Comparison of 5-day MTX and 5-day ETP treatment results and early predictors of drug resistance to 5-day MTX in patients with post-molar low-risk gestational trophoblastic neoplasia

Abstract Objective To determine the primary remission rates and predictors of drug resistance in patients with post-molar low-risk gestational trophoblastic neoplasia (GTN) who were treated with a 5-day intramuscular methotrexate (5-day IM MTX) or a 5-day drip infusion etoposide (5-day DIV ETP) regi...

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Veröffentlicht in:Gynecologic oncology 2015-12, Vol.139 (3), p.429-432
Hauptverfasser: Kizaki, Shoko, Hashimoto, Kazunori, Matsui, Hideo, Usui, Hirokazu, Shozu, Makio
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container_end_page 432
container_issue 3
container_start_page 429
container_title Gynecologic oncology
container_volume 139
creator Kizaki, Shoko
Hashimoto, Kazunori
Matsui, Hideo
Usui, Hirokazu
Shozu, Makio
description Abstract Objective To determine the primary remission rates and predictors of drug resistance in patients with post-molar low-risk gestational trophoblastic neoplasia (GTN) who were treated with a 5-day intramuscular methotrexate (5-day IM MTX) or a 5-day drip infusion etoposide (5-day DIV ETP) regimen. Methods Between 1980 and 2014, 166 consecutive patients with low-risk post-molar GTN were initially treated with a 5-day IM MTX or a 5-day DIV ETP regimen. The primary remission rates, changes in chemotherapy due to drug resistance or toxicity, and relapse rates were compared. Furthermore, we analyzed the factors that influenced the development of resistance to MTX. Results Primary remission rates were significantly higher among the ETP-treated patients than among the MTX-treated patients. Among the 42 patients who required a change in chemotherapy, 23 patients (22.6%) and 4 patients (6.3%) were diagnosed as being resistant to MTX and EPT, respectively. Maternal age and the presence of metastasis did not significantly influence the development of MTX resistance, although higher FIGO scores and pre-treatment human chorionic gonadotropin (hCG) levels of > 5 × 104 mIU/mL were significantly more common among patients who developed MTX resistance. Moreover, a < 30% decrease in hCG after the first cycles of MTX chemotherapy was significantly associated with the development of MTX resistance. Conclusions All patients with low-risk GTN eventually achieved complete remission, although several patients developed drug resistance to the first-line chemotherapy. A < 30% decrease in hCG during the first chemotherapy cycle may be an early indicator of drug resistance after commencing a 5-day MTX regimen.
doi_str_mv 10.1016/j.ygyno.2015.10.007
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Methods Between 1980 and 2014, 166 consecutive patients with low-risk post-molar GTN were initially treated with a 5-day IM MTX or a 5-day DIV ETP regimen. The primary remission rates, changes in chemotherapy due to drug resistance or toxicity, and relapse rates were compared. Furthermore, we analyzed the factors that influenced the development of resistance to MTX. Results Primary remission rates were significantly higher among the ETP-treated patients than among the MTX-treated patients. Among the 42 patients who required a change in chemotherapy, 23 patients (22.6%) and 4 patients (6.3%) were diagnosed as being resistant to MTX and EPT, respectively. Maternal age and the presence of metastasis did not significantly influence the development of MTX resistance, although higher FIGO scores and pre-treatment human chorionic gonadotropin (hCG) levels of &gt; 5 × 104 mIU/mL were significantly more common among patients who developed MTX resistance. Moreover, a &lt; 30% decrease in hCG after the first cycles of MTX chemotherapy was significantly associated with the development of MTX resistance. Conclusions All patients with low-risk GTN eventually achieved complete remission, although several patients developed drug resistance to the first-line chemotherapy. A &lt; 30% decrease in hCG during the first chemotherapy cycle may be an early indicator of drug resistance after commencing a 5-day MTX regimen.