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Phase I Dose Escalation Study with Expansion Cohort of the Addition of Nab-Paclitaxel to Capecitabine and Oxaliplatin (CapOx) as First-Line Treatment of Metastatic Esophagogastric Adenocarcinoma (ACTION Study)
First-line triplet chemotherapy including a taxane may prolong survival in patients with metastatic esophagogastric cancer. The added toxicity of the taxane might be minimized by using nab-paclitaxel. The aim of this phase I study was to determine the feasibility of combining nab-paclitaxel with the...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627561/ https://www.ncbi.nlm.nih.gov/pubmed/31207904 http://dx.doi.org/10.3390/cancers11060827 |
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author | Schokker, Sandor van der Woude, Stephanie O. van Kleef, Jessy Joy van Zoen, Daan J. van Oijen, Martijn G. H. Mearadji, Banafsche Beenen, Ludo F. M. Stroes, Charlotte I. Waasdorp, Cynthia Jibodh, R. Aarti Creemers, Aafke Meijer, Sybren L. Hooijer, Gerrit K. J. Punt, Cornelis J. A. Bijlsma, Maarten F. van Laarhoven, Hanneke W. M. |
author_facet | Schokker, Sandor van der Woude, Stephanie O. van Kleef, Jessy Joy van Zoen, Daan J. van Oijen, Martijn G. H. Mearadji, Banafsche Beenen, Ludo F. M. Stroes, Charlotte I. Waasdorp, Cynthia Jibodh, R. Aarti Creemers, Aafke Meijer, Sybren L. Hooijer, Gerrit K. J. Punt, Cornelis J. A. Bijlsma, Maarten F. van Laarhoven, Hanneke W. M. |
author_sort | Schokker, Sandor |
collection | PubMed |
description | First-line triplet chemotherapy including a taxane may prolong survival in patients with metastatic esophagogastric cancer. The added toxicity of the taxane might be minimized by using nab-paclitaxel. The aim of this phase I study was to determine the feasibility of combining nab-paclitaxel with the standard of care in the Netherlands, capecitabine and oxaliplatin (CapOx). Patients with metastatic esophagogastric adenocarcinoma received oxaliplatin 65 mg/m(2) on days 1 and 8, and capecitabine 1000 mg/m(2) bid on days 1–14 in a 21-day cycle, with nab-paclitaxel on days 1 and 8 at four dose levels (60, 80, 100, and 120 mg/m(2), respectively), using a standard 3 + 3 dose escalation phase, followed by a safety expansion cohort. Baseline tissue and serum markers for activated tumor stroma were assessed as biomarkers for response and survival. Twenty-six patients were included. The first two dose-limiting toxicities (i.e., diarrhea and dehydration) occurred at dose level 3. The resulting maximum tolerable dose (MTD) of 80 mg/m(2) was used in the expansion cohort, but was reduced to 60 mg/m(2) after three out of eight patients experienced diarrhea grade 3. The objective response rate was 54%. The median progression-free (PFS) and overall survival were 8.0 and 12.8 months, respectively. High baseline serum ADAM12 was associated with a significantly shorter PFS (p = 0.011). In conclusion, albeit that the addition of nab-paclitaxel 60 mg/m(2) to CapOx may be better tolerated than other taxane triplets, relevant toxicity was observed. There is a rationale for preserving taxanes for later-line treatment. ADAM12 is a potential biomarker to predict survival, and warrants further investigation. |
format | Online Article Text |
id | pubmed-6627561 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-66275612019-07-23 Phase I Dose Escalation Study with Expansion Cohort of the Addition of Nab-Paclitaxel to Capecitabine and Oxaliplatin (CapOx) as First-Line Treatment of Metastatic Esophagogastric Adenocarcinoma (ACTION Study) Schokker, Sandor van der Woude, Stephanie O. van Kleef, Jessy Joy van Zoen, Daan J. van Oijen, Martijn G. H. Mearadji, Banafsche Beenen, Ludo F. M. Stroes, Charlotte I. Waasdorp, Cynthia Jibodh, R. Aarti Creemers, Aafke Meijer, Sybren L. Hooijer, Gerrit K. J. Punt, Cornelis J. A. Bijlsma, Maarten F. van Laarhoven, Hanneke W. M. Cancers (Basel) Article First-line triplet