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A phase I/II study of GLIF combination chemotherapy for taxane/platinum-refractory/resistant endometrial cancer (GOGO-EM2)
PURPOSE: Development of new treatment strategies for endometrial cancer that has become refractory or resistant to taxane/platinum is a critical need. The present study was a phase I/II study of gemcitabine, levofolinate, irinotecan, and 5-fluorouracil (5-FU) (GLIF) combination chemotherapy to deter...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6132850/ https://www.ncbi.nlm.nih.gov/pubmed/30030584 http://dx.doi.org/10.1007/s00280-018-3648-y |
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author | Tanaka, Yusuke Ueda, Yutaka Nakagawa, Satoshi Matsuzaki, Shinya Kobayashi, Eiji Shiki, Yasuhiko Nishio, Yukihiro Takemura, Masahiko Yamamoto, Toshiya Sawada, Kenjiro Tomimatsu, Takuji Yoshino, Kiyoshi Kimura, Tadashi |
author_facet | Tanaka, Yusuke Ueda, Yutaka Nakagawa, Satoshi Matsuzaki, Shinya Kobayashi, Eiji Shiki, Yasuhiko Nishio, Yukihiro Takemura, Masahiko Yamamoto, Toshiya Sawada, Kenjiro Tomimatsu, Takuji Yoshino, Kiyoshi Kimura, Tadashi |
author_sort | Tanaka, Yusuke |
collection | PubMed |
description | PURPOSE: Development of new treatment strategies for endometrial cancer that has become refractory or resistant to taxane/platinum is a critical need. The present study was a phase I/II study of gemcitabine, levofolinate, irinotecan, and 5-fluorouracil (5-FU) (GLIF) combination chemotherapy to determine optimal dosages, safety, and efficacy. METHODS: Taxane/platinum-resistant or -refractory endometrial disease was defined as tumor progression within 6 months after a taxane/platinum-based regimen. Maximum tolerated dose was investigated by a 3 + 3-designed phase I study. The phase II study was conducted using the recommended doses determined in the phase I study. RESULTS: The dosages recommended for the phase II trial were determined, in the phase I trial, to be: gemcitabine 800 mg/m(2), levofolinate 100 mg/m(2), irinotecan 80 mg/m(2), and 5-FU 1000 mg/m(2). Thirty patients were enrolled, including the three patients who received GLIF therapy at the same dose as the recommended phase II dose in the phase I study. Two patients were excluded at this point due to study protocol violations, and the remaining 28 patients were included for analysis. Phase II revealed that the response and disease control rates were 7.1% (2/28) and 39.3% (11/28), respectively, and that the median PFS and OS were 3 months [95% confidence interval (CI) 3–7] and 12 months (95% CI 9–17), respectively. Febrile or grade 4 neutropenia was observed in 14% (4/28) of the cases. Grade 3 or 4 thrombocytopenia was not observed. CONCLUSION: We found that GLIF combination chemotherapy is potentially a useful treatment option for endometrial cancers refractory or resistant to taxane/platinum-based chemotherapy. |
format | Online Article Text |
id | pubmed-6132850 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-61328502018-09-13 A phase I/II study of GLIF combination chemotherapy for taxane/platinum-refractory/resistant endometrial cancer (GOGO-EM2) Tanaka, Yusuke Ueda, Yutaka Nakagawa, Satoshi Matsuzaki, Shinya Kobayashi, Eiji Shiki, Yasuhiko Nishio, Yukihiro Takemura, Masahiko Yamamoto, Toshiya Sawada, Kenjiro Tomimatsu, Takuji Yoshino, Kiyoshi Kimura, Tadashi Cancer Chemother Pharmacol Original Article PURPOSE: Development of new treatment strategies for endometrial cancer that has become refractory or resistant to taxane/platinum is a critical need. The present study was a phase I/II study of gemcitabine, levofolinate, irinotecan, and 5-fluorouracil (5-FU) (GLIF) combination chemotherapy to determine optimal dosages, safety, and efficacy. METHODS: Taxane/platinum-resistant or -refractory endometrial disease was defined as tumor progression within 6 months after a taxane/platinum-based regimen. Maximum tolerated dose was investigated by a 3 + 3-designed phase I study. The phase II study was conducted using the recommended doses determined in the phase I study. RESULTS: The dosages recommended for the phase II trial were determined, in the phase I trial, to be: gemcitabine 800 mg/m(2), levofolinate 100 mg/m(2), irinotecan 80 mg/m(2), and 5-FU 1000 mg/m(2). Thirty patients were enrolled, including the three patients who received GLIF therapy at the same dose as the recommended phase II dose in the phase I study. Two patients were excluded at this point due to study protocol violations, and the remaining 28 patients were included for analysis. Phase II revealed that the response and disease control rates were 7.1% (2/28) and 39.3% (11/28), respectively, and that the median PFS and OS were 3 months [95% confidence interval (CI) 3–7] and 12 months (95% CI 9–17), respectively. Febrile or grade 4 neutropenia was observed in 14% (4/28) of the cases. Grade 3 or 4 thrombocytopenia was not observed. CONCLUSION: We found that GLIF combination chemotherapy is potentially a useful treatment option for endometrial cancers refractory or resistant to taxane/platinum-based chemotherapy. Springer Berlin Heidelberg 2018-07-20 2018 /pmc/articles/PMC6132850/ /pubmed/30030584 http://dx.doi.org/10.1007/s00280-018-3648-y Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Original Article Tanaka, Yusuke Ueda, Yutaka Nakagawa, Satoshi Matsuzaki, Shinya Kobayashi, Eiji Shiki, Yasuhiko Nishio, Yukihiro Takemura, Masahiko Yamamoto, Toshiya Sawada, Kenjiro Tomimatsu, Takuji Yoshino, Kiyoshi Kimura, Tadashi A phase I/II study of GLIF combination chemotherapy for taxane/platinum-refractory/resistant endometrial cancer (GOGO-EM2) |
title | A phase I/II study of GLIF combination chemotherapy for taxane/platinum-refractory/resistant endometrial cancer (GOGO-EM2) |
title_full | A phase I/II study of GLIF combination chemotherapy for taxane/platinum-refractory/resistant endometrial cancer (GOGO-EM2) |
title_fullStr | A phase I/II study of GLIF combination chemotherapy for taxane/platinum-refractory/resistant endometrial cancer (GOGO-EM2) |
title_full_unstemmed | A phase I/II study of GLIF combination chemotherapy for taxane/platinum-refractory/resistant endometrial cancer (GOGO-EM2) |
title_short | A phase I/II study of GLIF combination chemotherapy for taxane/platinum-refractory/resistant endometrial cancer (GOGO-EM2) |
title_sort | phase i/ii study of glif combination chemotherapy for taxane/platinum-refractory/resistant endometrial cancer (gogo-em2) |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6132850/ https://www.ncbi.nlm.nih.gov/pubmed/30030584 http://dx.doi.org/10.1007/s00280-018-3648-y |
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