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 standard of care in the Netherlands, capecitabine and oxaliplatin (CapOx). Patients with metastatic esophagogastric adenocarcinoma received oxaliplatin 65 mg/m2 on days 1 and 8, and capecitabine 1000 mg/m2 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/m2, 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/m2 was used in the expansion cohort, but was reduced to 60 mg/m2 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/m2 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.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2019 |
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Erschienen: |
2019 |
Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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Enthalten in: |
Cancers - 11(2019), 6 vom: 14. Juni |
Sprache: |
Englisch |
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Beteiligte Personen: |
Schokker, Sandor [VerfasserIn] |
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Links: |
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Themen: |
CapOx |
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Anmerkungen: |
Date Revised 29.09.2020 published: Electronic Citation Status PubMed-not-MEDLINE |
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doi: |
10.3390/cancers11060827 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM298243911 |
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245 | 1 | 0 | |a 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) |
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520 | |a 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/m2 on days 1 and 8, and capecitabine 1000 mg/m2 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/m2, 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/m2 was used in the expansion cohort, but was reduced to 60 mg/m2 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/m2 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 | ||
650 | 4 | |a Journal Article | |
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700 | 1 | |a van der Woude, Stephanie O |e verfasserin |4 aut | |
700 | 1 | |a van Kleef, Jessy Joy |e verfasserin |4 aut | |
700 | 1 | |a van Zoen, Daan J |e verfasserin |4 aut | |
700 | 1 | |a van Oijen, Martijn G H |e verfasserin |4 aut | |
700 | 1 | |a Mearadji, Banafsche |e verfasserin |4 aut | |
700 | 1 | |a Beenen, Ludo F M |e verfasserin |4 aut | |
700 | 1 | |a Stroes, Charlotte I |e verfasserin |4 aut | |
700 | 1 | |a Waasdorp, Cynthia |e verfasserin |4 aut | |
700 | 1 | |a Jibodh, R Aarti |e verfasserin |4 aut | |
700 | 1 | |a Creemers, Aafke |e verfasserin |4 aut | |
700 | 1 | |a Meijer, Sybren L |e verfasserin |4 aut | |
700 | 1 | |a Hooijer, Gerrit K J |e verfasserin |4 aut | |
700 | 1 | |a Punt, Cornelis J A |e verfasserin |4 aut | |
700 | 1 | |a Bijlsma, Maarten F |e verfasserin |4 aut | |
700 | 1 | |a van Laarhoven, Hanneke W M |e verfasserin |4 aut | |
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