Phase I Study Evaluating the Combination of Afatinib with Carboplatin and Pemetrexed After First-line EGFR-TKIs
Promising reports have described the combination of first-generation epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKIs) with carboplatin plus pemetrexed or bevacizumab. However, no analysis of afatinib with platinum-doublet chemotherapies has been performed. We evaluated the saf...
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| Veröffentlicht in: | Anticancer research 2018-08, Vol.38 (8), p.4699-4704 |
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| creator | Watanabe, Satoshi Yamaguchi, O U Masumoto, A I Maeno, Yuri Kawashima, Yosuke Ishimoto, Osamu Sugawara, Shunichi Yoshizawa, Hirohisa Kikuchi, Toshiaki Nukiwa, Toshihiro Kobayashi, Kunihiko |
| description | Promising reports have described the combination of first-generation epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKIs) with carboplatin plus pemetrexed or bevacizumab. However, no analysis of afatinib with platinum-doublet chemotherapies has been performed.
We evaluated the safety and antitumor efficacy of afatinib combined with carboplatin and pemetrexed in EGFR-mutated non-small-cell lung cancer (NSCLC) patients who progressed during first-generation EGFR-TKIs.
Ten patients received 20 or 30 mg/day afatinib with carboplatin (area under the curve, 5) and pemetrexed (500 mg/m
). Dose-limiting toxicities included delay of afatinib ≥14 days, grade 3 diarrhea, grade 3 hypokalemia, grade 3 serum amylase increase and grade 4 thrombocytopenia. The recommended dose of afatinib was 20 mg/day in this combination therapy. Overall response rate was 30% and median progression-free survival was 13.7 months.
This is the first study to investigate the combination of afatinib, carboplatin and pemetrexed. At the recommended dose, this combination was well tolerated and had a good clinical efficacy. |
| doi_str_mv | 10.21873/anticanres.12776 |
| format | Article |
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We evaluated the safety and antitumor efficacy of afatinib combined with carboplatin and pemetrexed in EGFR-mutated non-small-cell lung cancer (NSCLC) patients who progressed during first-generation EGFR-TKIs.
Ten patients received 20 or 30 mg/day afatinib with carboplatin (area under the curve, 5) and pemetrexed (500 mg/m
). Dose-limiting toxicities included delay of afatinib ≥14 days, grade 3 diarrhea, grade 3 hypokalemia, grade 3 serum amylase increase and grade 4 thrombocytopenia. The recommended dose of afatinib was 20 mg/day in this combination therapy. Overall response rate was 30% and median progression-free survival was 13.7 months.
This is the first study to investigate the combination of afatinib, carboplatin and pemetrexed. At the recommended dose, this combination was well tolerated and had a good clinical efficacy.</description><identifier>ISSN: 0250-7005</identifier><identifier>EISSN: 1791-7530</identifier><identifier>DOI: 10.21873/anticanres.12776</identifier><identifier>PMID: 30061238</identifier><language>eng</language><publisher>Greece: International Institute of Anticancer Research</publisher><subject>Adult ; Aged ; Anticancer properties ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Antitumor activity ; Bevacizumab ; Bevacizumab - therapeutic use ; Carboplatin ; Carboplatin - administration & dosage ; Carcinoma, Non-Small-Cell Lung - drug therapy ; Carcinoma, Non-Small-Cell Lung - genetics ; Diarrhea ; Disease-Free Survival ; Epidermal growth factor ; Epidermal growth factor receptors ; Female ; Growth factors ; Humans ; Hypokalemia ; Lung cancer ; Lung Neoplasms - drug therapy ; Lung Neoplasms - genetics ; Male ; Middle Aged ; Monoclonal antibodies ; Mutation - genetics ; Non-small cell lung carcinoma ; Organoplatinum Compounds - therapeutic use ; Patients ; Pemetrexed - administration & dosage ; Platinum ; Protein Kinase Inhibitors - therapeutic use ; Quinazolines - administration & dosage ; Receptor, Epidermal Growth Factor - metabolism ; Targeted cancer therapy ; Thrombocytopenia ; Toxicity ; Treatment Outcome ; Tyrosine ; Young Adult</subject><ispartof>Anticancer research, 2018-08, Vol.38 (8), p.4699-4704</ispartof><rights>Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.