P given as a 30-min i.v. infusion every other day (QOD) for six or three doses was administered to 34 patients with advanced
mesothelioma ( n = 20), ovarian ( n = 12), and pancreatic ( n = 2) cancer.
Results: The initial cohort of 17 patients received SS1P QOD × 6 doses and the MTD was 18 μg/kg/dose. Dose-limiting toxicities (DLT)
included grade 3 uticaria (one patient) and grade 3 vascular leak syndrome (two patients). To allow further SS1P dose escalation,
17 patients were treated on the QOD × 3 schedule and the MTD was 45 μg/kg/dose. The DLT was grade 3 pleuritis and was seen
in two of two patients treated at a dose of 60 μg/kg and in one of nine patients treated at a dose of 45 μg/kg. At the MTD
of 45 μg/kg, the mean C max of SS1P was 483 ng/mL and half-life was 466 min. Of the 33 evaluable patients treated, 4 had minor responses, 19 had stable
disease (including 2 with resolution of ascites), and 10 had progressive disease.
Conclusions: SS1P is well tolerated with pleuritis as the DLT at the highest dose level. Evidence of clinical activity was noted in a
group of heavily pretreated patients. Phase II clinical trials of SS1P are being planned for malignant mesothelioma and other
mesothelin-expressing malignancies.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-07-0869</identifier><identifier>PMID: 17785569</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Adult ; Aged ; Antibodies, Monoclonal - administration & dosage ; Antibodies, Monoclonal - adverse effects ; Antibodies, Monoclonal - pharmacokinetics ; antibody therapy ; Antineoplastic agents ; Biological and medical sciences ; clinical trial ; Female ; Female genital diseases ; Gastroenterology. Liver. Pancreas. Abdomen ; Gynecology. Andrology. Obstetrics ; Humans ; immunotherapy ; Immunotoxins - administration & dosage ; Injections, Intravenous ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Male ; Medical sciences ; Mesothelioma - drug therapy ; Middle Aged ; Ovarian Neoplasms - drug therapy ; Pancreatic Neoplasms - drug therapy ; peritoneal mesothelioma ; Pharmacology. Drug treatments ; Targeted therapy ; Tumors</subject><ispartof>Clinical cancer research, 2007-09, Vol.13 (17), p.5144-5149</ispartof><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c449t-1680dbadcf5e23af18b832edcb9bf2f4e22e89bbb6a029363e06cbabc8bc2323</citedby><cites>FETCH-LOGICAL-c449t-1680dbadcf5e23af18b832edcb9bf2f4e22e89bbb6a029363e06cbabc8bc2323</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3356,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19084461$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17785569$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>HASSAN, Raffit</creatorcontrib><creatorcontrib>BULLOCK, Susie</creatorcontrib><creatorcontrib>PREMKUMAR, Ahalya</creatorcontrib><creatorcontrib>KREITMAN, Robert J</creatorcontrib><creatorcontrib>KINDLER, Hedy</creatorcontrib><creatorcontrib>WILLINGHAM, Mark C</creatorcontrib><creatorcontrib>PASTAN, Ira</creatorcontrib><title>Phase I Study of SS1P, a Recombinant Anti-Mesothelin Immunotoxin Given as a Bolus I.V. Infusion to Patients with Mesothelin-Expressing Mesothelioma, Ovarian, and Pancreatic Cancers</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Purpose: To determine the toxicities, maximum tolerated dose (MTD) and pharmacokinetics of the recombinant immunotoxin SS1P (anti-mesothelin
dsFv-PE38) in patients with mesothelin-expressing cancers.
Experimental Design: SS1P given as a 30-min i.v. infusion every other day (QOD) for six or three doses was administered to 34 patients with advanced
mesothelioma ( n = 20), ovarian ( n = 12), and pancreatic ( n = 2) cancer.
Results: The initial cohort of 17 patients received SS1P QOD × 6 doses and the MTD was 18 μg/kg/dose. Dose-limiting toxicities (DLT)
included grade 3 uticaria (one patient) and grade 3 vascular leak syndrome (two patients). To allow further SS1P dose escalation,
17 patients were treated on the QOD × 3 schedule and the MTD was 45 μg/kg/dose. The DLT was grade 3 pleuritis and was seen
in two of two patients treated at a dose of 60 μg/kg and in one of nine patients treated at a dose of 45 μg/kg. At the MTD
of 45 μg/kg, the mean C max of SS1P was 483 ng/mL and half-life was 466 min. Of the 33 evaluable patients treated, 4 had minor responses, 19 had stable
disease (including 2 with resolution of ascites), and 10 had progressive disease.
