Phase II study of neoadjuvant therapy with nab-paclitaxel and cisplatin followed by surgery in patients with locally advanced esophageal squamous cell carcinoma

Yun Fan, Youhua Jiang, Xinming Zhou, Qixun Chen, Zhiyu Huang, Yanjun Xu, Lei Gong, Haifeng Yu, Haiyan Yang, Jinshi Liu, Tao Lei, Qiang Zhao, Weimin Mao, Yun Fan, Youhua Jiang, Xinming Zhou, Qixun Chen, Zhiyu Huang, Yanjun Xu, Lei Gong, Haifeng Yu, Haiyan Yang, Jinshi Liu, Tao Lei, Qiang Zhao, Weimin Mao

Abstract

Background: We carried out a phase II study to evaluate the efficiency and safety of the combination of nanoparticle albumin bound-paclitaxel (nab-paclitaxel) and cisplatin as preoperative chemotherapy for locally advanced esophageal squamous cell carcinoma (ESCC)Results: From Oct 2011 to Dec 2012, 35 patients were enrolled and received neoadjuvant chemotherapy. Thirty patients underwent surgery and achieved a 100% R0 resection. Pathological complete response (pCR) rate was 13.3% and near pCR rate was 6.7%. Down-staging was achieved in 19 patients. With median follow-up of 37.8 months, 16 patients were still alive. One-, 2- and 3- year overall survival (OS) rate was 90.0%, 70.0% and 43.3%, respectively. This treatment resulted in a median disease-free survival (DFS) of 34.7 months and a median OS of 37.8 months. Median DFS and OS of down-staged patients were significantly longer than those of non-downstaged patients. The grade 4 toxicities during neoadjuvant chemotherapy were limited to neutropenia (2.9%) and vomiting (2.9%).

Methods: Patients with locally advanced ESCC (stage IIA to IIIC) and performance status 0-1 were enrolled and received two cycles of nab-paclitaxel (100 mg/m2) on day 1, 8, 22 and 29, and cisplatin (75 mg/m2) on day 1 and 22, followed by resection. Two cycles of adjuvant chemotherapy with the same regimen were given. Postoperative radiotherapy was permitted and decided by radiation therapist.

Conclusion: Weekly nab-paclitaxel with three-weekly cisplatin seems effective and safe as a neoadjuvant chemotherapy strategy for locally advanced ESCC. Down-staged patients have favorable outcome.ClinicalTrials.gov Identifier: NCT01258192.

Keywords: cisplatin; esophageal squamous cell carcinoma; esophagectomy; nab-paclitaxel; neoadjuvant chemotherapy.

Conflict of interest statement

The author has declared no conflicts of interest.

Figures

Figure 1. Study design
Figure 1. Study design
All patients had biopsy-proven resectable locally advanced squamous cell carcinoma of the middle third and distal third of esophagus and an ECOG Performance Status 0-1. All eligible patients received nab-PC (100 mg/m2, d1, d8, d22 and d29) and cisplatin (75 mg/m2, d1 and d22) as neoadjuvant chemotherapy, followed by esophagectomy and adjuvant chemotherapy with or without radiotherapy.
Figure 2. Study scheme
Figure 2. Study scheme
Total planned doses of nab-PC and cisplatin were administered in 35 patients. Five patients did not receive surgery after neoadjuvant chemotherapy, among them 2 suffered progressive disease, 3 refused surgery. Twenty-four patients accepted two cycles of adjuvant chemotherapy (CT) with the same regimen after surgery, and 7 patients received adjuvant radiotherapy after adjuvant chemotherapy (CRT).
Figure 3. Kaplan-Meier analysis of progression-free survival…
Figure 3. Kaplan-Meier analysis of progression-free survival (PFS) and overall survival (OS) of patients in different groups
Figure 3 A.-B. OS and DFS were not significantly different between patients with stage II and stage III disease. Figure 3 C.-D. Median OS and DFS of descent stage patients were significantly longer than of no descent stage patients. Figure 3 E.-F. Median OS and DFS were longer in pCR patients than in non-pCR patients but that difference did not reach significance.

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