TY - JOUR
T1 - 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)
AU - Schokker, Sandor
AU - van der Woude, Stephanie O.
AU - van Kleef, Jessy Joy
AU - van Zoen, Daan J.
AU - van Oijen, Martijn G. H.
AU - Mearadji, Banafsche
AU - Beenen, Ludo F. M.
AU - Stroes, Charlotte I.
AU - Waasdorp, Cynthia
AU - Jibodh, R. Aarti
AU - Creemers, Aafke
AU - Meijer, Sybren L.
AU - Punt, Cornelis J. A.
AU - Bijlsma, Maarten F.
AU - van Laarhoven, Hanneke W. M.
PY - 2019/6/1
Y1 - 2019/6/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85070641059&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31207904
U2 - https://doi.org/10.3390/cancers11060827
DO - https://doi.org/10.3390/cancers11060827
M3 - Article
C2 - 31207904
SN - 2072-6694
VL - 11
JO - Cancers
JF - Cancers
IS - 6
M1 - 827
ER -