Socinski M A, Clark J A, Halle J, Steagall A, Kaluzny B, Rosenman J G
Department of Medicine, University of North Carolina at Chapel Hill, 27514, USA.
Semin Oncol. 1997 Aug;24(4 Suppl 12):S12-117-S12-122.
Locally advanced non-small cell lung cancer is optimally managed with chemotherapy and thoracic irradiation, although the most appropriate strategy is not yet defined. In this phase I trial, we use two 21-day cycles of induction chemotherapy with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (225 mg/m2 over 3 hours) and carboplatin (area under the concentration-time curve = 6) followed by concurrent weekly paclitaxel (45 mg/m2/wk x 6) and carboplatin (area under the concentration-time curve = 2/wk x 6) and thoracic irradiation. Patients undergo three-dimensional treatment planning (conformal radiotherapy) to define the cancer target volume precisely. The phase I question being addressed in this study is the maximum tolerated radiation dose given concurrently with low-dose paclitaxel and carboplatin. The initial radiation dose is 60 Gy, with dose escalations to 66 Gy, 70 Gy, and 74 Gy being planned. Ten patients have been entered thus far (eight men and two women). Their median age is 67 years (range, 59 to 78 years), and none of the patients has had greater than 5% pretreatment weight loss. Seven of 10 are evaluable for response to induction carboplatin and paclitaxel, with a response rate of 57% (three partial responses and one minor response). Three patients had stable disease and none of the patients had evidence of progressive disease during induction chemotherapy. Three patients have completed all treatment at 60 Gy and one has completed all treatment at 66 Gy. Three of the four patients have had partial responses (75%), with the remaining patient having stable disease. Toxicity in the concurrent chemoradiotherapy portion of the trial thus far has consisted of grade 3 neutropenia in one patient and grade 4 lymphocytopenia in all four patients. No grade 3 or 4 nonhematologic toxicity has been seen. The trial data are not yet mature enough to report on survival. Accrual and treatment is continuing at the 66 Gy radiation dose level.
局部晚期非小细胞肺癌的最佳治疗方法是化疗和胸部放疗，尽管最合适的策略尚未明确。在这项I期试验中，我们采用两个21天周期的诱导化疗，使用紫杉醇（泰素；百时美施贵宝公司，新泽西州普林斯顿）（225mg/m²，静脉滴注3小时）和卡铂（浓度-时间曲线下面积=6），随后是每周一次的同步紫杉醇（45mg/m²/周×6次）和卡铂（浓度-时间曲线下面积=2/周×6次）以及胸部放疗。患者接受三维治疗计划（适形放疗）以精确界定肿瘤靶体积。本研究中要解决的I期问题是与低剂量紫杉醇和卡铂同步使用时的最大耐受放疗剂量。初始放疗剂量为60Gy，计划剂量递增至66Gy、70Gy和74Gy。到目前为止已入组10例患者（8例男性和2例女性）。他们的中位年龄为67岁（范围59至78岁），且所有患者治疗前体重减轻均未超过5%。10例患者中有7例可评估对诱导化疗中卡铂和紫杉醇的反应，有效率为57%（3例部分缓解和1例轻微缓解）。3例患者病情稳定，在诱导化疗期间无患者出现疾病进展的证据。3例患者已完成60Gy的所有治疗，1例已完成66Gy的所有治疗。4例患者中有3例出现部分缓解（75%），其余1例患者病情稳定。到目前为止，试验中同步放化疗部分的毒性反应包括1例3级中性粒细胞减少和所有4例患者出现4级淋巴细胞减少。未观察到3级或4级非血液学毒性。试验数据尚未成熟到足以报告生存情况。目前正在66Gy放疗剂量水平继续入组和治疗。
