Cargando…
Phase I dose escalation study of sorafenib plus S-1 for advanced solid tumors
S-1, an oral pyrimidine fluoride-derived agent, is effective against various cancers. Sorafenib, an oral multikinase inhibitor, was found to prolong the survival of various cancers and enhance the cytotoxicity of chemotherapeutic agents. We conducted a phase I dose escalation study to determine dose...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921110/ https://www.ncbi.nlm.nih.gov/pubmed/33649501 http://dx.doi.org/10.1038/s41598-021-84279-6 |
_version_ | 1783658409996845056 |
---|---|
author | Tsai, Hui-Jen Shiah, Her-Shyong Chang, Jang-Yang Su, Wu-Chou Chiang, Nai-Jung Chen, Li-Tzong |
author_facet | Tsai, Hui-Jen Shiah, Her-Shyong Chang, Jang-Yang Su, Wu-Chou Chiang, Nai-Jung Chen, Li-Tzong |
author_sort | Tsai, Hui-Jen |
collection | PubMed |
description | S-1, an oral pyrimidine fluoride-derived agent, is effective against various cancers. Sorafenib, an oral multikinase inhibitor, was found to prolong the survival of various cancers and enhance the cytotoxicity of chemotherapeutic agents. We conducted a phase I dose escalation study to determine dose-limiting toxicity (DLT) and maximal tolerated dose (MTD) of S-1 when combined with sorafenib for refractory solid tumors. Eligible patients received escalating doses (30, 35, and 40 mg/m(2) bid) of S-1 Day 1 (D1)–D14 and continuous sorafenib 400 mg bid from cycle 1 D8 every 21 days in a standard 3 + 3 study design. Primary endpoint was MTD. Thirteen patients were enrolled between May 2010 and Feb 2012. DLT developed in two (one grade 3 erythema and one prolonged grade 2 hand-foot-skin reaction) of the 6 patients at 35 mg/m(2) dose level. One pancreatic neuroendocrine tumor (pNET) patient achieved a durable partial response (27.9 months). Four colon cancer patients had stable disease and 3 of them had progression-free survival greater than 6 months. This study determined the recommended (MTD) S-1 dose of 30 mg/m(2) bid for this regimen. This result warrants further phase II studies for advanced pNET and colon cancer to evaluate the efficacy of this combination. |
format | Online Article Text |
id | pubmed-7921110 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-79211102021-03-02 Phase I dose escalation study of sorafenib plus S-1 for advanced solid tumors Tsai, Hui-Jen Shiah, Her-Shyong Chang, Jang-Yang Su, Wu-Chou Chiang, Nai-Jung Chen, Li-Tzong Sci Rep Article S-1, an oral pyrimidine fluoride-derived agent, is effective against various cancers. Sorafenib, an oral multikinase inhibitor, was found to prolong the survival of various cancers and enhance the cytotoxicity of chemotherapeutic agents. We conducted a phase I dose escalation study to determine dose-limiting toxicity (DLT) and maximal tolerated dose (MTD) of S-1 when combined with sorafenib for refractory solid tumors. Eligible patients received escalating doses (30, 35, and 40 mg/m(2) bid) of S-1 Day 1 (D1)–D14 and continuous sorafenib 400 mg bid from cycle 1 D8 every 21 days in a standard 3 + 3 study design. Primary endpoint was MTD. Thirteen patients were enrolled between May 2010 and Feb 2012. DLT developed in two (one grade 3 erythema and one prolonged grade 2 hand-foot-skin reaction) of the 6 patients at 35 mg/m(2) dose level. One pancreatic neuroendocrine tumor (pNET) patient achieved a durable partial response (27.9 months). Four colon cancer patients had stable disease and 3 of them had progression-free survival greater than 6 months. This study determined the recommended (MTD) S-1 dose of 30 mg/m(2) bid for this regimen. This result warrants further phase II studies for advanced pNET and colon cancer to evaluate the efficacy of this combination. Nature Publishing Group UK 2021-03-01 /pmc/articles/PMC7921110/ /pubmed/33649501 http://dx.doi.org/10.1038/s41598-021-84279-6 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Tsai, Hui-Jen Shiah, Her-Shyong Chang, Jang-Yang Su, Wu-Chou Chiang, Nai-Jung Chen, Li-Tzong Phase I dose escalation study of sorafenib plus S-1 for advanced solid tumors |
title | Phase I dose escalation study of sorafenib plus S-1 for advanced solid tumors |
title_full | Phase I dose escalation study of sorafenib plus S-1 for advanced solid tumors |
title_fullStr | Phase I dose escalation study of sorafenib plus S-1 for advanced solid tumors |
title_full_unstemmed | Phase I dose escalation study of sorafenib plus S-1 for advanced solid tumors |
title_short | Phase I dose escalation study of sorafenib plus S-1 for advanced solid tumors |
title_sort | phase i dose escalation study of sorafenib plus s-1 for advanced solid tumors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921110/ https://www.ncbi.nlm.nih.gov/pubmed/33649501 http://dx.doi.org/10.1038/s41598-021-84279-6 |
work_keys_str_mv | AT tsaihuijen phaseidoseescalationstudyofsorafenibpluss1foradvancedsolidtumors AT shiahhershyong phaseidoseescalationstudyofsorafenibpluss1foradvancedsolidtumors AT changjangyang phaseidoseescalationstudyofsorafenibpluss1foradvancedsolidtumors AT suwuchou phaseidoseescalationstudyofsorafenibpluss1foradvancedsolidtumors AT chiangnaijung phaseidoseescalationstudyofsorafenibpluss1foradvancedsolidtumors AT chenlitzong phaseidoseescalationstudyofsorafenibpluss1foradvancedsolidtumors |