</rights><rights>Copyright International Institute of Anticancer Research Aug 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-3cb1c05fede3eda15909e5f9b1a0246339c0de8d461b7a2a6651cd3be6ce0ee33</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30061238$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Watanabe, Satoshi</creatorcontrib><creatorcontrib>Yamaguchi, O U</creatorcontrib><creatorcontrib>Masumoto, A I</creatorcontrib><creatorcontrib>Maeno, Yuri</creatorcontrib><creatorcontrib>Kawashima, Yosuke</creatorcontrib><creatorcontrib>Ishimoto, Osamu</creatorcontrib><creatorcontrib>Sugawara, Shunichi</creatorcontrib><creatorcontrib>Yoshizawa, Hirohisa</creatorcontrib><creatorcontrib>Kikuchi, Toshiaki</creatorcontrib><creatorcontrib>Nukiwa, Toshihiro</creatorcontrib><creatorcontrib>Kobayashi, Kunihiko</creatorcontrib><title>Phase I Study Evaluating the Combination of Afatinib with Carboplatin and Pemetrexed After First-line EGFR-TKIs</title><title>Anticancer research</title><addtitle>Anticancer Res</addtitle><description>Promising reports have described the combination of first-generation epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKIs) with carboplatin plus pemetrexed or bevacizumab. However, no analysis of afatinib with platinum-doublet chemotherapies has been performed.
We evaluated the safety and antitumor efficacy of afatinib combined with carboplatin and pemetrexed in EGFR-mutated non-small-cell lung cancer (NSCLC) patients who progressed during first-generation EGFR-TKIs.
Ten patients received 20 or 30 mg/day afatinib with carboplatin (area under the curve, 5) and pemetrexed (500 mg/m
). Dose-limiting toxicities included delay of afatinib ≥14 days, grade 3 diarrhea, grade 3 hypokalemia, grade 3 serum amylase increase and grade 4 thrombocytopenia. The recommended dose of afatinib was 20 mg/day in this combination therapy. Overall response rate was 30% and median progression-free survival was 13.7 months.
This is the first study to investigate the combination of afatinib, carboplatin and pemetrexed. At the recommended dose, this combination was well tolerated and had a good clinical efficacy.</description><subject>Adult</subject><subject>Aged</subject><subject>Anticancer properties</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Antitumor activity</subject><subject>Bevacizumab</subject><subject>Bevacizumab - therapeutic use</subject><subject>Carboplatin</subject><subject>Carboplatin - administration & dosage</subject><subject>Carcinoma, Non-Small-Cell Lung - drug therapy</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Diarrhea</subject><subject>Disease-Free Survival</subject><subject>Epidermal growth factor</subject><subject>Epidermal growth factor receptors</subject><subject>Female</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Hypokalemia</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Lung Neoplasms - genetics</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Monoclonal antibodies</subject><subject>Mutation - genetics</subject><subject>Non-small cell lung carcinoma</subject><subject>Organoplatinum Compounds - therapeutic use</subject><subject>Patients</subject><subject>Pemetrexed - administration & dosage</subject><subject>Platinum</subject><subject>Protein Kinase Inhibitors - therapeutic use</subject><subject>Quinazolines - administration & dosage</subject><subject>Receptor, Epidermal Growth Factor - metabolism</subject><subject>Targeted cancer therapy</subject><subject>Thrombocytopenia</subject><subject>Toxicity</subject><subject>Treatment Outcome</subject><subject>Tyrosine</subject><subject>Young Adult</subject><issn>0250-7005</issn><issn>1791-7530</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkEtPwkAUhSdGI4j-ADdmEtfFedBOuyQNIJFEorhupjO3UtJOcWaq8u8tD3V1X-ecm3wI3VIyZDQW_EEaXyppLLghZUJEZ6hPRUIDEXJyjvqEhSQQhIQ9dOXchpAoSmJ-iXq8aynjcR81y7V0gOf41bd6hyefsmqlL8079mvAaVPnpenmxuCmwONifypz_FX6NU6lzZtttV9haTReQg3ewjfoTujB4mlpnQ-q0gCezKYvwepp7q7RRSErBzenOkBv08kqfQwWz7N5Ol4EigvmA65yqkhYgAYOWtIwIQmERZJTSdgo4jxRREOsRxHNhWQyikKqNM8hUkAAOB-g-2Pu1jYfLTifbZrWmu5lxigXo7CLiTsVPaqUbZyzUGRbW9bS7jJKsgPi7B9xdkDcee5OyW1eg_5z_DLlPzu2emY</recordid><startdate>201808</startdate><enddate>201808</enddate><creator>Watanabe, Satoshi</creator><creator>Yamaguchi, O U</creator><creator>Masumoto, A I</creator><creator>Maeno, Yuri</creator><creator>Kawashima, Yosuke</creator><creator>Ishimoto, Osamu</creator><creator>Sugawara, Shunichi</creator><creator>Yoshizawa, Hirohisa</creator><creator>Kikuchi, Toshiaki</creator><creator>Nukiwa, Toshihiro</creator><creator>Kobayashi, Kunihiko</creator><general>International Institute of Anticancer Research</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>7QO</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>201808</creationdate><title>Phase I Study Evaluating the Combination of Afatinib with Carboplatin and Pemetrexed After First-line EGFR-TKIs</title><author>Watanabe, Satoshi ; Yamaguchi, O U ; Masumoto, A I ; Maeno, Yuri ; Kawashima, Yosuke ; Ishimoto, Osamu ; Sugawara, Shunichi ; Yoshizawa, Hirohisa ; Kikuchi, Toshiaki ; Nukiwa, Toshihiro ; Kobayashi, Kunihiko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c372t-3cb1c05fede3eda15909e5f9b1a0246339c0de8d461b7a2a6651cd3be6ce0ee33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Anticancer properties</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Antitumor activity</topic><topic>Bevacizumab</topic><topic>Bevacizumab - therapeutic use</topic><topic>Carboplatin</topic><topic>Carboplatin - administration & dosage</topic><topic>Carcinoma, Non-Small-Cell Lung - drug therapy</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Diarrhea</topic><topic>Disease-Free Survival</topic><topic>Epidermal growth factor</topic><topic>Epidermal growth factor receptors</topic><topic>Female</topic><topic>Growth factors</topic><topic>Humans</topic><topic>Hypokalemia</topic><topic>Lung cancer</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Lung Neoplasms - genetics</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Monoclonal antibodies</topic><topic>Mutation - genetics</topic><topic>Non-small cell lung carcinoma</topic><topic>Organoplatinum Compounds - therapeutic use</topic><topic>Patients</topic><topic>Pemetrexed - administration & dosage</topic><topic>Platinum</topic><topic>Protein Kinase Inhibitors - therapeutic use</topic><topic>Quinazolines - administration & dosage</topic><topic>Receptor, Epidermal Growth Factor - metabolism</topic><topic>Targeted cancer therapy</topic><topic>Thrombocytopenia</topic><topic>Toxicity</topic><topic>Treatment Outcome</topic><topic>Tyrosine</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Watanabe, Satoshi</creatorcontrib><creatorcontrib>Yamaguchi, O U</creatorcontrib><creatorcontrib>Masumoto, A