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

Erscheinungsjahr:

2019

Erschienen:

2019

Enthalten in:

Zur Gesamtaufnahme - volume:11

Enthalten in:

Cancers - 11(2019), 6 vom: 14. Juni

Sprache:

Englisch

Beteiligte Personen:

Schokker, Sandor [VerfasserIn]
van der Woude, Stephanie O [VerfasserIn]
van Kleef, Jessy Joy [VerfasserIn]
van Zoen, Daan J [VerfasserIn]
van Oijen, Martijn G H [VerfasserIn]
Mearadji, Banafsche [VerfasserIn]
Beenen, Ludo F M [VerfasserIn]
Stroes, Charlotte I [VerfasserIn]
Waasdorp, Cynthia [VerfasserIn]
Jibodh, R Aarti [VerfasserIn]
Creemers, Aafke [VerfasserIn]
Meijer, Sybren L [VerfasserIn]
Hooijer, Gerrit K J [VerfasserIn]
Punt, Cornelis J A [VerfasserIn]
Bijlsma, Maarten F [VerfasserIn]
van Laarhoven, Hanneke W M [VerfasserIn]

Links:

Volltext

Themen:

CapOx
Esophagogastric cancer
Journal Article
Nab-paclitaxel
Phase I clinical trial
Stromal cells

Anmerkungen:

Date Revised 29.09.2020

published: Electronic

Citation Status PubMed-not-MEDLINE

doi:

10.3390/cancers11060827

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM298243911