A phase ii study demonstrates no feasibility of adjuvant treatment with six cycles of s-1 and oxaliplatin in resectable esophageal adenocarcinoma, with ercc1 as biomarker for response to sox

Charlotte I. Stroes, Sandor Schokker, Remco J. Molenaar, Ron A. A. Mathôt, Maarten F. Bijlsma, Stephanie O. van der Woude, João P. Belo Pereira, Gerrit K. J. Hooijer, Rob H. A. Verhoeven, Annemieke Cats, Cecile Grootscholten, Johanna W. van Sandick, Geert-Jan Creemers, Grard A. P. Nieuwenhuijzen, Nadia Haj Mohammad, Jelle P. Ruurda, Sybren L. Meijer, Maarten C. C. M. Hulshof, Mark I. van Berge Henegouwen, Hanneke W. M. van Laarhoven*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

We assessed the feasibility of adjuvant S-1 and oxaliplatin following neoadjuvant chemora-diotherapy (nCRT) and esophagectomy. Patients treated with nCRT (paclitaxel, carboplatin) and esophagectomy received six 21-day cycles with oxaliplatin (130 mg/m2) on day 1 and S-1 (25 mg/m2 twice daily) on days 1–14. The primary endpoint was feasibility, defined as ≥50% completing treatment. We performed exploratory propensity-score matching to compare survival, ERCC1 and Thymidylate Synthase (TS) immunohistochemistry analyses, proteomics biomarker discovery and 5-FU pharmacokinetic analyses. Forty patients were enrolled and 48% completed all adjuvant cycles. Median dose intensity was 98% for S-1 and 62% for oxaliplatin. The main reason for early discontinuation was toxicity (67%). The median recurrence-free and overall survival were 28.3 months and 40.8 months, respectively (median follow-up 29.1 months). Survival was not significantly prolonged compared to a matched cohort (p = 0.09). Patients with ERCC1 negative tumor expression had significantly better survival compared to ERCC1 positivity (p = 0.01). Our protein signature model was predictive of survival [p = 0.04; Area under the curve (AUC) 0.80]. Moreover, 5-FU pharmacokinetics significantly correlated with treatment-related toxicity. To conclude, six cycles adjuvant S-1 and oxaliplatin were not feasible in pretreated esophageal adenocarcinoma. Although the question remains whether additional treatment with chemotherapy should be provided in the adjuvant setting, subgroups such as patients with ERCC1 negativity could potentially benefit from adjuvant SOX based on our exploratory biomarker research.
Original languageEnglish
Article number839
Pages (from-to)1-15
Number of pages15
JournalCancers
Volume13
Issue number4
DOIs
Publication statusPublished - 1 Feb 2021

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