Prospective study of daily low-dose nedaplatin and continuous 5-fluorouracil infusion combined with radiation for the treatment of esophageal squamous cell carcinoma

Satoshi Osawa, Takahisa Furuta, Ken Sugimoto, Takashi Kosugi, Tomohiro Terai, Mihoko Yamade, Yasuhiro Takayanagi, Masafumi Nishino, Yasushi Hamaya, Chise Kodaira, Takanori Yamada, Moriya Iwaizumi, Kosuke Takagaki, Ken-ichi Yoshida, Shigeru Kanaoka, Mutsuhiro Ikuma, Satoshi Osawa, Takahisa Furuta, Ken Sugimoto, Takashi Kosugi, Tomohiro Terai, Mihoko Yamade, Yasuhiro Takayanagi, Masafumi Nishino, Yasushi Hamaya, Chise Kodaira, Takanori Yamada, Moriya Iwaizumi, Kosuke Takagaki, Ken-ichi Yoshida, Shigeru Kanaoka, Mutsuhiro Ikuma

Abstract

Background: Protracted low-dose concurrent chemotherapy combined with radiation has been proposed for enhanced treatment results for esophageal cancer. We evaluated the efficacy and the toxicity of a novel regimen of daily low-dose nedaplatin (cis-diammine-glycolatoplatinum) and continuous infusion of 5-fluorouracil (5-FU) with radiation in patients with esophageal squamous cell carcinoma.

Methods: Between January 2003 and June 2008, 33 patients with clinical stage I to IVB esophageal squamous cell carcinoma were enrolled. Nedaplatin (10 mg/body/day) was administered daily and 5-FU (500 mg/body/day) was administered continuously for 20 days. Fractionated radiotherapy for a total dose of 50.4-66 Gy was administered together with chemotherapy. Additional chemotherapy with nedaplatin and 5-FU was optionally performed for a maximum of 5 courses after chemoradiotherapy. The primary end-point of this study was to evaluate the tumor response, and the secondary end-points were to evaluate the toxicity and the overall survival.

Results: Twenty-two patients (72.7%) completed the regimen of chemoradiotherapy. Twenty patients (60.6%) achieved a complete response, 10 patients (30.3%) a partial response. One patient (3.0%) had a stable disease, and 2 (6.1%) a progressive disease. The overall response rate was 90.9% (95% confidence interval: 75.7%-98.1%). For grade 3-4 toxicity, leukopenia was observed in 75.8% of the cases, thrombocytopenia in 24.2%, anemia in 9.1%, and esophagitis in 36.4%, while late grade 3-4 cardiac toxicity occurred in 6.1%. Additional chemotherapy was performed for 26 patients (78.8%) and the median number of courses was 3 (range, 1-5). The 1-, 2- and 3-year survival rates were 83.9%, 76.0% and 58.8%, respectively. The 1- and 2-year survival rates were 94.7% and 88.4% in patients with T1-3 M0 disease, and 66.2% and 55.2% in patients with T4/M1 disease.

Conclusion: The treatment used in our study may yield a high complete response rate and better survival for each stage of esophageal squamous cell carcinoma.

Trial registration: ClinicalTrials.gov Identifier: NCT00197444.

Figures

Figure 1
Figure 1
Survival rate calculated by the Kaplan-Meier method. (A) Overall survival among all patients. (B) Comparison between T1-3 M0 and T4/M1 groups. (C) Comparison between groups of patients with and without lymph node metastasis.
Figure 2
Figure 2
The effects of treatment completion or additional adjuvant chemotherapy on survival rate. (A) Comparison between groups that did and groups that did not complete the treatment. (B) Comparison between groups with or without additional chemotherapy after the initial chemoradiotherapy. CT, chemotherapy.

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