Phase I clinical study of the recombinant oncotoxin TP40 in superficial bladder cancer
Transforming growth factor alpha-Pseudomonas exotoxin-40 (TP40) is a hybrid fusion protein that selectively binds to cancer cells that express the epidermal growth factor receptor. TP40 is then internalized and kills these cells by virtue of its Pseudomonas exotoxin-derived domains. We studied the s...
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| Veröffentlicht in: | Clinical cancer research 1995-01, Vol.1 (1), p.57-61 |
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| creator | GOLDBERG, M. R HEIMBROOK, D. C CRAWFORD, E. D OLIFF, A. I PASTAN, I. H RUSSO, P SAROSDY, M. F GREENBERG, R. E GIANTONIO, B. J LINEHAN, W. M WALTHER, M FISHER, H. A. G MESSING, E |
| description | Transforming growth factor alpha-Pseudomonas exotoxin-40 (TP40) is a hybrid fusion protein that selectively binds to cancer
cells that express the epidermal growth factor receptor. TP40 is then internalized and kills these cells by virtue of its
Pseudomonas exotoxin-derived domains. We studied the safety and short-term antitumor activity of intravesical TP40 in 43 patients
with refractory superficial bladder cancer. These patients had resected Ta/T1 disease (n = 19), visible Ta or T1 lesions (n
= 11), or carcinoma in situ (n = 13). Patients were treated with increasing dose levels of TP40 at 0.15, 0.3, 0.6, 1.2, 2.4,
4.8, or 9.6 mg/week for 6 weeks and evaluated by comparing pretreatment and posttreatment cystoscopic examinations, cytology,
and histopathology. All TP40 doses were well tolerated. No evidence of antitumor activity was seen in any of the patients
with Ta or T1 lesions. However, 8 of 9 patients with evaluable carcinoma in situ were judged by histopathology of multiple
biopsy specimens to exhibit clinical improvement following TP40 therapy. In most of these responsive patients, cystoscopic
examination supported the histopathological findings, although cytology of urine and bladder washings persistently demonstrated
malignant cells. Therefore, TP40 appears to be a well-tolerated biological agent that may prove to have utility in treating
carcinoma in situ of the bladder. |
| format | Article |
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cells that express the epidermal growth factor receptor. TP40 is then internalized and kills these cells by virtue of its
Pseudomonas exotoxin-derived domains. We studied the safety and short-term antitumor activity of intravesical TP40 in 43 patients
with refractory superficial bladder cancer. These patients had resected Ta/T1 disease (n = 19), visible Ta or T1 lesions (n
= 11), or carcinoma in situ (n = 13). Patients were treated with increasing dose levels of TP40 at 0.15, 0.3, 0.6, 1.2, 2.4,
4.8, or 9.6 mg/week for 6 weeks and evaluated by comparing pretreatment and posttreatment cystoscopic examinations, cytology,
and histopathology. All TP40 doses were well tolerated. No evidence of antitumor activity was seen in any of the patients
with Ta or T1 lesions. However, 8 of 9 patients with evaluable carcinoma in situ were judged by histopathology of multiple
biopsy specimens to exhibit clinical improvement following TP40 therapy. In most of these responsive patients, cystoscopic
examination supported the histopathological findings, although cytology of urine and bladder washings persistently demonstrated
malignant cells. Therefore, TP40 appears to be a well-tolerated biological agent that may prove to have utility in treating
carcinoma in situ of the bladder.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>PMID: 9815887</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Aged ; Antineoplastic agents ; Antineoplastic Agents - adverse effects ; Biological and medical sciences ; Carcinoma in Situ - drug therapy ; Carcinoma in Situ - pathology ; Dose-Response Relationship, Drug ; Exotoxins - adverse effects ; Female ; Humans ; Immunotherapy ; Male ; Medical sciences ; Middle Aged ; Neoplasm Staging ; Pharmacology. Drug treatments ; Transforming Growth Factor alpha - adverse effects ; Urinary Bladder Neoplasms - drug therapy ; Urinary Bladder Neoplasms - pathology</subject><ispartof>Clinical cancer research, 1995-01, Vol.1 (1), p.57-61</ispartof><rights>1995 