1. 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
- Author
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Gerrit K. J. Hooijer, Sandor Schokker, Maarten C.C.M. Hulshof, Sybren L. Meijer, Charlotte I. Stroes, Stephanie O. van der Woude, Nadia Haj Mohammad, Cecile Grootscholten, Remco J. Molenaar, Mark I. van Berge Henegouwen, Jelle P Ruurda, Hanneke W. M. van Laarhoven, Ron A. A. Mathôt, Geert-Jan Creemers, Grard A. P. Nieuwenhuijzen, Rob H.A. Verhoeven, Johanna W. van Sandick, Annemieke Cats, Maarten F. Bijlsma, João P. Belo Pereira, Graduate School, Oncology, Pharmacy, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Center of Experimental and Molecular Medicine, Radiotherapy, Pathology, CCA - Cancer Treatment and Quality of Life, Surgery, APH - Methodology, APH - Quality of Care, Internal medicine, Radiation Oncology, and VU University medical center
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0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,esophageal adenocarcinoma ,medicine.medical_treatment ,Phases of clinical research ,Gastroenterology ,lcsh:RC254-282 ,Article ,predictive biomarkers ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,proteomics ,Internal medicine ,Medicine ,S-1 pharmacokinetics ,Chemotherapy ,business.industry ,oxaliplatin ,Area under the curve ,S-1 ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Carboplatin ,Oxaliplatin ,adjuvant chemotherapy ,030104 developmental biology ,Oncology ,chemistry ,Esophagectomy ,030220 oncology & carcinogenesis ,Biomarker (medicine) ,business ,Adjuvant ,medicine.drug - Abstract
We assessed the feasibility of adjuvant S-1 and oxaliplatin following neoadjuvant chemoradiotherapy (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.
- Published
- 2021
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