Cargando…
Phase I study of neoadjuvant chemoradiotherapy with S-1 plus biweekly cisplatin for advanced gastric cancer patients with lymph node metastasis: -KOGC04-
BACKGROUND: In patients with highly advanced gastric cancer, the recurrence rate remains high and the prognosis disappointing. We previously reported a phase I study of a neoadjuvant chemoradiotherapy of S-1 plus weekly cisplatin. Although adequate safety and efficacy were reported, myelosuppression...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3904203/ https://www.ncbi.nlm.nih.gov/pubmed/24398302 http://dx.doi.org/10.1186/1748-717X-9-9 |
_version_ | 1782301198931460096 |
---|---|
author | Matsuda, Satoru Takahashi, Tsunehiro Fukada, Junichi Fukuda, Kazumasa Kawakubo, Hirofumi Saikawa, Yoshiro Kawaguchi, Osamu Takeuchi, Hiroya Shigematsu, Naoyuki Kitagawa, Yuko |
author_facet | Matsuda, Satoru Takahashi, Tsunehiro Fukada, Junichi Fukuda, Kazumasa Kawakubo, Hirofumi Saikawa, Yoshiro Kawaguchi, Osamu Takeuchi, Hiroya Shigematsu, Naoyuki Kitagawa, Yuko |
author_sort | Matsuda, Satoru |
collection | PubMed |
description | BACKGROUND: In patients with highly advanced gastric cancer, the recurrence rate remains high and the prognosis disappointing. We previously reported a phase I study of a neoadjuvant chemoradiotherapy of S-1 plus weekly cisplatin. Although adequate safety and efficacy were reported, myelosuppression was frequently observed, leading to treatment delay in several cases. To decrease toxicity and improve efficacy, we planned a phase I study with a modified chemotherapy regimen with biweekly cisplatin. METHODS: Patients with advanced gastric cancer and lymph node metastasis who were treated by our institution between 2011 and 2012 were eligible for inclusion. The initial chemoradiotherapy schedule consisted of 6 weeks of S-1 orally administered on days 1–15 with an escalating dose of cisplatin administered on days 1 and 15. The starting dose (level 1) of cisplatin was 15 mg/m(2), the second dose (level 2) was 20 mg/m(2), and the third dose (level 3) was 25 mg/m(2). Radiation of 40 Gy was administered in 20 fractions. After initial chemoradiotherapy, one cycle of combination chemotherapy with S-1 plus cisplatin was delivered. The second cycle was 42 days in duration and included S-1 administered on days 1–29 plus biweekly cisplatin administered on days 1, 15, and 29. After neoadjuvant treatment, a curative gastrectomy with extended (D2) lymph node dissection was planned. RESULTS: Nine patients were enrolled. At level 3, one patient had dose-limiting grade 3 diarrhea. Another patient experienced grade 3 nausea and intended to discontinue the treatment. Overall, because 2 of 3 patients experienced dose-limiting toxicity at level 3, we confirmed level 3 (Cisplatin 25 mg/m(2)) as the maximum tolerated dose and level 2 (Cisplatin 20 mg/m(2)) as the recommended dose (RD). The response rate was 78%, and 8 patients underwent curative gastrectomy. Resected specimens showed a histological response in 6 patients (75%), including one with a pathological complete response. CONCLUSIONS: In this phase I trial, RD of cisplatin was identified as 20 mg/m(2). Generally, S-1 plus biweekly cisplatin can be given safely with concurrent radiation. We have initiated a multicenter phase II trial to further confirm the efficacy and safety of this approach. TRIAL REGISTRATION: UMIN000008941 |
format | Online Article Text |
id | pubmed-3904203 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-39042032014-01-29 Phase I study of neoadjuvant chemoradiotherapy with S-1 plus biweekly cisplatin for advanced gastric cancer patients with lymph node metastasis: -KOGC04- Matsuda, Satoru Takahashi, Tsunehiro Fukada, Junichi Fukuda, Kazumasa Kawakubo, Hirofumi Saikawa, Yoshiro Kawaguchi, Osamu Takeuchi, Hiroya Shigematsu, Naoyuki Kitagawa, Yuko Radiat Oncol Research BACKGROUND: In patients with highly advanced gastric cancer, the recurrence rate remains high and the prognosis disappointing. We previously reported a phase I study of a neoadjuvant chemoradiotherapy of S-1 plus weekly cisplatin. Although adequate safety and efficacy were reported, myelosuppression was frequently observed, leading to treatment delay in several cases. To decrease toxicity and improve efficacy, we planned a phase I study with a modified chemotherapy regimen with biweekly cisplatin. METHODS: Patients with advanced gastric cancer and lymph node metastasis who were treated by our institution between 2011 and 2012 were eligible for inclusion. The initial chemoradiotherapy schedule consisted of 6 weeks of S-1 orally administered on days 1–15 with an escalating dose of cisplatin administered