Conclusions: SS1P is well tolerated with pleuritis as the DLT at the highest dose level. Evidence of clinical activity was noted in a
group of heavily pretreated patients. Phase II clinical trials of SS1P are being planned for malignant mesothelioma and other
mesothelin-expressing malignancies.</description><subject>Adult</subject><subject>Aged</subject><subject>Antibodies, Monoclonal - administration & dosage</subject><subject>Antibodies, Monoclonal - adverse effects</subject><subject>Antibodies, Monoclonal - pharmacokinetics</subject><subject>antibody therapy</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>clinical trial</subject><subject>Female</subject><subject>Female genital diseases</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>immunotherapy</subject><subject>Immunotoxins - administration & dosage</subject><subject>Injections, Intravenous</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mesothelioma - drug therapy</subject><subject>Middle Aged</subject><subject>Ovarian Neoplasms - drug therapy</subject><subject>Pancreatic Neoplasms - drug therapy</subject><subject>peritoneal mesothelioma</subject><subject>Pharmacology. Drug treatments</subject><subject>Targeted therapy</subject><subject>Tumors</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkdtu1DAURSMEoqXwCSC_gITUDL7l9lhGbYlU1FGn4tWynZPGKLGnttPLf_UD8XQGzZO3rLW3j8_Oss8ELwgp6h8EV3WOOaOL5fImx1WO67J5kx2ToqhyRsvibdL_maPsQwh_MSacYP4-OyJVVRdF2RxnL6tBBkAtWse5e0auR-s1WZ0iiW5Au0kZK21EZzaa_DcEFwcYjUXtNM3WRfeU9KV5AItkSJafbpwDahd_Fqi1_RyMsyg6tJLRgI0BPZo4oENMfv608RCCsXeHWzfJU3T9IL2RNo1hu2S32kPK0GiZJPjwMXvXyzHAp_15kt1enN8uf-VX15ft8uwq15w3MSdljTslO90XQJnsSa1qRqHTqlE97TlQCnWjlColpg0rGeBSK6l0rTRllJ1k33axG-_uZwhRTCZoGEdpwc1BkKZiTVGSBBY7UHsXgodebLyZpH8WBIttW2LbhNg2IVJbAldi21byfdk_MKsJuoNrX08Cvu4BGbQce5_-b8KBa3DN-esA33fcYO6GR-NB6NdNpe2C9HoQhKVQURDO2T8GJ658</recordid><startdate>20070901</startdate><enddate>20070901</enddate><creator>HASSAN, Raffit</creator><creator>BULLOCK, Susie</creator><creator>PREMKUMAR, Ahalya</creator><creator>KREITMAN, Robert J</creator><creator>KINDLER, Hedy</creator><creator>WILLINGHAM, Mark C</creator><creator>PASTAN, Ira</creator><general>American Association for Cancer Research</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>7QO</scope><scope>7T5</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope></search><sort><creationdate>20070901</creationdate><title>Phase I Study of SS1P, a Recombinant Anti-Mesothelin Immunotoxin Given as a Bolus I.V. Infusion to Patients with Mesothelin-Expressing Mesothelioma, Ovarian, and Pancreatic Cancers</title><author>HASSAN, Raffit ; BULLOCK, Susie ; PREMKUMAR, Ahalya ; KREITMAN, Robert J ; KINDLER, Hedy ; WILLINGHAM, Mark C ; PASTAN, Ira</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c449t-1680dbadcf5e23af18b832edcb9bf2f4e22e89bbb6a029363e06cbabc8bc2323</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antibodies, Monoclonal - administration & dosage</topic><topic>Antibodies, Monoclonal - adverse effects</topic><topic>Antibodies, Monoclonal - pharmacokinetics</topic><topic>antibody therapy</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>clinical trial</topic><topic>Female</topic><topic>Female genital diseases</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>immunotherapy</topic><topic>Immunotoxins - administration & dosage</topic><topic>Injections, Intravenous</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mesothelioma - drug therapy</topic><topic>Middle Aged</topic><topic>Ovarian Neoplasms - drug therapy</topic><topic>Pancreatic Neoplasms - drug therapy</topic><topic>peritoneal mesothelioma</topic><topic>Pharmacology. Drug treatments</topic><topic>Targeted