A Dose-Escalating Study of Weekly Bolus Topotecan in Previously Treated Ovarian Cancer Patients
Objective. Topotecan is an established topoisomerase I inhibitor for the treatment of relapsed ovarian cancer. Myelotoxicity and suboptimal patient convenience associated with daily topotecan, however, have prompted investigators to explore alternate regimens, including a weekly regimen of topotecan...
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| Veröffentlicht in: | Gynecologic oncology 2001-11, Vol.83 (2), p.394-399 |
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| creator | Homesley, Howard D. Hall, Don J. Martin, David A. Lewandowski, George S. Vaccarello, Luis Nahhas, William A. Suggs, Charles L. Penley, Rebecca G. |
| description | Objective. Topotecan is an established topoisomerase I inhibitor for the treatment of relapsed ovarian cancer. Myelotoxicity and suboptimal patient convenience associated with daily topotecan, however, have prompted investigators to explore alternate regimens, including a weekly regimen of topotecan. The objective of this study was to determine the maximum tolerated dose (MTD) of topotecan given as a weekly bolus in previously treated ovarian cancer patients.
Methods. Second- and third-line ovarian cancer patients with measurable disease or elevated cancer antigen 125 received weekly bolus topotecan intravenously starting at 1.5 mg/m2. Topotecan was escalated in dose increments of 0.5 mg/m2 every 21 days as tolerability allowed. Dose-limiting toxicity was defined as grade 3/4 neutropenia or thrombocytopenia.
Results. Thirty-two of 35 patients were evaluable for safety and tolerability. No notable toxicity was observed with weekly topotecan doses 2 mg/m2.
Conclusions. The establishment of a well-tolerated, weekly regimen of topotecan (4 mg/m2, with a maximum recommended dose of 6 mg/m2) provides the basis for further investigation in phase II studies of single-agent and combination regimens in previously treated ovarian cancer patients. |
| doi_str_mv | 10.1006/gyno.2001.6435 |
| format | Article |
| fullrecord | <record><control><sourceid>elsevier_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1006_gyno_2001_6435</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0090825801964352</els_id><sourcerecordid>S0090825801964352</sourcerecordid><originalsourceid>FETCH-LOGICAL-c370t-539dc8a0890bab09e6623d4fd2336f7f5bd6c546ce3cdff884e77ab06ea661113</originalsourceid><addsrcrecordid>eNp1kEFrGzEQRkVoSNwk1xyLLj2uO1qttNqj6yZpweBAHHIUsjQKSu2VkdYG__tqsSGnnuYw7xvme4TcM5gyAPnj_djHaQ3AprLh4oJMGHSikkp0X8gEoINK1UJdk685fwAAB1ZfkWvGJEgGfEL0jP6KGauHbM3GDKF_py_D3h1p9PQN8e_mSH_GzT7TVdzFAa3paejpc8JDiPtctquEZkBHlweTQtnOTW8x0edyC_sh35JLbzYZ787zhrw-Pqzmv6vF8unPfLaoLG9hqATvnFUGVAdrs4YOpay5a7yrOZe-9WLtpBWNtMit816pBtu2gBKNlIwxfkOmp7s2xZwTer1LYWvSUTPQoyk9mtKjKT2aKoFvp8Buv96i-8TPagrw_QyY0Y1PpVjIn1zDhBKyLZw6cVjqHQImnW2pbtGFhHbQLob__fAPMf6FXA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>A Dose-Escalating Study of Weekly Bolus Topotecan in Previously Treated Ovarian Cancer Patients</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><creator>Homesley, Howard D. ; Hall, Don J. ; Martin, David A. ; Lewandowski, George S. ; Vaccarello, Luis ; Nahhas, William A. ; Suggs, Charles L. ; Penley, Rebecca G.</creator><creatorcontrib>Homesley, Howard D. ; Hall, Don J. ; Martin, David A. ; Lewandowski, George S. ; Vaccarello, Luis ; Nahhas, William A. ; Suggs, Charles L. ; Penley, Rebecca G.</creatorcontrib><description>Objective. Topotecan is an established topoisomerase I inhibitor for the treatment of relapsed ovarian cancer. Myelotoxicity and suboptimal patient convenience associated with daily topotecan, however, have prompted investigators to explore alternate regimens, including a weekly regimen of topotecan. The objective of this study was to determine the maximum tolerated dose (MTD) of topotecan given as a weekly bolus in previously treated ovarian cancer patients.
