A phase I study of concurrent chemotherapy and thoracic radiotherapy with oral epigallocatechin-3-gallate protection in patients with locally advanced stage III non-small-cell lung cancer.
OBJECTIVE
Patients with unresectable stage III non-small-cell lung cancer receiving concurrent chemoradiotherapy often develop esophagitis that may lead to unplanned treatment interruptions, which may severely reduce rates of locoregional tumor control and survival. No effectivetreatment that would reduce the incidence and severity of this complication has been identified up to now. Although acceleration of normal tissue protection using epigallocatechin-3-gallate (EGCG) has been reported, its actual clinical practicability remains obscure.


METHODS
This is a phase I study of EGCG in combination with standard chemoradiation in surgically unresectable stage III non-small-cell lung cancer. Chemotherapy (cisplatin and etoposide) was given concurrently with radiation. EGCG solution was swallowed three times a day after the occurrence of grade 2 esophagitis at six concentration levels and dose escalation followed a standard phase I design. Esophageal toxicity and patient-reported pain was recorded weekly.


RESULTS
Twenty-four patients with AJCC stage IIIA (six) and IIIB (eighteen) completed the course of therapy. Twelve had squamous histology, ten adenocarcinoma, and two not specified. Patients were treated in six cohorts at six dose levels of EGCG. RT was not interrupted with a median dose of 64 Gy. There were no dose-limiting toxicities reported in all EGCG dosing tiers. Dramatic regression of esophagitis to grade 0/1 was observed in 22 of 24 patients, whereas grade 2 esophagitis persisted in 2 of 24 patients at the end of radiotherapy. The pain score was also reduced from a mean of 4.58 (N=24), 1.29 (N=24), 1.42 (N=24), 0.96 (N=23) to 1.13 (N=16) every week in turn.


CONCLUSIONS
We conclude that the oral administration of EGCG is feasible, safe and effective. The phase II recommended concentration is 440 μmol/L.
Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan, China. Electronic address: zhx87520052@163.com.
Hanxi
H
Zhao
Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan, China. Electronic address: wanqi5145@126.com.
Wanqi
W
Zhu
Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan, China.
Peng
P
Xie
Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan, China.
Huiqin
H
Li
Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan, China.
Xiqin
X
Zhang
Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital, Jinan, China.
Xiaorong
X
Sun
Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan, China.
Jinming
J
Yu
Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan, China. Electronic address: wanqi5145@163.com.
Ligang
L
Xing
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D004941:Esophagitis / Q000209:etiology / Q000517:prevention & control; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011879:Radiotherapy Dosage
D005047:Etoposide; D002392:Catechin; C045651:epigallocatechin gallate; D002945:Cisplatin
EGCG; Non-small-cell lung cancer; Phase I study