title: Neoadjuvant chemotherapy followed by late-course accelerated hyperfractionated radiation therapy for locally advanced non-small-cell lung cancer: long-term results of a phase I/II clinical trial.
abstract: Toxicity, response, and long-term results of a definitive chemotherapy/radiation therapy (RT) protocol in patients with unresectable stage III non-small-cell lung cancer (NSCLC) were evaluated. Two cycles of cisplatin-based chemotherapy were delivered before RT, and another 2 cycles were added for patients who responded to the first 2 cycles of chemotherapy. The first course of radiation covered the primary lesion and elective nodal regions, given in 2 Gy per fraction, 5 days a week for a dose of 40 Gy. Late-course hyperfractionated accelerated RT was delivered to the gross tumor twice a day for an additional 27 Gy within 2 weeks, using 1.5 Gy per fraction. Fifty-three patients with unresectable stage IIIA (N2) and IIIB NSCLC were eligible for analysis. Twelve patients developed grade 3 neutropenia, and 3 patients developed grade 4 neutropenia. Grade 2 or 3 esophagitis was observed in 14 and 2 patients, respectively, and grade 2 or 3 pneumonitis was observed in 9 and 1 patient, respectively. Six patients developed grade 2 and 1 patient developed grade 3 late lung toxicity. The median survival time was 15.5 months. Twenty-six of 53 patients (49%) have died of locoregional progression inside the thorax. The distant metastasis rate was 59.5% (22 of 37 patients) for those who did not respond to chemotherapy and 18.8% (3 of 16 patients) for those who responded to chemotherapy (P = 0.006). Late-course hyperfractionated accelerated RT combined with induction chemotherapy was well tolerated and yielded long-term results that compare favorably with those of studies using 2 cycles of induction chemotherapy and conventional fractionated RT. However, local control was still discouraging.
authors.affiliation: Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China. gzcm@263.net
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Chen
authors.forename: Yong
authors.initials: Y
authors.lastname: Bao
authors.forename: Chao-Gui
authors.initials: CG
authors.lastname: Xian
authors.forename: Guo-Zhen
authors.initials: GZ
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Guang-Chuan
authors.initials: GC
authors.lastname: Xu
authors.forename: Xiao-Wu
authors.initials: XW
authors.lastname: Deng
authors.forename: Tai-Xiang
authors.initials: TX
authors.lastname: Lu
authors.forename: Jian-Yang
authors.initials: JY
authors.lastname: Qian
authors.forename: Nian-Ji
authors.initials: NJ
authors.lastname: Cui
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D016019:Survival Analysis; D016896:Treatment Outcome