title: A modified Phase I trial of radiation dose escalation in 3D conformal radiation therapy with concurrent vinorelbine and carboplatin chemotherapy for non-small-cell lung cancer.
abstract: The Radiation Therapy Oncology Group reported a maximum tolerated dose of 74 Gy for patients with non-small cell lung cancer (NSCLC); however, it was unclear whether this dose could be safely administered to Asian patients due to differences in their physique compared to Western patients. We therefore conducted a modified Phase I trial to determine whether 70 Gy could be safely delivered to Chinese patients with NSCLC undergoing 3D-conformal radiation therapy (3D-CRT) with concurrent chemotherapy. Previously untreated NSCLC patients received 3D-CRT (2 Gy/day, 5 fractions per week). Three dose levels were examined: 62, 66 and 70 Gy. Two cycles of concurrent chemotherapy (vinorelbine and carboplatin) were started on the first day of radiation therapy. Dose-limiting toxicity (DLT) was defined as severe or life-threatening side effects that altered the continued implementation of chemoradiotherapy. Among the 19 patients recruited in this study, most of the haematologic and non-haematologic toxicities were mild to moderate and clinically manageable. Only one patient, in the 70 Gy cohort, experienced a DLT of Grade 3 radiation-induced pneumonia. The overall response rate was 77.8% (14/18). The median progression-free survival (PFS) was 12 months, and the 1-year PFS was 37.6%. Our results support both the feasibility of incorporating 3D-CRT with concurrent vinorelbine and carboplatin and a dose escalation to 70 Gy for Chinese patients with NSCLC, based on the acceptable toxicity and encouraging overall response and survival rates. A further evaluation of this regimen in a prospective Phase II trial is ongoing.
authors.affiliation: Department of Oncology, Hebei Medical University North China Petroleum Bureau General Hospital, 8 Huizhan Avenue, Renqiu 062552, Hebei, China. linqiang@csco.org.cn
authors.forename: Qiang
authors.initials: Q
authors.lastname: Lin
authors.forename: Yue'e
authors.initials: Y
authors.lastname: Liu
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Huang
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Ge
authors.forename: Xiaocang
authors.initials: X
authors.lastname: Ren
authors.forename: Xueji
authors.initials: X
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Guo
authors.forename: Yannan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Junichi
authors.initials: J
authors.lastname: Asaumi
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000628:therapy*; D059248:Chemoradiotherapy; D019583:Dose Fractionation, Radiation; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000628:therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011832:Radiation Injuries / Q000209:etiology* / Q000517:prevention & control; D020266:Radiotherapy, Conformal / Q000009:adverse effects*; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D014747:Vinblastine; D016190:Carboplatin; D000077235:Vinorelbine