Pneumology, Department of Medicine, Innenstadt, University of Munich, Germany.
Clin Lung Cancer. 2010 Jan;11(1):45-50. doi: 10.3816/CLC.2010.n.007.
Docetaxel consolidation therapy (DCT) after concurrent cisplatin/docetaxel chemoradiation therapy (CRT) produces high tumor control in non-small-cell lung cancer (NSCLC); toxicity is, however, considerable. We aimed to determine the maximally tolerated dose (MTD) for DCT.
Patients with inoperable stage IIIB NSCLC received docetaxel 20 mg/m2 and cisplatin 25 mg/m2 on days 1, 8, 15, 22, 29, and 36, with concurrent radiation therapy 5 days per week for a total dose of 66 Gy. Patients achieving stable disease, partial response, or complete response were given DCT on days 71, 92, and 113. DCT was started with 75 mg/m2 and titrated depending on tolerability. The MTD of docetaxel was defined as the dose preceding that at which 3 or more patients experienced dose-limiting toxicity (DLT).
Of 23 patients enrolled (median age, 58.8 years +/- 7.3 years), 19 received complete CRT (4 withdrew because of toxicity). Of the patients receiving complete CRT, 1 patient died and 1 became operable, leaving 17 patients eligible for DCT starting at 75 mg/m2. After the third patient with DLT, dose was reduced to 60 mg/m2. Median survival was 27.6 months +/- 23.1 months. Median TTP was 12.4 months +/- 10.7 months.
The MTD of DCT after concurrent cisplatin/docetaxel CRT was determined to be 60 mg/m2, but toxicity was considerable. The benefit-risk ratio of DCT has, however, been questioned by a placebo-controlled phase III trial. Further phase III trials need to consider further stratification factors (pretreatment forced expiratory volume [FEV]1, hemoglobin, performance, and stage) to define a role for DCT in patients with NSCLC.
多西紫杉醇巩固治疗（DCT）在顺铂/多西紫杉醇放化疗（CRT）后对非小细胞肺癌（NSCLC）有较高的肿瘤控制率，但毒性较大。我们的目的是确定 DCT 的最大耐受剂量（MTD）。
不可手术的 IIIB 期 NSCLC 患者接受多西紫杉醇 20 mg/m2 和顺铂 25 mg/m2，第 1、8、15、22、29 和 36 天，同时每周 5 天接受放疗，总剂量为 66 Gy。疾病稳定、部分缓解或完全缓解的患者在第 71、92 和 113 天接受 DCT。DCT 起始剂量为 75 mg/m2，并根据耐受性进行滴定。多西紫杉醇的 MTD 定义为 3 名或 3 名以上患者出现剂量限制毒性（DLT）的剂量。
23 名入组患者（中位年龄 58.8 岁 +/- 7.3 岁）中，19 名患者接受了完全 CRT（4 名因毒性退出）。接受完全 CRT 的患者中，1 名患者死亡，1 名患者可手术，17 名患者有资格接受 DCT，起始剂量为 75 mg/m2。在第 3 例发生 DLT 后，剂量减少至 60 mg/m2。中位生存期为 27.6 个月 +/- 23.1 个月。中位 TTP 为 12.4 个月 +/- 10.7 个月。
顺铂/多西紫杉醇 CRT 后 DCT 的 MTD 确定为 60 mg/m2，但毒性较大。然而，一项安慰剂对照的 III 期试验对 DCT 的获益风险比提出了质疑。进一步的 III 期试验需要考虑进一步的分层因素（治疗前用力呼气量[FEV1]、血红蛋白、表现和分期），以确定 DCT 在 NSCLC 患者中的作用。
