Adjuvant sunitinib following chemoradiotherapy (CRT) and surgery for esophageal cancer: A phase II trial

Abstract

e15550 Background: Locally advanced esophageal cancer (LAEC) has a 5-year survival of < 30 %. Most patients (pts) fail after curative intent tri-modality treatment with distant metastatic disease. This phase II trial aims to determine if adjuvant targeted therapy, after neoadjuvant CRT plus surgery for resectable LAEC, may impact on systemic disease without significant toxicity. Methods: Pts with LAEC of the thoracic esophagus or gastroesophageal junction, ECOG PS 0,1 and surgical candidates treated with: preoperative Irinotecan (65mg/m2 initially, ammended to 50mg/m2) + Cisplatin (30mg/m2) on weeks 1,2,4,5,7,8 + concurrent conformal radiotherapy (50Gy/25 fractions) on weeks 4–8. Esophagectomy during weeks 15–18. Sunitinib 37.5mg daily (escalating to 50mg daily if tolerated) commenced 4–12 weeks post surgery, for 1 year. Primary endpoint is feasibility and efficacy of adjuvant sunitinib. Planned sample size 36pts. Results: 30pts enrolled from 11/06 to 12/08. Median age 64 yr (43–71), male: 22, adenocarcinoma: squamous 22:6; 10 pts stage IIA, 5 IIB and 13 III. 2 pts excluded with positive PET scan. 28 pts completed CRT - 18 pts (64%) received ≥80% of planned chemotherapy dose, 23 pts (82%) received full radiation dose. Grade 3/4 toxicity included: neutropenia (17/28), diarrhea (7/28), dehydration (4/28), febrile neutropenia (FN) (3/28) and nausea (2/28). 2 deaths on chemotherapy (1 bacterial meningitis, 1 FN) leading to irinotecan dose- reduction. Dysphagia improved in 14/23 pts during CRT. 18 pts have undergone esophagectomy. Complete pathological response in 4 (22%), downstaging in 3 (17%), stable disease in 11 (61%). 2 pts unresectable (metastases at laparotomy). 1 post-operative death due to pulmonary embolus. 9 pts have commenced sunitinib, 6 maintained at starting dose of 37.5mg; 2 dose reductions; 1 discontinued with poor wound healing. Grade 3 toxicity included: leukopenia (2/9), hand-foot reaction (1/9) and depression (1/9). Conclusions: In LAEC, induction Irinotecan/Cisplatin and radiotherapy followed by esophagectomy is associated with a significant but manageable toxicity profile. Early initiation of sunitinib is feasible and well-tolerated. Updated results to be presented. No significant financial relationships to disclose.

Research Progress in Targeted Therapy for Esophageal Cancer

“…Sunitinib is an oral multi-kinase inhibitor that targets VEGFR, platelet-derived growth factor receptor (PDGFR), and others. A phase II trial showed no therapeutic benefit of postoperative adjuvant therapy with sunitinib in combination with chemoradiotherapy in patients with locally advanced EC [36]. Another phase II trial found a trend toward improved OS with sunitinib in combination with FOLFIRII (irinotecan, 5-fluorouracil , and folic acid) in patients with advanced refractory esophageal cancer [37].…”

Review: Integration of targeted agents in the neo-adjuvant treatment of gastro-esophageal cancers

“…Abstract reports in the metastatic and adjuvant settings are available. The University Health Network of Toronto has reported early feasibility data from a phase II trial (abstract form) on adjuvant sunitinib in surgically resected stage II or III esophageal cancer patients after neo-adjuvant cisplatin/ irinotecan [Horgan et al 2009]. A phase II trial has been reported (abstract form) on the combination of sorafenib and docetaxel/cisplatin in metastatic or advanced gastric/GEJ cancer.…”