Evaluation of irinotecan in combination with 5-fluorouracil or etoposide in xenograft models of colon adenocarcinoma and rhabdomyosarcoma
Irinotecan [7-ethyl-10-(4-[1-piperidino]-1-piperidino)-carbonyloxy-camptothec in] administered i.v. in two courses, each course consisting of administration every day for 5 days [(dx5)2] on days 1-5 and 8-12, has demonstrated significant activity against advanced human tumor xenografts derived from...
Gespeichert in:
| Veröffentlicht in: | Clinical cancer research 1996-01, Vol.2 (1), p.107-118 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 118 |
|---|---|
| container_issue | 1 |
| container_start_page | 107 |
| container_title | Clinical cancer research |
| container_volume | 2 |
| creator | J A Houghton P J Cheshire J D Hallman, 2nd L Lutz X Luo Y Li P J Houghton |
| description | Irinotecan [7-ethyl-10-(4-[1-piperidino]-1-piperidino)-carbonyloxy-camptothec in] administered i.v. in two courses, each course
consisting of administration every day for 5 days [(dx5)2] on days 1-5 and 8-12, has demonstrated significant activity against
advanced human tumor xenografts derived from colon adenocarcinomas and several childhood cancers. To build on this therapy,
we have evaluated the combination of irinotecan given on this schedule with 5-fluorouracil given on days 1, 7, and 14 with
or without leucovorin [(dx5)3 i.v.] against colon tumors, or combined with etoposide administered (dx5)2 i.v. either 2 h before
or 2 h after irinotecan for treatment of colon tumors and rhabdomyosarcomas. A combination of 5-fluorouracil at 75% and irinotecan
at 50% of their respective maximum tolerated doses when administered as single agents on this schedule gave acceptable toxicity.
Against colon adenocarcinoma xenografts, 5-fluorouracil did not enhance the response rate compared with that obtained with
the optimum dose of irinotecan given as a single agent. Against GC3/TK- xenografts, which lack thymidine kinase and cannot
salvage thymidine to circumvent the inhibition of thymidylate synthase, the addition of leucovorin to the combination increased
the complete response rate from 10 to >90%, whereas the response rates for the optimal doses of irinotecan or 5-fluorouracil,
as single agents, were 30 and |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_pasca</sourceid><recordid>TN_cdi_pubmed_primary_9816097</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>9816097</sourcerecordid><originalsourceid>FETCH-LOGICAL-h266t-112068f5199b4e88dedb2da55cd2f8f96f95f8c11a1ad969ea0918b68305b413</originalsourceid><addsrcrecordid>eNo9kM1qwzAQhE1pSdO0j1DQofRmkGRLkY4lpD8Q6CV3s9ZPrGJLQbKb5hH61lVI6GmX-WYHdq6KOWFsWVaUs-u846UocV3R2-IupS-MSU1wPStmUhCO5XJe_K6_oZ9gdMGjYJGLzofRKPDIeaTC0Dp_hgc3doiVtp9CDFME5XoUIjJj2IfktDn5f4wPuwh2REPQpk-nRBX6fA06IwVR5fgBEHiNYgetDsMxpCxn8b64sdAn83CZi2L7ut6u3svN59vH6mVTdpTzsSSEYi4sI1K2tRFCG91SDYwpTa2wklvJrFCEAAEtuTSAJREtFxVmbU2qRfF4jt1P7WB0s49ugHhsLo1k_nThkBT0NoJXLv3bqGS5Tpptz2db53bdwUXT5M6UidEkk__pGtqQJtdf_QFN63ui</addsrcrecordid><sourcetype>Index Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Evaluation of irinotecan in combination with 5-fluorouracil or etoposide in xenograft models of colon adenocarcinoma and rhabdomyosarcoma</title><source>MEDLINE</source><source>American Association for Cancer Research</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>J A Houghton ; P J Cheshire ; J D Hallman, 2nd ; L Lutz ; X Luo ; Y Li ; P J Houghton</creator><creatorcontrib>J A Houghton ; P J Cheshire ; J D Hallman, 2nd ; L Lutz ; X Luo ; Y Li ; P J Houghton</creatorcontrib><description>Irinotecan [7-ethyl-10-(4-[1-piperidino]-1-piperidino)-carbonyloxy-camptothec in] administered i.v. in two courses, each course
consisting of administration every day for 5 days [(dx5)2] on days 1-5 and 8-12, has demonstrated significant activity against
advanced human tumor xenografts derived from colon adenocarcinomas and several childhood cancers. To build on this therapy,
we have evaluated the combination of irinotecan given on this schedule with 5-fluorouracil given on days 1, 7, and 14 with
or without leucovorin [(dx5)3 i.v.] against colon tumors, or combined with etoposide administered (dx5)2 i.v. either 2 h before
or 2 h after irinotecan for treatment of colon tumors and rhabdomyosarcomas. A combination of 5-fluorouracil at 75% and irinotecan
at 50% of their respective maximum tolerated doses when administered as single agents on this schedule gave acceptable toxicity.