chemotherapy including a taxane may prolong survival in patients with metastatic esophagogastric cancer. The added toxicity of the taxane might be minimized by using nab-paclitaxel. The aim of this phase I study was to determine the feasibility of combining nab-paclitaxel with the standard of care in the Netherlands, capecitabine and oxaliplatin (CapOx). Patients with metastatic esophagogastric adenocarcinoma received oxaliplatin 65 mg/m(2) on days 1 and 8, and capecitabine 1000 mg/m(2) bid on days 1–14 in a 21-day cycle, with nab-paclitaxel on days 1 and 8 at four dose levels (60, 80, 100, and 120 mg/m(2), respectively), using a standard 3 + 3 dose escalation phase, followed by a safety expansion cohort. Baseline tissue and serum markers for activated tumor stroma were assessed as biomarkers for response and survival. Twenty-six patients were included. The first two dose-limiting toxicities (i.e., diarrhea and dehydration) occurred at dose level 3. The resulting maximum tolerable dose (MTD) of 80 mg/m(2) was used in the expansion cohort, but was reduced to 60 mg/m(2) after three out of eight patients experienced diarrhea grade 3. The objective response rate was 54%. The median progression-free (PFS) and overall survival were 8.0 and 12.8 months, respectively. High baseline serum ADAM12 was associated with a significantly shorter PFS (p = 0.011). In conclusion, albeit that the addition of nab-paclitaxel 60 mg/m(2) to CapOx may be better tolerated than other taxane triplets, relevant toxicity was observed. There is a rationale for preserving taxanes for later-line treatment. ADAM12 is a potential biomarker to predict survival, and warrants further investigation. MDPI 2019-06-14 /pmc/articles/PMC6627561/ /pubmed/31207904 http://dx.doi.org/10.3390/cancers11060827 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Schokker, Sandor van der Woude, Stephanie O. van Kleef, Jessy Joy van Zoen, Daan J. van Oijen, Martijn G. H. Mearadji, Banafsche Beenen, Ludo F. M. Stroes, Charlotte I. Waasdorp, Cynthia Jibodh, R. Aarti Creemers, Aafke Meijer, Sybren L. Hooijer, Gerrit K. J. Punt, Cornelis J. A. Bijlsma, Maarten F. van Laarhoven, Hanneke W. M. Phase I Dose Escalation Study with Expansion Cohort of the Addition of Nab-Paclitaxel to Capecitabine and Oxaliplatin (CapOx) as First-Line Treatment of Metastatic Esophagogastric Adenocarcinoma (ACTION Study) |
title | Phase I Dose Escalation Study with Expansion Cohort of the Addition of Nab-Paclitaxel to Capecitabine and Oxaliplatin (CapOx) as First-Line Treatment of Metastatic Esophagogastric Adenocarcinoma (ACTION Study) |
title_full | Phase I Dose Escalation Study with Expansion Cohort of the Addition of Nab-Paclitaxel to Capecitabine and Oxaliplatin (CapOx) as First-Line Treatment of Metastatic Esophagogastric Adenocarcinoma (ACTION Study) |
title_fullStr | Phase I Dose Escalation Study with Expansion Cohort of the Addition of Nab-Paclitaxel to Capecitabine and Oxaliplatin (CapOx) as First-Line Treatment of Metastatic Esophagogastric Adenocarcinoma (ACTION Study) |
title_full_unstemmed | Phase I Dose Escalation Study with Expansion Cohort of the Addition of Nab-Paclitaxel to Capecitabine and Oxaliplatin (CapOx) as First-Line Treatment of Metastatic Esophagogastric Adenocarcinoma (ACTION Study) |
title_short | Phase I Dose Escalation Study with Expansion Cohort of the Addition of Nab-Paclitaxel to Capecitabine and Oxaliplatin (CapOx) as First-Line Treatment of Metastatic Esophagogastric Adenocarcinoma (ACTION Study) |
title_sort | phase i dose escalation study with expansion cohort of the addition of nab-paclitaxel to capecitabine and oxaliplatin (capox) as first-line treatment of metastatic esophagogastric adenocarcinoma (action study) |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627561/ https://www.ncbi.nlm.nih.gov/pubmed/31207904 http://dx.doi.org/10.3390/cancers11060827 |
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