Cohen Ezra E W, Rosine Dominique, Haraf Daniel J, Loh Elwyn, Shen Liji, Lusinchi Antoine, Vokes Everett E, Bourhis Jean
Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA.
Int J Radiat Oncol Biol Phys. 2007 Mar 1;67(3):678-84. doi: 10.1016/j.ijrobp.2006.09.056.
Reirradiation (re-RT) with concurrent chemotherapy offers a therapeutic option in patients who have locoregional recurrence of head and neck cancer (HNC). The hypoxic cell sensitizer, tirapazamine (TPZ), has demonstrated promising results in first-line therapy for HNC. This phase I trial was designed to test the feasibility of giving TPZ in the re-RT setting.
Patients with recurrent HNC who received prior radiotherapy (RT) were enrolled and received TPZ (260 mg/m2) and cisplatin (50 mg/m2) Weeks 1, 3, and 5 concurrently with RT (72 Gy, 42 fractions over 6 weeks). TPZ (160 mg/m2) alone was added on Days 1, 3, and 5 of Week 2 (cohort 1) or Weeks 2 and 4 (cohort 2).
Twenty-five subjects were enrolled, 7 and 18 on cohorts 1 and 2, respectively. Significant toxicities included Grade 3 dermatitis (20%) and Grade 3 mucositis (40%). Dose-limiting toxicity was observed on cohort 2 (1 patient with aspiration pneumonia). Four deaths occurred during treatment. Two fatalities occurred after completing therapy as a result of carotid artery rupture. With a minimum and median follow-up of 14 and 24 months, respectively, median overall survival was 14 months with actuarial 1-year and 2-year survival of 56% and 27%, respectively.
Reirradiation with concomitant chemotherapy including TPZ in patients with unresectable recurrent HNC is feasible and results in long-term survival in a significant proportion of patients.
对头颈部癌（HNC）局部区域复发的患者，再程放疗（re-RT）联合化疗是一种治疗选择。乏氧细胞增敏剂替拉扎明（TPZ）在HNC一线治疗中已显示出有前景的结果。本I期试验旨在测试在再程放疗环境中给予TPZ的可行性。
纳入先前接受过放疗（RT）的复发性HNC患者，在第1、3和5周同时接受TPZ（260mg/m²）和顺铂（50mg/m²），同时进行放疗（72Gy，6周内分42次）。在第2周的第1、3和5天（队列1）或第2周和第4周（队列2）单独添加TPZ（160mg/m²）。
共纳入25名受试者，队列1和队列2分别为7名和18名。显著毒性包括3级皮炎（20%）和3级黏膜炎（40%）。在队列2观察到剂量限制性毒性（1例患者发生吸入性肺炎）。治疗期间发生4例死亡。2例死亡发生在完成治疗后，原因是颈动脉破裂。分别进行了至少14个月和中位24个月的随访，中位总生存期为14个月，1年和2年精算生存率分别为56%和27%。
对于不可切除的复发性HNC患者，再程放疗联合包括TPZ在内的化疗是可行的，并且相当比例的患者可实现长期生存。