</description><identifier>ISSN: 0090-8258</identifier><identifier>EISSN: 1095-6859</identifier><identifier>DOI: 10.1016/j.ygyno.2015.10.007</identifier><identifier>PMID: 26456138</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; Antimetabolites, Antineoplastic - administration &amp; dosage ; Antimetabolites, Antineoplastic - adverse effects ; Antineoplastic Agents, Phytogenic - administration &amp; dosage ; Antineoplastic Agents, Phytogenic - adverse effects ; Chemotherapy ; Chorionic Gonadotropin - blood ; Drug Administration Schedule ; Drug resistance ; Drug Resistance, Neoplasm ; Drug Substitution ; Etoposide - administration &amp; dosage ; Etoposide - adverse effects ; Female ; Hematology, Oncology and Palliative Medicine ; Humans ; Hydatidiform Mole - blood ; Hydatidiform Mole - drug therapy ; Hydatidiform Mole - secondary ; Low-risk gestational trophoblastic neoplasia ; Methotrexate - administration &amp; dosage ; Methotrexate - adverse effects ; Neoplasm Recurrence, Local - drug therapy ; Obstetrics and Gynecology ; Pregnancy ; Retrospective Studies ; Treatment Outcome ; Uterine Neoplasms - blood ; Uterine Neoplasms - drug therapy ; Uterine Neoplasms - pathology ; Young Adult</subject><ispartof>Gynecologic oncology, 2015-12, Vol.139 (3), p.429-432</ispartof><rights>Elsevier Inc.</rights><rights>2015 Elsevier Inc.</rights><rights>Copyright © 2015 Elsevier Inc. 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Methods Between 1980 and 2014, 166 consecutive patients with low-risk post-molar GTN were initially treated with a 5-day IM MTX or a 5-day DIV ETP regimen. The primary remission rates, changes in chemotherapy due to drug resistance or toxicity, and relapse rates were compared. Furthermore, we analyzed the factors that influenced the development of resistance to MTX. Results Primary remission rates were significantly higher among the ETP-treated patients than among the MTX-treated patients. Among the 42 patients who required a change in chemotherapy, 23 patients (22.6%) and 4 patients (6.3%) were diagnosed as being resistant to MTX and EPT, respectively. Maternal age and the presence of metastasis did not significantly influence the development of MTX resistance, although higher FIGO scores and pre-treatment human chorionic gonadotropin (hCG) levels of &gt; 5 × 104 mIU/mL were significantly more common among patients who developed MTX resistance. Moreover, a &lt; 30% decrease in hCG after the first cycles of MTX chemotherapy was significantly associated with the development of MTX resistance. Conclusions All patients with low-risk GTN eventually achieved complete remission, although several patients developed drug resistance to the first-line chemotherapy. A &lt; 30% decrease in hCG during the first chemotherapy cycle may be an early indicator of drug resistance after commencing a 5-day MTX regimen.</description><subject>Adult</subject><subject>Antimetabolites, Antineoplastic - administration &amp; dosage</subject><subject>Antimetabolites, Antineoplastic - adverse effects</subject><subject>Antineoplastic Agents, Phytogenic - administration &amp; dosage</subject><subject>Antineoplastic Agents, Phytogenic - adverse effects</subject><subject>Chemotherapy</subject><subject>Chorionic Gonadotropin - blood</subject><subject>Drug Administration Schedule</subject><subject>Drug resistance</subject><subject>Drug Resistance, Neoplasm</subject><subject>Drug Substitution</subject><subject>Etoposide - administration &amp; dosage</subject><subject>Etoposide - adverse