Against colon adenocarcinoma xenografts, 5-fluorouracil did not enhance the response rate compared with that obtained with
the optimum dose of irinotecan given as a single agent. Against GC3/TK- xenografts, which lack thymidine kinase and cannot
salvage thymidine to circumvent the inhibition of thymidylate synthase, the addition of leucovorin to the combination increased
the complete response rate from 10 to >90%, whereas the response rates for the optimal doses of irinotecan or 5-fluorouracil,
as single agents, were 30 and <10%, respectively. Etoposide d x 5 i.v. for two or three courses or (d x 5)3 p.o. did not cause
objective regression of any colon tumors. In contrast, three of five rhabdomyosarcoma lines demonstrated a high frequency
of partial regressions or complete regressions when treated (d x 5)1 i.v. Repetitive courses [e.g., (d x 5)2 or (d x 5)3]
i.v. or p.o. or by 4-h infusion d x3 i.v. were either equally effective or less effective. Irinotecan and etoposide were combined
using the (d x 5)2 i.v. schedule for both drugs, in which irinotecan was given 2 h before or 2 h after the administration
of etoposide. Each drug could be combined at only 38% of its respective maximum tolerated dose when administered as a single
agent, indicating greater than additive toxicity. Toxicity was similar irrespective of the sequence of administration and
was manifested by loss of weight (73% of the initial weight, nadir day 7), myelosuppression, and prolonged thrombocytopenia.
The responses of colon carcinomas to the combination given in either sequence were similar to that achieved with irinotecan
given alone at the same dose as used in the combination. Similarly, when etoposide was given before irinotecan, the responses
of rhabdomyosarcomas were similar to those for irinotecan. However, in experiments in which etoposide was administered 2 h
after each dose of irinotecan, there was significant antagonism of the antitumor activity of irinotecan.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>PMID: 9816097</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Adenocarcinoma - drug therapy ; Animals ; Antineoplastic agents ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Biological and medical sciences ; Camptothecin - administration & dosage ; Camptothecin - analogs & derivatives ; Camptothecin - toxicity ; Chemotherapy ; Colonic Neoplasms - drug therapy ; Etoposide - administration & dosage ; Female ; Fluorouracil - administration & dosage ; Humans ; Medical sciences ; Mice ; Mice, Inbred CBA ; Neoplasm Transplantation ; Pharmacology. Drug treatments ; Rhabdomyosarcoma - drug therapy ; Transplantation, Heterologous</subject><ispartof>Clinical cancer research, 1996-01, Vol.2 (1), p.107-118</ispartof><rights>1996 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=2954322$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9816097$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>J A Houghton</creatorcontrib><creatorcontrib>P J Cheshire</creatorcontrib><creatorcontrib>J D Hallman, 2nd</creatorcontrib><creatorcontrib>L Lutz</creatorcontrib><creatorcontrib>X Luo</creatorcontrib><creatorcontrib>Y Li</creatorcontrib><creatorcontrib>P J Houghton</creatorcontrib><title>Evaluation of irinotecan in combination with 5-fluorouracil or etoposide in xenograft models of colon adenocarcinoma and rhabdomyosarcoma</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Irinotecan [7-ethyl-10-(4-[1-piperidino]-1-piperidino)-carbonyloxy-camptothec in] administered i.v. in two courses, each course
consisting of administration every day for 5 days [(dx5)2] on days 1-5 and 8-12, has demonstrated significant activity against
advanced human tumor xenografts derived from colon adenocarcinomas and several childhood cancers. To build on this therapy,
we have evaluated the combination of irinotecan given on this schedule with 5-fluorouracil given on days 1, 7, and 14 with
or without leucovorin [(dx5)3 i.v.] against colon tumors, or combined with etoposide administered (dx5)2 i.v. either 2 h before
or 2 h after irinotecan for treatment of colon tumors and rhabdomyosarcomas. A combination of 5-fluorouracil at 75% and irinotecan
at 50% of their respective maximum tolerated doses when administered as single agents on this schedule gave acceptable toxicity.
