Sarbajit Mukherjee, Yu Fujiwara, Christos Fountzilas, Harsha Pattnaik, Sarah Chatley, Deepak Vadehra, Moshim Kukar, Kristopher Attwood, Anthony George, Shailesh Advani, Han Yu, Kayla Catalfamo, Alyson Brown, Erik Spickard, Arkarachai Fungtammasan, Sagila George, Chih-Yi Liao, Renuka Iyer, Hassan Hatoum
{"title":"Trifluridine/Tipiracil和奥沙利铂作为诱导化疗治疗可切除的食管和胃食管交界处腺癌：一项II期研究","authors":"Sarbajit Mukherjee, Yu Fujiwara, Christos Fountzilas, Harsha Pattnaik, Sarah Chatley, Deepak Vadehra, Moshim Kukar, Kristopher Attwood, Anthony George, Shailesh Advani, Han Yu, Kayla Catalfamo, Alyson Brown, Erik Spickard, Arkarachai Fungtammasan, Sagila George, Chih-Yi Liao, Renuka Iyer, Hassan Hatoum","doi":"10.1002/cam4.70835","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Preoperative chemoradiation (CRT) followed by surgery for localized esophageal and gastroesophageal junction adenocarcinoma (EGAC) is a standard of care with a pathologic complete response (pCR) rate of 20%. We evaluated a novel combination of trifluridine/tipiracil with oxaliplatin as induction chemotherapy (IC) followed by CRT.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>We enrolled patients with potentially resectable localized EGAC (T3, T4aN0, or node-positive disease) in this open-label, single-arm, multicenter, Phase II trial between January 2020 and October 2022. Patients received three cycles of IC with trifluridine/tipiracil and oxaliplatin and then underwent concurrent CRT with weekly carboplatin and paclitaxel followed by surgery. The primary objective was to evaluate the pCR rate. The secondary objectives were to evaluate 2-year progression-free survival (PFS), 2-year overall survival (OS), and toxicities. Circulating tumor DNA (ctDNA) was measured at prespecified intervals to assess its correlation with clinical outcomes.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Of the 22 enrolled patients, 19 (86.4%) were male and 20 (90.9%) were Caucasian. The median age was 61 years, and 12 (54.5%) had their primary disease at the gastroesophageal junction. Twenty (90.9%) patients had T3 disease, and 15 (68.2%) had node-positive disease. Only two patients had pCRs, and an additional five had near pCRs. Since we could not meet our predefined pCR rate at the interim analysis, the study was closed. After a median follow-up of 15.8 months, 2-year OS and PFS were 43% and 41%, respectively. ctDNA clearance was associated with a significantly higher OS rate (<i>p</i> = 0.012) and PFS rate (<i>p</i> = 0.008). Nausea (59.1%) and fatigue (59.1%) were common treatment-related adverse events (AEs); nine (40.9%) patients had Grade 3 or higher AEs.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>IC with trifluridine/tipiracil and oxaliplatin followed by CRT did not improve pCR rate in resectable EGAC compared to pCR from previous reports with CRT alone. We found a correlation between ctDNA clearance and improved survival, which merits further investigation.</p>\n </section>\n \n <section>\n \n <h3> Clinical Trial Information</h3>\n \n <p>NCT04097028.</p>\n </section>\n </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 7","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70835","citationCount":"0","resultStr":"{\"title\":\"Trifluridine/Tipiracil and Oxaliplatin as Induction Chemotherapy in Resectable Esophageal and Gastroesophageal Junction Adenocarcinoma: A Phase II Study\",\"authors\":\"Sarbajit Mukherjee, Yu Fujiwara, Christos Fountzilas, Harsha Pattnaik, Sarah Chatley, Deepak Vadehra, Moshim Kukar, Kristopher Attwood, Anthony George, Shailesh Advani, Han Yu, Kayla Catalfamo, Alyson Brown, Erik Spickard, Arkarachai Fungtammasan, Sagila George, Chih-Yi Liao, Renuka Iyer, Hassan Hatoum\",\"doi\":\"10.1002/cam4.70835\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Preoperative chemoradiation (CRT) followed by surgery for localized esophageal and gastroesophageal junction adenocarcinoma (EGAC) is a standard of care with a pathologic complete response (pCR) rate of 20%. We evaluated a novel combination of trifluridine/tipiracil with oxaliplatin as induction chemotherapy (IC) followed by CRT.