effects</subject><subject>Female</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Humans</subject><subject>Hydatidiform Mole - blood</subject><subject>Hydatidiform Mole - drug therapy</subject><subject>Hydatidiform Mole - secondary</subject><subject>Low-risk gestational trophoblastic neoplasia</subject><subject>Methotrexate - administration &amp; dosage</subject><subject>Methotrexate - adverse effects</subject><subject>Neoplasm Recurrence, Local - drug therapy</subject><subject>Obstetrics and Gynecology</subject><subject>Pregnancy</subject><subject>Retrospective Studies</subject><subject>Treatment Outcome</subject><subject>Uterine Neoplasms - blood</subject><subject>Uterine Neoplasms - drug therapy</subject><subject>Uterine Neoplasms - pathology</subject><subject>Young Adult</subject><issn>0090-8258</issn><issn>1095-6859</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUk1v1DAQjRCILoVfgIR85JJlnMT5OICEVoVWKgKJReJmzTqTrbdOHGynVX4Y_w-nuyDEhZPt8Zs3M-9NkrzksObAyzeH9byfB7vOgIsYWQNUj5IVh0akZS2ax8kKoIG0zkR9ljzz_gAAOfDsaXKWlYUoeV6vkp8b24_otLcDsx0TaYsz-7T9znBoT6-L7RcWHGHoaQjMkZ9M8A__hM7MbHTUahWs8wtD66b9AtI-4KCIBfsXqR7YiEFHHs_udbhho_Uh7a1Bx4y9T2Mft2xPMTVoO6CJde14Y3cGfdCKDWTHeNX4PHnSofH04nSeJ98-XGw3l-n1549Xm_fXqSp4EVIqSfAiI6wRoN0V2AgFNZaIApQqSCBVrYKOt1RWVdXleZO1UdoGMCrcZPl58vrIOzr7Y4p9yV57RcZgbGXykldFU_KqFnmE5keoctZ7R50cne7RzZKDXPySB_ngl1z8WoLRr5j16lRg2vXU_sn5bVAEvD0CKI55p8lJr6J-KkruSAXZWv2fAu_-yVdGD1qhuaWZ_MFOLuocJ5E-kyC_LiuzbAwXcVVEWea_AAw6v6M</recordid><startdate>20151201</startdate><enddate>20151201</enddate><creator>Kizaki, Shoko</creator><creator>Hashimoto, Kazunori</creator><creator>Matsui, Hideo</creator><creator>Usui, Hirokazu</creator><creator>Shozu, Makio</creator><general>Elsevier Inc</general><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>7X8</scope><orcidid>https://orcid.org/0000-0002-6638-7389</orcidid></search><sort><creationdate>20151201</creationdate><title>Comparison of 5-day MTX and 5-day ETP treatment results and early predictors of drug resistance to 5-day MTX in patients with post-molar low-risk gestational trophoblastic neoplasia</title><author>Kizaki, Shoko ; Hashimoto, Kazunori ; Matsui, Hideo ; Usui, Hirokazu ; Shozu, Makio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c414t-e6e5142ea8a00db4a95c08a6aa50cc4e5ae7dc0f1de6777f3392d01690a101923</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Antimetabolites, Antineoplastic - administration &amp; dosage</topic><topic>Antimetabolites, Antineoplastic - adverse effects</topic><topic>Antineoplastic Agents, Phytogenic - administration &amp; dosage</topic><topic>Antineoplastic Agents, Phytogenic - adverse effects</topic><topic>Chemotherapy</topic><topic>Chorionic Gonadotropin - blood</topic><topic>Drug Administration Schedule</topic><topic>Drug resistance</topic><topic>Drug Resistance, Neoplasm</topic><topic>Drug Substitution</topic><topic>Etoposide - administration &amp; dosage</topic><topic>Etoposide - adverse effects</topic><topic>Female</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Humans</topic><topic>Hydatidiform Mole - blood</topic><topic>Hydatidiform Mole - drug therapy</topic><topic>Hydatidiform Mole - secondary</topic><topic>Low-risk gestational trophoblastic neoplasia</topic><topic>Methotrexate - administration &amp; dosage</topic><topic>Methotrexate - adverse effects</topic><topic>Neoplasm Recurrence, Local - drug therapy</topic><topic>Obstetrics and Gynecology</topic><topic>Pregnancy</topic><topic>Retrospective Studies</topic><topic>Treatment Outcome</topic><topic>Uterine Neoplasms - blood</topic><topic>Uterine Neoplasms - drug therapy</topic><topic>Uterine Neoplasms - pathology</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kizaki, Shoko</creatorcontrib><creatorcontrib>Hashimoto, Kazunori</creatorcontrib><creatorcontrib>Matsui, Hideo</creatorcontrib><creatorcontrib>Usui, Hirokazu</creatorcontrib><creatorcontrib>Shozu, Makio</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Gynecologic oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kizaki, Shoko</au><au>Hashimoto, Kazunori</au><au>Matsui, Hideo</au><au>Usui, Hirokazu</au><au>Shozu, Makio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparison of 5-day MTX and 5-day ETP treatment results and early predictors of drug resistance to 5-day MTX in patients with post-molar low-risk gestational trophoblastic neoplasia</atitle><jtitle>Gynecologic oncology</jtitle><addtitle>Gynecol Oncol</addtitle><date>2015-12-01</date><risdate>2015</risdate><volume>139</volume><issue>3</issue><spage>429</spage><epage>432</epage><pages>429-432</pages><issn>0090-8258</issn><eissn>1095-6859</eissn><abstract>Abstract Objective To determine the primary remission rates and predictors of drug resistance in patients with post-molar low-risk gestational trophoblastic neoplasia (GTN) who were treated with a 5-day intramuscular methotrexate (5-day IM MTX) or a 5-day drip infusion etoposide (5-day DIV ETP) regimen. Methods Between 1980 and 2014, 166 consecutive patients with low-risk post-molar GTN were initially treated with a 5-day IM MTX or a 5-day DIV ETP regimen. The primary remission rates, changes in chemotherapy due to drug resistance or toxicity, and relapse rates were compared. Furthermore, we analyzed the factors that influenced the development of resistance to MTX. Results Primary remission rates were significantly higher among the ETP-treated patients than among the MTX-treated patients. Among the 42 patients who required a change in chemotherapy, 23 patients (22.6%) and 4 patients (6.3%) were diagnosed as being resistant to MTX and EPT, respectively. Maternal age and the presence of metastasis did not significantly influence the development of MTX resistance, although higher FIGO scores and pre-treatment human chorionic gonadotropin (hCG) levels of &gt; 5 × 104 mIU/mL were significantly more common among patients who developed MTX resistance. Moreover, a &lt; 30% decrease in hCG after the first cycles of MTX chemotherapy was significantly associated with the development of MTX resistance. Conclusions All patients with low-risk GTN eventually achieved complete remission, although several patients developed drug resistance to the first-line chemotherapy. A &lt; 30% decrease in hCG during the first chemotherapy cycle may be an early indicator of drug resistance after commencing a 5-day MTX regimen.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26456138</pmid><doi>10.1016/j.ygyno.2015.10.007</doi><tpages>4</tpages><orcidid>https://orcid.org/0000-0002-6638-7389</orcidid></addata></record>
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subjects Adult
Antimetabolites, Antineoplastic - administration & dosage
Antimetabolites, Antineoplastic - adverse effects
Antineoplastic Agents, Phytogenic - administration & dosage
Antineoplastic Agents, Phytogenic - adverse effects
Chemotherapy
Chorionic Gonadotropin - blood
Drug Administration Schedule
Drug resistance
Drug Resistance, Neoplasm
Drug Substitution
Etoposide - administration & dosage
Etoposide - adverse effects
Female
Hematology, Oncology and Palliative Medicine
Humans
Hydatidiform Mole - blood
Hydatidiform Mole - drug therapy
Hydatidiform Mole - secondary
Low-risk gestational trophoblastic neoplasia
Methotrexate - administration & dosage
Methotrexate - adverse effects
Neoplasm Recurrence, Local - drug therapy
Obstetrics and Gynecology
Pregnancy
Retrospective Studies
Treatment Outcome
Uterine Neoplasms - blood
Uterine Neoplasms - drug therapy
Uterine Neoplasms - pathology
Young Adult
title Comparison of 5-day MTX and 5-day ETP treatment results and early predictors of drug resistance to 5-day MTX in patients with post-molar low-risk gestational trophoblastic neoplasia
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