Induction Therapy for Locally Advanced, Resectable Esophagogastric Cancer

Patrick M. Boland, Joshua E. Meyer, Adam C. Berger, Steven J. Cohen, Tzahi Neuman, Harry S. Cooper, Anthony J. Olszanski, Monica Davey, Jonathan D. Cheng, Abraham Lebenthal, Barbara A. Burtness, Walter J. Scott, Igor A. Astsaturov*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Preoperative chemotherapy and radiation for localized esophageal cancer produces cure rates near 30% when combined with surgical resection. Vandetanib, a small molecule receptor tyrosine kinase inhibitor of VEGFR-2, VEGFR-3, RET, and EGFR, demonstrated synergy with radiation and chemotherapy in preclinical models. We conducted a phase I study to assess the safety and tolerability of vandetanib when combined with preoperative chemoradiation in patients with localized esophageal carcinoma who were surgical candidates. Methods: Patients with stage II-III esophageal and gastroesophageal junction carcinoma without prior therapy were enrolled in a 3+3 phase I design. Patients received once-daily vandetanib (planned dosing levels of 100, 200, and 300 mg) with concomitant daily radiotherapy (1.8 Gy/d, 45 Gy total) and chemotherapy, consisting of infusional 5-FU (225 mg/m 2/d over 96 h, weekly), paclitaxel (50 mg/m 2, days 1, 8, 15, 22, 29) and carboplatin (AUC of 5, days 1, 29). Results: A total 9 patients were enrolled with 8 having either distal esophageal or gastroesophageal junction carcinomas. All patients completed the planned preoperative chemoradiation and underwent esophagectomy. Nausea (44%) and anorexia (44%) were the most common acute toxicities of any grade. One grade 4 nonhematologic toxicity was observed (gastrobronchial fistula). One additional patient suffered a late complication, a fatal aortoenteric hemorrhage, not definitively related to the investigational regimen. Five (56%) patients achieved a pathologic complete response. Three (33%) additional patients had only microscopic residual disease. Five (56%) patients remain alive and disease free with a median follow-up of 3.7 years and median overall survival of 3.2 years. The maximum tolerated dose was vandetanib 100 mg/d. Conclusions: Vandetanib at 100 mg daily is tolerable in combination with preoperative chemotherapy (5-FU, paclitaxel, carboplatin) and radiation therapy with encouraging efficacy worthy of future study.

Original languageEnglish
Pages (from-to)393-398
Number of pages6
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Volume40
Issue number4
DOIs
StatePublished - 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 Wolters Kluwer Health, Inc.

Keywords

  • 5-fluorouracil
  • carboplatin
  • esophageal cancer
  • paclitaxel
  • radiotherapy
  • surgery
  • vandetanib

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