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


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


BACKGROUND
ClinicalTrials.gov Identifier: NCT00197444.
Osawa
Satoshi
S
First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan. sososawa@hama-med.ac.jp
Furuta
Takahisa
T
Sugimoto
Ken
K
Kosugi
Takashi
T
Terai
Tomohiro
T
Yamade
Mihoko
M
Takayanagi
Yasuhiro
Y
Nishino
Masafumi
M
Hamaya
Yasushi
Y
Kodaira
Chise
C
Yamada
Takanori
T
Iwaizumi
Moriya
M
Takagaki
Kosuke
K
Yoshida
Ken-ichi
K
Kanaoka
Shigeru
S
Ikuma
Mutsuhiro
M
D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D011878:Radiotherapy; D016896:Treatment Outcome
D009944:Organoplatinum Compounds; C053989:nedaplatin; D005472:Fluorouracil