Against colon adenocarcinoma xenografts, 5-fluorouracil did not enhance the response rate compared with that obtained with
the optimum dose of irinotecan given as a single agent. Against GC3/TK- xenografts, which lack thymidine kinase and cannot
salvage thymidine to circumvent the inhibition of thymidylate synthase, the addition of leucovorin to the combination increased
the complete response rate from 10 to >90%, whereas the response rates for the optimal doses of irinotecan or 5-fluorouracil,
as single agents, were 30 and <10%, respectively. Etoposide d x 5 i.v. for two or three courses or (d x 5)3 p.o. did not cause
objective regression of any colon tumors. In contrast, three of five rhabdomyosarcoma lines demonstrated a high frequency
of partial regressions or complete regressions when treated (d x 5)1 i.v. Repetitive courses [e.g., (d x 5)2 or (d x 5)3]
i.v. or p.o. or by 4-h infusion d x3 i.v. were either equally effective or less effective. Irinotecan and etoposide were combined
using the (d x 5)2 i.v. schedule for both drugs, in which irinotecan was given 2 h before or 2 h after the administration
of etoposide. Each drug could be combined at only 38% of its respective maximum tolerated dose when administered as a single
agent, indicating greater than additive toxicity. Toxicity was similar irrespective of the sequence of administration and
was manifested by loss of weight (73% of the initial weight, nadir day 7), myelosuppression, and prolonged thrombocytopenia.
The responses of colon carcinomas to the combination given in either sequence were similar to that achieved with irinotecan
given alone at the same dose as used in the combination. Similarly, when etoposide was given before irinotecan, the responses
of rhabdomyosarcomas were similar to those for irinotecan. However, in experiments in which etoposide was administered 2 h
after each dose of irinotecan, there was significant antagonism of the antitumor activity of irinotecan.</description><subject>Adenocarcinoma - drug therapy</subject><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Camptothecin - administration & dosage</subject><subject>Camptothecin - analogs & derivatives</subject><subject>Camptothecin - toxicity</subject><subject>Chemotherapy</subject><subject>Colonic Neoplasms - drug therapy</subject><subject>Etoposide - administration & dosage</subject><subject>Female</subject><subject>Fluorouracil - administration & dosage</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred CBA</subject><subject>Neoplasm Transplantation</subject><subject>Pharmacology. Drug treatments</subject><subject>Rhabdomyosarcoma - drug therapy</subject><subject>Transplantation, Heterologous</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kM1qwzAQhE1pSdO0j1DQofRmkGRLkY4lpD8Q6CV3s9ZPrGJLQbKb5hH61lVI6GmX-WYHdq6KOWFsWVaUs-u846UocV3R2-IupS-MSU1wPStmUhCO5XJe_K6_oZ9gdMGjYJGLzofRKPDIeaTC0Dp_hgc3doiVtp9CDFME5XoUIjJj2IfktDn5f4wPuwh2REPQpk-nRBX6fA06IwVR5fgBEHiNYgetDsMxpCxn8b64sdAn83CZi2L7ut6u3svN59vH6mVTdpTzsSSEYi4sI1K2tRFCG91SDYwpTa2wklvJrFCEAAEtuTSAJREtFxVmbU2qRfF4jt1P7WB0s49ugHhsLo1k_nThkBT0NoJXLv3bqGS5Tpptz2db53bdwUXT5M6UidEkk__pGtqQJtdf_QFN63ui</recordid><startdate>19960101</startdate><enddate>19960101</enddate><creator>J A Houghton</creator><creator>P J Cheshire</creator><creator>J D Hallman, 2nd</creator><creator>L Lutz</creator><creator>X Luo</creator><creator>Y Li</creator><creator>P J Houghton</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></search><sort><creationdate>19960101</creationdate><title>Evaluation of irinotecan in combination with 5-fluorouracil or etoposide in xenograft models of colon adenocarcinoma and rhabdomyosarcoma</title><author>J A Houghton ; P J Cheshire ; J D Hallman, 2nd ; L Lutz ; X Luo ; Y Li ; P J Houghton</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h266t-112068f5199b4e88dedb2da55cd2f8f96f95f8c11a1ad969ea0918b68305b413</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Adenocarcinoma - drug therapy</topic><topic>Animals</topic><topic>Antineoplastic agents</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Camptothecin - administration & dosage</topic><topic>Camptothecin - analogs & derivatives</topic><topic>Camptothecin - toxicity</topic><topic>Chemotherapy</topic><topic>Colonic Neoplasms - drug therapy</topic><topic>Etoposide - administration & dosage</topic><topic>Female</topic><topic>Fluorouracil - administration & dosage</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred CBA</topic><topic>Neoplasm Transplantation</topic><topic>Pharmacology. Drug treatments</topic><topic>Rhabdomyosarcoma - drug therapy</topic><topic>Transplantation, Heterologous</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>J A Houghton</creatorcontrib><creatorcontrib>P J Cheshire</creatorcontrib><creatorcontrib>J D Hallman, 2nd</creatorcontrib><creatorcontrib>L Lutz</creatorcontrib><creatorcontrib>X Luo</creatorcontrib><creatorcontrib>Y Li</creatorcontrib><creatorcontrib>P J Houghton</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>J A Houghton</au><au>P J Cheshire</au><au>J D Hallman, 2nd</au><au>L Lutz</au><au>X Luo</au><au>Y Li</au><au>P J Houghton</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of irinotecan in combination with 5-fluorouracil or etoposide in xenograft models of colon adenocarcinoma and rhabdomyosarcoma</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>1996-01-01</date><risdate>1996</risdate><volume>2</volume><issue>1</issue><spage>107</spage><epage>118</epage><pages>107-118</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Irinotecan [7-ethyl-10-(4-[1-piperidino]-1-piperidino)-carbonyloxy-camptothec in] administered i.v. in two courses, each course
consisting of administration every day for 5 days [(dx5)2] on days 1-5 and 8-12, has demonstrated significant activity against
advanced human tumor xenografts derived from colon adenocarcinomas and several childhood cancers. To build on this therapy,
we have evaluated the combination of irinotecan given on this schedule with 5-fluorouracil given on days 1, 7, and 14 with
or without leucovorin [(dx5)3 i.v.] against colon tumors, or combined with etoposide administered (dx5)2 i.v. either 2 h before
or 2 h after irinotecan for treatment of colon tumors and rhabdomyosarcomas. A combination of 5-fluorouracil at 75% and irinotecan
at 50% of their respective maximum tolerated doses when administered as single agents on this schedule gave acceptable toxicity.