I</creatorcontrib><creatorcontrib>Maeno, Yuri</creatorcontrib><creatorcontrib>Kawashima, Yosuke</creatorcontrib><creatorcontrib>Ishimoto, Osamu</creatorcontrib><creatorcontrib>Sugawara, Shunichi</creatorcontrib><creatorcontrib>Yoshizawa, Hirohisa</creatorcontrib><creatorcontrib>Kikuchi, Toshiaki</creatorcontrib><creatorcontrib>Nukiwa, Toshihiro</creatorcontrib><creatorcontrib>Kobayashi, Kunihiko</creatorcontrib><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>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS 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>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Anticancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Watanabe, Satoshi</au><au>Yamaguchi, O U</au><au>Masumoto, A I</au><au>Maeno, Yuri</au><au>Kawashima, Yosuke</au><au>Ishimoto, Osamu</au><au>Sugawara, Shunichi</au><au>Yoshizawa, Hirohisa</au><au>Kikuchi, Toshiaki</au><au>Nukiwa, Toshihiro</au><au>Kobayashi, Kunihiko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phase I Study Evaluating the Combination of Afatinib with Carboplatin and Pemetrexed After First-line EGFR-TKIs</atitle><jtitle>Anticancer research</jtitle><addtitle>Anticancer Res</addtitle><date>2018-08</date><risdate>2018</risdate><volume>38</volume><issue>8</issue><spage>4699</spage><epage>4704</epage><pages>4699-4704</pages><issn>0250-7005</issn><eissn>1791-7530</eissn><abstract>Promising reports have described the combination of first-generation epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKIs) with carboplatin plus pemetrexed or bevacizumab. However, no analysis of afatinib with platinum-doublet chemotherapies has been performed.
We evaluated the safety and antitumor efficacy of afatinib combined with carboplatin and pemetrexed in EGFR-mutated non-small-cell lung cancer (NSCLC) patients who progressed during first-generation EGFR-TKIs.
Ten patients received 20 or 30 mg/day afatinib with carboplatin (area under the curve, 5) and pemetrexed (500 mg/m
). Dose-limiting toxicities included delay of afatinib ≥14 days, grade 3 diarrhea, grade 3 hypokalemia, grade 3 serum amylase increase and grade 4 thrombocytopenia. The recommended dose of afatinib was 20 mg/day in this combination therapy. Overall response rate was 30% and median progression-free survival was 13.7 months.
This is the first study to investigate the combination of afatinib, carboplatin and pemetrexed. At the recommended dose, this combination was well tolerated and had a good clinical efficacy.</abstract><cop>Greece</cop><pub>International Institute of Anticancer Research</pub><pmid>30061238</pmid><doi>10.21873/anticanres.12776</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Anticancer research, 2018-08, Vol.38 (8), p.4699-4704 |
| issn | 0250-7005 1791-7530 |
| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals |
| subjects | Adult Aged Anticancer properties Antineoplastic Combined Chemotherapy Protocols - therapeutic use Antitumor activity Bevacizumab Bevacizumab - therapeutic use Carboplatin Carboplatin - administration & dosage Carcinoma, Non-Small-Cell Lung - drug therapy Carcinoma, Non-Small-Cell Lung - genetics Diarrhea Disease-Free Survival Epidermal growth factor Epidermal growth factor receptors Female Growth factors Humans Hypokalemia Lung cancer Lung Neoplasms - drug therapy Lung Neoplasms - genetics Male Middle Aged Monoclonal antibodies Mutation - genetics Non-small cell lung carcinoma Organoplatinum Compounds - therapeutic use Patients Pemetrexed - administration & dosage Platinum Protein Kinase Inhibitors - therapeutic use Quinazolines - administration & dosage Receptor, Epidermal Growth Factor - metabolism Targeted cancer therapy Thrombocytopenia Toxicity Treatment Outcome Tyrosine Young Adult |
| title | Phase I Study Evaluating the Combination of Afatinib with Carboplatin and Pemetrexed After First-line EGFR-TKIs |
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