Methods. Second- and third-line ovarian cancer patients with measurable disease or elevated cancer antigen 125 received weekly bolus topotecan intravenously starting at 1.5 mg/m2. Topotecan was escalated in dose increments of 0.5 mg/m2 every 21 days as tolerability allowed. Dose-limiting toxicity was defined as grade 3/4 neutropenia or thrombocytopenia.
Results. Thirty-two of 35 patients were evaluable for safety and tolerability. No notable toxicity was observed with weekly topotecan doses <4 mg/m2. Additionally, there was an absence of dose-limiting myelotoxicity and thrombocytopenia with weekly topotecan. The MTD of weekly topotecan without the use of granulocyte colony-stimulating factor support was 4 mg/m2, with grade 2 anemia, chronic fatigue, and grade 2 gastrointestinal toxicity limiting further dose escalation. Weekly topotecan also demonstrated antitumor activity at doses >2 mg/m2.
Conclusions. The establishment of a well-tolerated, weekly regimen of topotecan (4 mg/m2, with a maximum recommended dose of 6 mg/m2) provides the basis for further investigation in phase II studies of single-agent and combination regimens in previously treated ovarian cancer patients.</description><identifier>ISSN: 0090-8258</identifier><identifier>EISSN: 1095-6859</identifier><identifier>DOI: 10.1006/gyno.2001.6435</identifier><identifier>PMID: 11606103</identifier><identifier>CODEN: GYNOA3</identifier><language>eng</language><publisher>San Diego, CA: Elsevier Inc</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Antineoplastic agents ; Antineoplastic Agents - adverse effects ; Antineoplastic Agents - therapeutic use ; Biological and medical sciences ; cancer antigen 125 ; Chemotherapy ; dose escalation ; dose-limiting tolerability ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Enzyme Inhibitors - adverse effects ; Enzyme Inhibitors - therapeutic use ; Female ; Humans ; Medical sciences ; Middle Aged ; myelotoxicity ; ovarian cancer ; Ovarian Neoplasms - drug therapy ; Pharmacology. Drug treatments ; topoisomerase I ; topotecan ; Topotecan - adverse effects ; Topotecan - therapeutic use</subject><ispartof>Gynecologic oncology, 2001-11, Vol.83 (2), p.394-399</ispartof><rights>2001 Academic Press</rights><rights>2002 INIST-CNRS</rights><rights>Copyright 2001 Academic Press.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c370t-539dc8a0890bab09e6623d4fd2336f7f5bd6c546ce3cdff884e77ab06ea661113</citedby><cites>FETCH-LOGICAL-c370t-539dc8a0890bab09e6623d4fd2336f7f5bd6c546ce3cdff884e77ab06ea661113</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1006/gyno.2001.6435$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14158567$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11606103$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Homesley, Howard D.</creatorcontrib><creatorcontrib>Hall, Don J.</creatorcontrib><creatorcontrib>Martin, David A.</creatorcontrib><creatorcontrib>Lewandowski, George S.</creatorcontrib><creatorcontrib>Vaccarello, Luis</creatorcontrib><creatorcontrib>Nahhas, William A.</creatorcontrib><creatorcontrib>Suggs, Charles L.</creatorcontrib><creatorcontrib>Penley, Rebecca G.</creatorcontrib><title>A Dose-Escalating Study of Weekly Bolus Topotecan in Previously Treated Ovarian Cancer Patients</title><title>Gynecologic oncology</title><addtitle>Gynecol Oncol</addtitle><description>Objective. Topotecan is an established topoisomerase I inhibitor for the treatment of relapsed ovarian cancer. Myelotoxicity and suboptimal patient convenience associated with daily topotecan, however, have prompted investigators to explore alternate regimens, including a weekly regimen of topotecan. The objective of this study was to determine the maximum tolerated dose (MTD) of topotecan given as a weekly bolus in previously treated ovarian cancer patients.