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>We enrolled patients with potentially resectable localized EGAC (T3, T4aN0, or node-positive disease) in this open-label, single-arm, multicenter, Phase II trial between January 2020 and October 2022. Patients received three cycles of IC with trifluridine/tipiracil and oxaliplatin and then underwent concurrent CRT with weekly carboplatin and paclitaxel followed by surgery. The primary objective was to evaluate the pCR rate. The secondary objectives were to evaluate 2-year progression-free survival (PFS), 2-year overall survival (OS), and toxicities. Circulating tumor DNA (ctDNA) was measured at prespecified intervals to assess its correlation with clinical outcomes.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Of the 22 enrolled patients, 19 (86.4%) were male and 20 (90.9%) were Caucasian. The median age was 61 years, and 12 (54.5%) had their primary disease at the gastroesophageal junction. Twenty (90.9%) patients had T3 disease, and 15 (68.2%) had node-positive disease. Only two patients had pCRs, and an additional five had near pCRs. Since we could not meet our predefined pCR rate at the interim analysis, the study was closed. After a median follow-up of 15.8 months, 2-year OS and PFS were 43% and 41%, respectively. ctDNA clearance was associated with a significantly higher OS rate (<i>p</i> = 0.012) and PFS rate (<i>p</i> = 0.008). Nausea (59.1%) and fatigue (59.1%) were common treatment-related adverse events (AEs); nine (40.9%) patients had Grade 3 or higher AEs.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>IC with trifluridine/tipiracil and oxaliplatin followed by CRT did not improve pCR rate in resectable EGAC compared to pCR from previous reports with CRT alone. 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Trifluridine/Tipiracil and Oxaliplatin as Induction Chemotherapy in Resectable Esophageal and Gastroesophageal Junction Adenocarcinoma: A Phase II Study
Background
Preoperative chemoradiation (CRT) followed by surgery for localized esophageal and gastroesophageal junction adenocarcinoma (EGAC) is a standard of care with a pathologic complete response (pCR) rate of 20%. We evaluated a novel combination of trifluridine/tipiracil with oxaliplatin as induction chemotherapy (IC) followed by CRT.
Methods
We enrolled patients with potentially resectable localized EGAC (T3, T4aN0, or node-positive disease) in this open-label, single-arm, multicenter, Phase II trial between January 2020 and October 2022. Patients received three cycles of IC with trifluridine/tipiracil and oxaliplatin and then underwent concurrent CRT with weekly carboplatin and paclitaxel followed by surgery. The primary objective was to evaluate the pCR rate. The secondary objectives were to evaluate 2-year progression-free survival (PFS), 2-year overall survival (OS), and toxicities. Circulating tumor DNA (ctDNA) was measured at prespecified intervals to assess its correlation with clinical outcomes.
Results
Of the 22 enrolled patients, 19 (86.4%) were male and 20 (90.9%) were Caucasian. The median age was 61 years, and 12 (54.5%) had their primary disease at the gastroesophageal junction. Twenty (90.9%) patients had T3 disease, and 15 (68.2%) had node-positive disease. Only two patients had pCRs, and an additional five had near pCRs. Since we could not meet our predefined pCR rate at the interim analysis, the study was closed. After a median follow-up of 15.8 months, 2-year OS and PFS were 43% and 41%, respectively. ctDNA clearance was associated with a significantly higher OS rate (p = 0.012) and PFS rate (p = 0.008). Nausea (59.1%) and fatigue (59.1%) were common treatment-related adverse events (AEs); nine (40.9%) patients had Grade 3 or higher AEs.
Conclusion
IC with trifluridine/tipiracil and oxaliplatin followed by CRT did not improve pCR rate in resectable EGAC compared to pCR from previous reports with CRT alone. We found a correlation between ctDNA clearance and improved survival, which merits further investigation.
期刊介绍：
Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas:
Clinical Cancer Research
Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations
Cancer Biology:
Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery.
Cancer Prevention:
Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach.
Bioinformatics:
Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers.
Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.
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