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,4010</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3609363$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9815887$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>GOLDBERG, M. R</creatorcontrib><creatorcontrib>HEIMBROOK, D. C</creatorcontrib><creatorcontrib>CRAWFORD, E. D</creatorcontrib><creatorcontrib>OLIFF, A. I</creatorcontrib><creatorcontrib>PASTAN, I. H</creatorcontrib><creatorcontrib>RUSSO, P</creatorcontrib><creatorcontrib>SAROSDY, M. F</creatorcontrib><creatorcontrib>GREENBERG, R. E</creatorcontrib><creatorcontrib>GIANTONIO, B. J</creatorcontrib><creatorcontrib>LINEHAN, W. M</creatorcontrib><creatorcontrib>WALTHER, M</creatorcontrib><creatorcontrib>FISHER, H. A. G</creatorcontrib><creatorcontrib>MESSING, E</creatorcontrib><title>Phase I clinical study of the recombinant oncotoxin TP40 in superficial bladder cancer</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Transforming growth factor alpha-Pseudomonas exotoxin-40 (TP40) is a hybrid fusion protein that selectively binds to cancer
cells that express the epidermal growth factor receptor. TP40 is then internalized and kills these cells by virtue of its
Pseudomonas exotoxin-derived domains. We studied the safety and short-term antitumor activity of intravesical TP40 in 43 patients
with refractory superficial bladder cancer. These patients had resected Ta/T1 disease (n = 19), visible Ta or T1 lesions (n
= 11), or carcinoma in situ (n = 13). Patients were treated with increasing dose levels of TP40 at 0.15, 0.3, 0.6, 1.2, 2.4,
4.8, or 9.6 mg/week for 6 weeks and evaluated by comparing pretreatment and posttreatment cystoscopic examinations, cytology,
and histopathology. All TP40 doses were well tolerated. No evidence of antitumor activity was seen in any of the patients
with Ta or T1 lesions. However, 8 of 9 patients with evaluable carcinoma in situ were judged by histopathology of multiple
biopsy specimens to exhibit clinical improvement following TP40 therapy. In most of these responsive patients, cystoscopic
examination supported the histopathological findings, although cytology of urine and bladder washings persistently demonstrated
malignant cells. Therefore, TP40 appears to be a well-tolerated biological agent that may prove to have utility in treating
carcinoma in situ of the bladder.</description><subject>Aged</subject><subject>Antineoplastic agents</subject><subject>Antineoplastic Agents - adverse effects</subject><subject>Biological and medical sciences</subject><subject>Carcinoma in Situ - drug therapy</subject><subject>Carcinoma in Situ - pathology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Exotoxins - adverse effects</subject><subject>Female</subject><subject>Humans</subject><subject>Immunotherapy</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neoplasm Staging</subject><subject>Pharmacology. Drug treatments</subject><subject>Transforming Growth Factor alpha - adverse effects</subject><subject>Urinary Bladder Neoplasms - drug therapy</subject><subject>Urinary Bladder Neoplasms - pathology</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1995</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9UMtOwzAQjBColMInIPkA3CLZcRy7R1TxqFSJHgrXaLO2iVEexU4E_XsMjdAeZqWZHc3OSTJnQsiUZ4U4jTuVKqU5z86TixA-KGU5o_ksmS0VE0rJefK2rSEYsibYuM4hNCQMoz6Q3pKhNsQb7NvKddANpO-wH_pv15HdNqckYhj3xluHLp5VDWhtPEHo0PjL5MxCE8zVhIvk9fFht3pONy9P69X9Jq1jwCG1ghcalFWIWmaSIjCWMW6oYlTLqhAF0AxQoRWUc0AeM2MuBZeVpsxyvkjujr5733-OJgxl6wKapoHO9GMopVyKXBS_wutJOFat0eXeuxb8oZyKiPzNxEOILVgf33DhX8YLuuR_NrdHWe3e6y_nTXn815tgwGNdsjhC8h_wE3QU</recordid><startdate>19950101</startdate><enddate>19950101</enddate><creator>GOLDBERG, M. R</creator><creator>HEIMBROOK, D. C</creator><creator>CRAWFORD, E. D</creator><creator>OLIFF, A. I</creator><creator>PASTAN, I. H</creator><creator>RUSSO, P</creator><creator>SAROSDY, M. F</creator><creator>GREENBERG, R. E</creator><creator>GIANTONIO, B. J</creator><creator>LINEHAN, W. M</creator><creator>WALTHER, M</creator><creator>FISHER, H. A. G</creator><creator>MESSING, E</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>7X8</scope></search><sort><creationdate>19950101</creationdate><title>Phase I clinical study of the recombinant oncotoxin TP40 in superficial bladder cancer</title><author>GOLDBERG, M. R ; HEIMBROOK, D. C ; CRAWFORD, E. D ; OLIFF, A. I ; PASTAN, I. H ; RUSSO, P ; SAROSDY, M. F ; GREENBERG, R. E ; GIANTONIO, B. J ; LINEHAN, W. M ; WALTHER, M ; FISHER, H. A. G ; MESSING, E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h265t-f536da8f8ccd7270ca11213e0810d7b656a02ac8cf5033ac3887c47537bd01f33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1995</creationdate><topic>Aged</topic><topic>Antineoplastic agents</topic><topic>Antineoplastic Agents - adverse effects</topic><topic>Biological and medical sciences</topic><topic>Carcinoma in Situ - drug therapy</topic><topic>Carcinoma in Situ - pathology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Exotoxins - adverse effects</topic><topic>Female</topic><topic>Humans</topic><topic>Immunotherapy</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Neoplasm Staging</topic><topic>Pharmacology. Drug treatments</topic><topic>Transforming Growth Factor alpha - adverse effects</topic><topic>Urinary Bladder Neoplasms - drug therapy</topic><topic>Urinary Bladder Neoplasms - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>GOLDBERG, M. R</creatorcontrib><creatorcontrib>HEIMBROOK, D. C</creatorcontrib><creatorcontrib>CRAWFORD, E. D</creatorcontrib><creatorcontrib>OLIFF, A. I</creatorcontrib><creatorcontrib>PASTAN, I. H</creatorcontrib><creatorcontrib>RUSSO, P</creatorcontrib><creatorcontrib>SAROSDY, M. F</creatorcontrib><creatorcontrib>GREENBERG, R. E</creatorcontrib><creatorcontrib>GIANTONIO, B. J</creatorcontrib><creatorcontrib>LINEHAN, W. M</creatorcontrib><creatorcontrib>WALTHER, M</creatorcontrib><creatorcontrib>FISHER, H. A. G</creatorcontrib><creatorcontrib>MESSING, E</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>MEDLINE - Academic</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>GOLDBERG, M. R</au><au>HEIMBROOK, D. C</au><au>CRAWFORD, E. D</au><au>OLIFF, A. I</au><au>PASTAN, I. H</au><au>RUSSO, P</au><au>SAROSDY, M. F</au><au>GREENBERG, R. E</au><au>GIANTONIO, B. J</au><au>LINEHAN, W. M</au><au>WALTHER, M</au><au>FISHER, H. A. G</au><au>MESSING, E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phase I clinical study of the recombinant oncotoxin TP40 in superficial bladder cancer</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>1995-01-01</date><risdate>1995</risdate><volume>1</volume><issue>1</issue><spage>57</spage><epage>61</epage><pages>57-61</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Transforming growth factor alpha-Pseudomonas exotoxin-40 (TP40) is a hybrid fusion protein that selectively binds to cancer
cells that express the epidermal growth factor receptor. TP40 is then internalized and kills these cells by virtue of its
Pseudomonas exotoxin-derived domains. We studied the safety and short-term antitumor activity of intravesical TP40 in 43 patients
with refractory superficial bladder cancer. These patients had resected Ta/T1 disease (n = 19), visible Ta or T1 lesions (n
= 11), or carcinoma in situ (n = 13). Patients were treated with increasing dose levels of TP40 at 0.15, 0.3, 0.6, 1.2, 2.4,
4.8, or 9.6 mg/week for 6 weeks and evaluated by comparing pretreatment and posttreatment cystoscopic examinations, cytology,
and histopathology. All TP40 doses were well tolerated. No evidence of antitumor activity was seen in any of the patients
with Ta or T1 lesions. However, 8 of 9 patients with evaluable carcinoma in situ were judged by histopathology of multiple
biopsy specimens to exhibit clinical improvement following TP40 therapy. In most of these responsive patients, cystoscopic
examination supported the histopathological findings, although cytology of urine and bladder washings persistently demonstrated
malignant cells. Therefore, TP40 appears to be a well-tolerated biological agent that may prove to have utility in treating
carcinoma in situ of the bladder.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>9815887</pmid><tpages>5</tpages></addata></record> |
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| source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Aged Antineoplastic agents Antineoplastic Agents - adverse effects Biological and medical sciences Carcinoma in Situ - drug therapy Carcinoma in Situ - pathology Dose-Response Relationship, Drug Exotoxins - adverse effects Female Humans Immunotherapy Male Medical sciences Middle Aged Neoplasm Staging Pharmacology. Drug treatments Transforming Growth Factor alpha - adverse effects Urinary Bladder Neoplasms - drug therapy Urinary Bladder Neoplasms - pathology |
| title | Phase I clinical study of the recombinant oncotoxin TP40 in superficial bladder cancer |
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