Methods. Second- and third-line ovarian cancer patients with measurable disease or elevated cancer antigen 125 received weekly bolus topotecan intravenously starting at 1.5 mg/m2. Topotecan was escalated in dose increments of 0.5 mg/m2 every 21 days as tolerability allowed. Dose-limiting toxicity was defined as grade 3/4 neutropenia or thrombocytopenia.
Results. Thirty-two of 35 patients were evaluable for safety and tolerability. No notable toxicity was observed with weekly topotecan doses <4 mg/m2. Additionally, there was an absence of dose-limiting myelotoxicity and thrombocytopenia with weekly topotecan. The MTD of weekly topotecan without the use of granulocyte colony-stimulating factor support was 4 mg/m2, with grade 2 anemia, chronic fatigue, and grade 2 gastrointestinal toxicity limiting further dose escalation. Weekly topotecan also demonstrated antitumor activity at doses >2 mg/m2.
Conclusions. The establishment of a well-tolerated, weekly regimen of topotecan (4 mg/m2, with a maximum recommended dose of 6 mg/m2) provides the basis for further investigation in phase II studies of single-agent and combination regimens in previously treated ovarian cancer patients.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antineoplastic agents</subject><subject>Antineoplastic Agents - adverse effects</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>cancer antigen 125</subject><subject>Chemotherapy</subject><subject>dose escalation</subject><subject>dose-limiting tolerability</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Administration Schedule</subject><subject>Enzyme Inhibitors - adverse effects</subject><subject>Enzyme Inhibitors - therapeutic use</subject><subject>Female</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>myelotoxicity</subject><subject>ovarian cancer</subject><subject>Ovarian Neoplasms - drug therapy</subject><subject>Pharmacology. Drug treatments</subject><subject>topoisomerase I</subject><subject>topotecan</subject><subject>Topotecan - adverse effects</subject><subject>Topotecan - therapeutic use</subject><issn>0090-8258</issn><issn>1095-6859</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kEFrGzEQRkVoSNwk1xyLLj2uO1qttNqj6yZpweBAHHIUsjQKSu2VkdYG__tqsSGnnuYw7xvme4TcM5gyAPnj_djHaQ3AprLh4oJMGHSikkp0X8gEoINK1UJdk685fwAAB1ZfkWvGJEgGfEL0jP6KGauHbM3GDKF_py_D3h1p9PQN8e_mSH_GzT7TVdzFAa3paejpc8JDiPtctquEZkBHlweTQtnOTW8x0edyC_sh35JLbzYZ787zhrw-Pqzmv6vF8unPfLaoLG9hqATvnFUGVAdrs4YOpay5a7yrOZe-9WLtpBWNtMit816pBtu2gBKNlIwxfkOmp7s2xZwTer1LYWvSUTPQoyk9mtKjKT2aKoFvp8Buv96i-8TPagrw_QyY0Y1PpVjIn1zDhBKyLZw6cVjqHQImnW2pbtGFhHbQLob__fAPMf6FXA</recordid><startdate>20011101</startdate><enddate>20011101</enddate><creator>Homesley, Howard D.</creator><creator>Hall, Don J.</creator><creator>Martin, David A.</creator><creator>Lewandowski, George S.</creator><creator>Vaccarello, Luis</creator><creator>Nahhas, William A.</creator><creator>Suggs, Charles L.</creator><creator>Penley, Rebecca G.</creator><general>Elsevier Inc</general><general>Elsevier</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></search><sort><creationdate>20011101</creationdate><title>A Dose-Escalating Study of Weekly Bolus Topotecan in Previously Treated Ovarian Cancer Patients</title><author>Homesley, Howard D. ; Hall, Don J. ; Martin, David A. ; Lewandowski, George S. ; Vaccarello, Luis ; Nahhas, William A. ; Suggs, Charles L. ; Penley, Rebecca G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c370t-539dc8a0890bab09e6623d4fd2336f7f5bd6c546ce3cdff884e77ab06ea661113</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antineoplastic agents</topic><topic>Antineoplastic Agents - adverse effects</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>cancer antigen 125</topic><topic>Chemotherapy</topic><topic>dose escalation</topic><topic>dose-limiting tolerability</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Administration Schedule</topic><topic>Enzyme Inhibitors - adverse effects</topic><topic>Enzyme Inhibitors - therapeutic use</topic><topic>Female</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>myelotoxicity</topic><topic>ovarian cancer</topic><topic>Ovarian Neoplasms - drug therapy</topic><topic>Pharmacology. Drug treatments</topic><topic>topoisomerase I</topic><topic>topotecan</topic><topic>Topotecan - adverse effects</topic><topic>Topotecan - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Homesley, Howard D.