therapy</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>HASSAN, Raffit</creatorcontrib><creatorcontrib>BULLOCK, Susie</creatorcontrib><creatorcontrib>PREMKUMAR, Ahalya</creatorcontrib><creatorcontrib>KREITMAN, Robert J</creatorcontrib><creatorcontrib>KINDLER, Hedy</creatorcontrib><creatorcontrib>WILLINGHAM, Mark C</creatorcontrib><creatorcontrib>PASTAN, Ira</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>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>HASSAN, Raffit</au><au>BULLOCK, Susie</au><au>PREMKUMAR, Ahalya</au><au>KREITMAN, Robert J</au><au>KINDLER, Hedy</au><au>WILLINGHAM, Mark C</au><au>PASTAN, Ira</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phase I Study of SS1P, a Recombinant Anti-Mesothelin Immunotoxin Given as a Bolus I.V. Infusion to Patients with Mesothelin-Expressing Mesothelioma, Ovarian, and Pancreatic Cancers</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2007-09-01</date><risdate>2007</risdate><volume>13</volume><issue>17</issue><spage>5144</spage><epage>5149</epage><pages>5144-5149</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Purpose: To determine the toxicities, maximum tolerated dose (MTD) and pharmacokinetics of the recombinant immunotoxin SS1P (anti-mesothelin
dsFv-PE38) in patients with mesothelin-expressing cancers.
Experimental Design: SS1P given as a 30-min i.v. infusion every other day (QOD) for six or three doses was administered to 34 patients with advanced
mesothelioma ( n = 20), ovarian ( n = 12), and pancreatic ( n = 2) cancer.
Results: The initial cohort of 17 patients received SS1P QOD × 6 doses and the MTD was 18 μg/kg/dose. Dose-limiting toxicities (DLT)
included grade 3 uticaria (one patient) and grade 3 vascular leak syndrome (two patients). To allow further SS1P dose escalation,
17 patients were treated on the QOD × 3 schedule and the MTD was 45 μg/kg/dose. The DLT was grade 3 pleuritis and was seen
in two of two patients treated at a dose of 60 μg/kg and in one of nine patients treated at a dose of 45 μg/kg. At the MTD
of 45 μg/kg, the mean C max of SS1P was 483 ng/mL and half-life was 466 min. Of the 33 evaluable patients treated, 4 had minor responses, 19 had stable
disease (including 2 with resolution of ascites), and 10 had progressive disease.
Conclusions: SS1P is well tolerated with pleuritis as the DLT at the highest dose level. Evidence of clinical activity was noted in a
group of heavily pretreated patients. Phase II clinical trials of SS1P are being planned for malignant mesothelioma and other
mesothelin-expressing malignancies.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>17785569</pmid><doi>10.1158/1078-0432.CCR-07-0869</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Clinical cancer research, 2007-09, Vol.13 (17), p.5144-5149 |
| issn | 1078-0432 1557-3265 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; American Association for Cancer Research; Alma/SFX Local Collection |
| subjects | Adult Aged Antibodies, Monoclonal - administration & dosage Antibodies, Monoclonal - adverse effects Antibodies, Monoclonal - pharmacokinetics antibody therapy Antineoplastic agents Biological and medical sciences clinical trial Female Female genital diseases Gastroenterology. Liver. Pancreas. Abdomen Gynecology. Andrology. Obstetrics Humans immunotherapy Immunotoxins - administration & dosage Injections, Intravenous Liver. Biliary tract. Portal circulation. Exocrine pancreas Male Medical sciences Mesothelioma - drug therapy Middle Aged Ovarian Neoplasms - drug therapy Pancreatic Neoplasms - drug therapy peritoneal mesothelioma Pharmacology. Drug treatments Targeted therapy Tumors |
| title | Phase I Study of SS1P, a Recombinant Anti-Mesothelin Immunotoxin Given as a Bolus I.V. Infusion to Patients with Mesothelin-Expressing Mesothelioma, Ovarian, and Pancreatic Cancers |
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