Varveris H, Mazonakis M, Vlachaki M, Kachris S, Lyraraki E, Zoras O, Maris T, Froudarakis M, Velegrakis J, Perysinakis C, Damilakis J, Samonis G
Department of Radiotherapy and Oncology, Heraklion University Hospital, Crete, Greece.
Oncol Rep. 2003 Jan-Feb;10(1):185-95. doi: 10.3892/or.10.1.185.
We conducted a phase I study to evaluate the activity and tolerability of concurrent docetaxel and cisplatinum radiosensitization with hyperfractionated irradiation, in patients with advanced non-small cell lung cancer (NSCLC) and squamous cell carcinoma of the head and neck (SCCHN). Nine patients (5 stage III(A) and 4 III(B)) with NSCLC, and 15 with SCCHN (10 stage III and 5 IV) were treated with a b.i.d. hyperfractionated (HF) radiotherapy schedule. The normalized total dose for alpha/beta ratio = 10 Gy was 69.6 Gy for NSCLC and 80.5 Gy for SCCHN patients. The standard dose of cisplatin (10 mg/m(2)) was given combined to docetaxel on a weekly basis. The docetaxel starting dose level was 10 mg/m(2)/week and was escalated by 3 mg/m(2) increments in cohorts of 8 patients (5 SCCHN and 3 NSCLC). DLT (grade 3 malaise) was observed in 4 out of 8 patients treated at the 16 mg/m(2)/week docetaxel dose level. The 13 mg/m(2)/week docetaxel dose level was defined as the MTD causing grade 3 mucositis in 4 out of 8 patients. In total 4 (17%) patients developed grade 3 neutropenia. G-CSF support was given in 1/8, 4/8, and 5/8 patients treated at the 10, 13 and 16 mg/m(2) docetaxel dose levels respectively. Fatigue was the most common adverse event (5/24: 21%) and was responsible for more than 1 week treatment delay in 4 out of 8 patients treated at the 16 mg/m(2)/week docetaxel dose level. Nine (3 NSCLC and 6 SCCHN patients: 37.5%) had treatment delay of 1 week, while 7 (3 NSCLC and 4 SCCHN: 29%) had delays of 2 weeks for combined chemoradiation sequelae. Acute hypersensitivity reactions occurred in 3 (12.5%) patients, and grade 3 mucositis in 2/8, 5/8 and 6/8 patients, treated at 10, 13 and 16 mg/m(2)/week docetaxel dose levels respectively. The overall response rate was 79% (CI = 63-96%) with 33% and 53% CRs for NSCLC and SCCHN patients respectively. There were 3 deaths among 9 NSCLC and 4 among 15 SCCHN patients. Local and/or distant disease recurrences were shown in 4 NSCLC and in 6 SCCHN patients; 5 NSCLC and 9 SCCHN patients are alive with no evidence of tumor progression at 8.5 months mean follow-up time. Radiosensitization with docetaxel and cisplatin given concurrently with HF (b.i.d.) radiotherapy on a weekly basis is a promising approach and the recommended dose for further phase II studies is 10 mg/m(2)/week for both drugs. The antitumor activity shown was significant in both types of tumors. The incorporation of docetaxel in chemoradiotherapy regimens for future treatment of squamous cell carcinoma of the lung and head and neck, merits evaluation in phase II and III trials.
我们开展了一项I期研究，以评估多西他赛和顺铂同步放疗增敏联合超分割照射，用于晚期非小细胞肺癌（NSCLC）和头颈部鳞状细胞癌（SCCHN）患者的活性和耐受性。9例NSCLC患者（5例III（A）期和4例III（B）期）以及15例SCCHN患者（10例III期和5例IV期）接受了每日两次的超分割（HF）放疗方案。对于α/β比值 = 10 Gy，NSCLC患者的归一化总剂量为69.6 Gy，SCCHN患者为80.5 Gy。顺铂标准剂量（10 mg/m²）每周与多西他赛联合使用。多西他赛起始剂量水平为10 mg/m²/周，每8例患者（5例SCCHN和3例NSCLC）一组，以3 mg/m²的增量递增。在多西他赛剂量水平为16 mg/m²/周治疗的8例患者中，有4例观察到剂量限制毒性（3级不适）。多西他赛剂量水平为13 mg/m²/周时被定义为最大耐受剂量，该剂量下8例患者中有4例出现3级粘膜炎。共有4例（17%）患者发生3级中性粒细胞减少。在多西他赛剂量水平为10、13和16 mg/m²治疗的患者中，分别有1/8、4/8和5/8的患者接受了粒细胞集落刺激因子支持治疗。疲劳是最常见的不良事件（5/24：21%），在多西他赛剂量水平为16 mg/m²/周治疗的8例患者中，有4例因疲劳导致治疗延迟超过1周。9例（3例NSCLC和6例SCCHN患者：37.5%）出现1周的治疗延迟，而7例（3例NSCLC和4例SCCHN：29%）因放化疗后遗症出现2周的延迟。3例（12.5%）患者发生急性超敏反应，在多西他赛剂量水平为10、13和16 mg/m²/周治疗的患者中，分别有2/8、5/8和6/8的患者出现3级粘膜炎。总体缓解率为79%（CI = 63 - 96%），NSCLC和SCCHN患者的完全缓解率分别为33%和53%。9例NSCLC患者中有3例死亡，15例SCCHN患者中有4例死亡。4例NSCLC患者和6例SCCHN患者出现局部和/或远处疾病复发；在平均随访8.5个月时，5例NSCLC患者和9例SCCHN患者存活且无肿瘤进展迹象。多西他赛和顺铂与HF（每日两次）放疗同步每周给药进行放疗增敏是一种有前景的方法，进一步II期研究的推荐剂量为两种药物均为10 mg/m²/周。在两种类型的肿瘤中均显示出显著的抗肿瘤活性。将多西他赛纳入肺癌和头颈部鳞状细胞癌未来治疗的放化疗方案中，值得在II期和III期试验中进行评估。