</creatorcontrib><creatorcontrib>Hall, Don J.</creatorcontrib><creatorcontrib>Martin, David A.</creatorcontrib><creatorcontrib>Lewandowski, George S.</creatorcontrib><creatorcontrib>Vaccarello, Luis</creatorcontrib><creatorcontrib>Nahhas, William A.</creatorcontrib><creatorcontrib>Suggs, Charles L.</creatorcontrib><creatorcontrib>Penley, Rebecca G.</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><jtitle>Gynecologic oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Homesley, Howard D.</au><au>Hall, Don J.</au><au>Martin, David A.</au><au>Lewandowski, George S.</au><au>Vaccarello, Luis</au><au>Nahhas, William A.</au><au>Suggs, Charles L.</au><au>Penley, Rebecca G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Dose-Escalating Study of Weekly Bolus Topotecan in Previously Treated Ovarian Cancer Patients</atitle><jtitle>Gynecologic oncology</jtitle><addtitle>Gynecol Oncol</addtitle><date>2001-11-01</date><risdate>2001</risdate><volume>83</volume><issue>2</issue><spage>394</spage><epage>399</epage><pages>394-399</pages><issn>0090-8258</issn><eissn>1095-6859</eissn><coden>GYNOA3</coden><abstract>Objective. Topotecan is an established topoisomerase I inhibitor for the treatment of relapsed ovarian cancer. Myelotoxicity and suboptimal patient convenience associated with daily topotecan, however, have prompted investigators to explore alternate regimens, including a weekly regimen of topotecan. The objective of this study was to determine the maximum tolerated dose (MTD) of topotecan given as a weekly bolus in previously treated ovarian cancer patients.
Methods. Second- and third-line ovarian cancer patients with measurable disease or elevated cancer antigen 125 received weekly bolus topotecan intravenously starting at 1.5 mg/m2. Topotecan was escalated in dose increments of 0.5 mg/m2 every 21 days as tolerability allowed. Dose-limiting toxicity was defined as grade 3/4 neutropenia or thrombocytopenia.
Results. Thirty-two of 35 patients were evaluable for safety and tolerability. No notable toxicity was observed with weekly topotecan doses <4 mg/m2. Additionally, there was an absence of dose-limiting myelotoxicity and thrombocytopenia with weekly topotecan. The MTD of weekly topotecan without the use of granulocyte colony-stimulating factor support was 4 mg/m2, with grade 2 anemia, chronic fatigue, and grade 2 gastrointestinal toxicity limiting further dose escalation. Weekly topotecan also demonstrated antitumor activity at doses >2 mg/m2.
Conclusions. The establishment of a well-tolerated, weekly regimen of topotecan (4 mg/m2, with a maximum recommended dose of 6 mg/m2) provides the basis for further investigation in phase II studies of single-agent and combination regimens in previously treated ovarian cancer patients.</abstract><cop>San Diego, CA</cop><pub>Elsevier Inc</pub><pmid>11606103</pmid><doi>10.1006/gyno.2001.6435</doi><tpages>6</tpages></addata></record> |
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| ispartof | Gynecologic oncology, 2001-11, Vol.83 (2), p.394-399 |
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| subjects | Adult Aged Aged, 80 and over Antineoplastic agents Antineoplastic Agents - adverse effects Antineoplastic Agents - therapeutic use Biological and medical sciences cancer antigen 125 Chemotherapy dose escalation dose-limiting tolerability Dose-Response Relationship, Drug Drug Administration Schedule Enzyme Inhibitors - adverse effects Enzyme Inhibitors - therapeutic use Female Humans Medical sciences Middle Aged myelotoxicity ovarian cancer Ovarian Neoplasms - drug therapy Pharmacology. Drug treatments topoisomerase I topotecan Topotecan - adverse effects Topotecan - therapeutic use |
| title | A Dose-Escalating Study of Weekly Bolus Topotecan in Previously Treated Ovarian Cancer Patients |
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