A phase I trial of the HIV protease inhibitor nelfinavir with concurrent chemoradiotherapy for unresectable stage IIIA/IIIB non-small cell lung cancer: a report of toxicities and clinical response.
A phase I trial of the HIV protease inhibitor nelfinavir with concurrent chemoradiotherapy for unresectable stage IIIA/IIIB non-small cell lung cancer: a report of toxicities and clinical response.
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DOI：
10.1097/jto.0b013e3182435aa6
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发表时间：
2012-04
期刊：
影响因子：
--
通讯作者：
Hahn SM
中科院分区：
文献类型：
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作者：
Rengan R;Mick R;Pryma D;Rosen MA;Lin LL;Maity AM;Evans TL;Stevenson JP;Langer CJ;Kucharczuk J;Friedberg J;Prendergast S;Sharkoski T;Hahn SM
这项I期试验的目的是确定局部晚期非小细胞肺癌（NSCLC）中放射增敏剂奈非那韦联合同步放化疗（CT-RT）的剂量限制性毒性（DLT）和最大耐受剂量。活检证实的IIIA或IIIB不可切除的NSCLC患者（患者）在CT-RT之前和同时接受奈非那韦（剂量水平（DL）1：625 mg PO BID，DL 2：1250 mg PO BID）给药7 - 14天。5例患者在DL 1接受治疗; 8例患者在DL 2接受治疗。患者同时接受CT-RT治疗，剂量为66.6Gy。DLT定义为需要中断治疗的任何治疗相关4级血液学毒性或3级或3级以上非血液学毒性（食管炎和肺炎除外）。16例患者入组，13例患者接受至少一剂奈非那韦。12例患者接受奈非那韦和同步放化疗治疗。在任一剂量水平下均未观察到DLT。因此，奈非那韦的最大耐受剂量为1250 mg PO BID。6例患者出现4级白细胞减少症。1例患者发生4级血小板减少症。所有12例缓解可评价患者的中位随访时间为31.6个月，存活者为23.5个月。12例患者中有9例具有可评价的治疗后PET/CT，代谢缓解如下：总体缓解：9/9（100%）;完全缓解：5/9（56%）;部分缓解4/9（44%）。在IIIA/IIIB期NSCLC患者中，奈非那韦与CT-RT同步给药的毒性可接受。代谢反应和肿瘤反应数据表明，奈非那韦在这种疾病中具有良好的活性。
The objective of this Phase I trial was to determine dose-limiting toxicities (DLT) and the maximally tolerated dose of the radiosensitizer Nelfinavir in combination with concurrent chemoradiotherapy (CT-RT) in locally advanced non-small cell lung cancer (NSCLC). Nelfinavir (Dose Level (DL) 1: 625mg PO BID, DL2:1250mg PO BID) was administered for 7 to 14 days prior to and concurrently with concurrent CT-RT to patients (pts) with biopsy confirmed IIIA or IIIB unresectable NSCLC. Five patients were treated at DL1; 8 patients were treated at DL2. Patients were treated with concurrent CT-RT to a dose of 66.6Gy. DLTs were defined as any treatment related Grade 4 hematologic toxicity requiring a break in therapy or non-hematologic Grade 3 or higher toxicity except esophagitis and pneumonitis. Sixteen patients were enrolled and 13 patients received at least one dose of nelfinavir. 12 patients were treated with nelfinavir and concurrent chemoradiotherapy. No DLTs have been observed at either dose level. The maximum tolerated dose of Nelfinavir was therefore 1250 mg PO BID. Six patients experienced Grade 4 leukopenia. One patient experienced grade 4 thromobcytopenia. Median follow-up for all 12 response-evaluable patients was 31.6 months and for survivors is 23.5 months. Nine of the 12 patients had evaluable post-treatment PET/CT with metabolic response as follows: overall response: 9/9 (100%); complete response: 5/9 (56%); partial response 4/9 (44%). Nelfinavir administered with concurrent CT-RT is associated with acceptable toxicity in stage IIIA/IIIB NSCLC. The metabolic response and tumor response data suggest that nelfinavir has promising activity in this disease.