on days 1 and 15. The starting dose (level 1) of cisplatin was 15 mg/m(2), the second dose (level 2) was 20 mg/m(2), and the third dose (level 3) was 25 mg/m(2). Radiation of 40 Gy was administered in 20 fractions. After initial chemoradiotherapy, one cycle of combination chemotherapy with S-1 plus cisplatin was delivered. The second cycle was 42 days in duration and included S-1 administered on days 1–29 plus biweekly cisplatin administered on days 1, 15, and 29. After neoadjuvant treatment, a curative gastrectomy with extended (D2) lymph node dissection was planned. RESULTS: Nine patients were enrolled. At level 3, one patient had dose-limiting grade 3 diarrhea. Another patient experienced grade 3 nausea and intended to discontinue the treatment. Overall, because 2 of 3 patients experienced dose-limiting toxicity at level 3, we confirmed level 3 (Cisplatin 25 mg/m(2)) as the maximum tolerated dose and level 2 (Cisplatin 20 mg/m(2)) as the recommended dose (RD). The response rate was 78%, and 8 patients underwent curative gastrectomy. Resected specimens showed a histological response in 6 patients (75%), including one with a pathological complete response. CONCLUSIONS: In this phase I trial, RD of cisplatin was identified as 20 mg/m(2). Generally, S-1 plus biweekly cisplatin can be given safely with concurrent radiation. We have initiated a multicenter phase II trial to further confirm the efficacy and safety of this approach. TRIAL REGISTRATION: UMIN000008941 BioMed Central 2014-01-08 /pmc/articles/PMC3904203/ /pubmed/24398302 http://dx.doi.org/10.1186/1748-717X-9-9 Text en Copyright © 2014 Matsuda et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Matsuda, Satoru Takahashi, Tsunehiro Fukada, Junichi Fukuda, Kazumasa Kawakubo, Hirofumi Saikawa, Yoshiro Kawaguchi, Osamu Takeuchi, Hiroya Shigematsu, Naoyuki Kitagawa, Yuko Phase I study of neoadjuvant chemoradiotherapy with S-1 plus biweekly cisplatin for advanced gastric cancer patients with lymph node metastasis: -KOGC04- |
title | Phase I study of neoadjuvant chemoradiotherapy with S-1 plus biweekly cisplatin for advanced gastric cancer patients with lymph node metastasis: -KOGC04- |
title_full | Phase I study of neoadjuvant chemoradiotherapy with S-1 plus biweekly cisplatin for advanced gastric cancer patients with lymph node metastasis: -KOGC04- |
title_fullStr | Phase I study of neoadjuvant chemoradiotherapy with S-1 plus biweekly cisplatin for advanced gastric cancer patients with lymph node metastasis: -KOGC04- |
title_full_unstemmed | Phase I study of neoadjuvant chemoradiotherapy with S-1 plus biweekly cisplatin for advanced gastric cancer patients with lymph node metastasis: -KOGC04- |
title_short | Phase I study of neoadjuvant chemoradiotherapy with S-1 plus biweekly cisplatin for advanced gastric cancer patients with lymph node metastasis: -KOGC04- |
title_sort | phase i study of neoadjuvant chemoradiotherapy with s-1 plus biweekly cisplatin for advanced gastric cancer patients with lymph node metastasis: -kogc04- |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3904203/ https://www.ncbi.nlm.nih.gov/pubmed/24398302 http://dx.doi.org/10.1186/1748-717X-9-9 |
work_keys_str_mv | AT matsudasatoru phaseistudyofneoadjuvantchemoradiotherapywiths1plusbiweeklycisplatinforadvancedgastriccancerpatientswithlymphnodemetastasiskogc04 AT takahashitsunehiro phaseistudyofneoadjuvantchemoradiotherapywiths1plusbiweeklycisplatinforadvancedgastriccancerpatientswithlymphnodemetastasiskogc04 AT fukadajunichi phaseistudyofneoadjuvantchemoradiotherapywiths1plusbiweeklycisplatinforadvancedgastriccancerpatientswithlymphnodemetastasiskogc04 AT fukudakazumasa phaseistudyofneoadjuvantchemoradiotherapywiths1plusbiweeklycisplatinforadvancedgastriccancerpatientswithlymphnodemetastasiskogc04 AT kawakubohirofumi phaseistudyofneoadjuvantchemoradiotherapywiths1plusbiweeklycisplatinforadvancedgastriccancerpatientswithlymphnodemetastasiskogc04 AT saikawayoshiro phaseistudyofneoadjuvantchemoradiotherapywiths1plusbiweeklycisplatinforadvancedgastriccancerpatientswithlymphnodemetastasiskogc04 AT kawaguchiosamu phaseistudyofneoadjuvantchemoradiotherapywiths1plusbiweeklycisplatinforadvancedgastriccancerpatientswithlymphnodemetastasiskogc04 AT takeuchihiroya phaseistudyofneoadjuvantchemoradiotherapywiths1plusbiweeklycisplatinforadvancedgastriccancerpatientswithlymphnodemetastasiskogc04 AT shigematsunaoyuki phaseistudyofneoadjuvantchemoradiotherapywiths1plusbiweeklycisplatinforadvancedgastriccancerpatientswithlymphnodemetastasiskogc04 AT kitagawayuko phaseistudyofneoadjuvantchemoradiotherapywiths1plusbiweeklycisplatinforadvancedgastriccancerpatientswithlymphnodemetastasiskogc04 |