Against colon adenocarcinoma xenografts, 5-fluorouracil did not enhance the response rate compared with that obtained with
the optimum dose of irinotecan given as a single agent. Against GC3/TK- xenografts, which lack thymidine kinase and cannot
salvage thymidine to circumvent the inhibition of thymidylate synthase, the addition of leucovorin to the combination increased
the complete response rate from 10 to >90%, whereas the response rates for the optimal doses of irinotecan or 5-fluorouracil,
as single agents, were 30 and <10%, respectively. Etoposide d x 5 i.v. for two or three courses or (d x 5)3 p.o. did not cause
objective regression of any colon tumors. In contrast, three of five rhabdomyosarcoma lines demonstrated a high frequency
of partial regressions or complete regressions when treated (d x 5)1 i.v. Repetitive courses [e.g., (d x 5)2 or (d x 5)3]
i.v. or p.o. or by 4-h infusion d x3 i.v. were either equally effective or less effective. Irinotecan and etoposide were combined
using the (d x 5)2 i.v. schedule for both drugs, in which irinotecan was given 2 h before or 2 h after the administration
of etoposide. Each drug could be combined at only 38% of its respective maximum tolerated dose when administered as a single
agent, indicating greater than additive toxicity. Toxicity was similar irrespective of the sequence of administration and
was manifested by loss of weight (73% of the initial weight, nadir day 7), myelosuppression, and prolonged thrombocytopenia.
The responses of colon carcinomas to the combination given in either sequence were similar to that achieved with irinotecan
given alone at the same dose as used in the combination. Similarly, when etoposide was given before irinotecan, the responses
of rhabdomyosarcomas were similar to those for irinotecan. However, in experiments in which etoposide was administered 2 h
after each dose of irinotecan, there was significant antagonism of the antitumor activity of irinotecan.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>9816097</pmid><tpages>12</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1078-0432 |
| ispartof | Clinical cancer research, 1996-01, Vol.2 (1), p.107-118 |
| issn | 1078-0432 1557-3265 |
| language | eng |
| recordid | cdi_pubmed_primary_9816097 |
| source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adenocarcinoma - drug therapy Animals Antineoplastic agents Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biological and medical sciences Camptothecin - administration & dosage Camptothecin - analogs & derivatives Camptothecin - toxicity Chemotherapy Colonic Neoplasms - drug therapy Etoposide - administration & dosage Female Fluorouracil - administration & dosage Humans Medical sciences Mice Mice, Inbred CBA Neoplasm Transplantation Pharmacology. Drug treatments Rhabdomyosarcoma - drug therapy Transplantation, Heterologous |
| title | Evaluation of irinotecan in combination with 5-fluorouracil or etoposide in xenograft models of colon adenocarcinoma and rhabdomyosarcoma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-29T01%3A28%3A56IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmed_pasca&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Evaluation%20of%20irinotecan%20in%20combination%20with%205-fluorouracil%20or%20etoposide%20in%20xenograft%20models%20of%20colon%20adenocarcinoma%20and%20rhabdomyosarcoma&rft.jtitle=Clinical%20cancer%20research&rft.au=J%20A%20Houghton&rft.date=1996-01-01&rft.volume=2&rft.issue=1&rft.spage=107&rft.epage=118&rft.pages=107-118&rft.issn=1078-0432&rft.eissn=1557-3265&rft_id=info:doi/&rft_dat=%3Cpubmed_pasca%3E9816097%3C/pubmed_pasca%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/9816097&rfr_iscdi=true |