Bonomi P, Siddiqui S, Lincoln S, Sharma M, Recine D, Warren W, Faber L P
Department of Radiation Therapy, Rush University Medical Center, Chicago, IL, USA.
Semin Oncol. 1996 Dec;23(6 Suppl 16):102-7.
We have evaluated escalating doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in combination with carboplatin, cisplatin, etoposide, and concurrent thoracic radiotherapy in patients with stage III non-small cell lung cancer. Dose-limiting toxicity was observed at paclitaxel 90 mg/m2. Subsequent modifications resulted in a new regimen, which consists of a 3-hour paclitaxel infusion on day 1 (three dose levels: 80, 100, and 120 mg/m2), etoposide 40 mg/m2 intravenously over 1 hour daily on days 2 to 5, and carboplatin given at an area under the concentration-time curve of 4 mg/mL x min on day 1 after paclitaxel. Treatment courses were repeated every 28 days. Eleven patients considered eligible for surgery received two courses. Nonsurgical patients (five) received three courses. No episodes of grade > or = 3 nausea and vomiting, dermatitis, anorexia, esophagitis, or thrombocytopenia were observed. The dose-limiting toxicity (grade 4 granulocytopenia) occurred in three of five patients at 120 mg/m2 paclitaxel (level 3). Grade 3 radiation pneumonitis was observed in three patients. Nine patients have undergone pulmonary resection: four pneumonectomies, four lobectomies, and one segmental resection. No operative deaths, respiratory insufficiency, or cardiovascular complications were observed. Clinical partial remissions have been observed in 11 of 16 patients overall, and two histologic complete remissions were achieved in nine surgical patients. Our preliminary results show that pulmonary resection is feasible following treatment with radiation and concurrent paclitaxel-containing chemotherapy. Although the maximum tolerated paclitaxel dose in the present study was relatively low, favorable initial responses warrant further study of paclitaxel-containing combination chemotherapy and concurrent radiation. We next plan to delete etoposide from our chemoradiotherapy regimen and escalate the paclitaxel dose.
我们评估了递增剂量的紫杉醇（泰素；百时美施贵宝公司，新泽西州普林斯顿）联合卡铂、顺铂、依托泊苷以及同步胸部放疗用于Ⅲ期非小细胞肺癌患者的疗效。在紫杉醇剂量为90mg/m²时观察到剂量限制性毒性。随后的调整产生了一种新方案，该方案包括在第1天进行3小时的紫杉醇静脉输注（三个剂量水平：80、100和120mg/m²），在第2至5天每天1小时静脉输注依托泊苷40mg/m²，以及在第1天紫杉醇输注后给予卡铂，其浓度 - 时间曲线下面积为4mg/mL×min。治疗疗程每28天重复一次。11名被认为适合手术的患者接受了两个疗程的治疗。非手术患者（5名）接受了三个疗程的治疗。未观察到≥3级的恶心、呕吐、皮炎、厌食、食管炎或血小板减少的发作。在5名接受120mg/m²紫杉醇（第3水平）治疗的患者中有3名出现了剂量限制性毒性（4级粒细胞减少）。3名患者观察到3级放射性肺炎。9名患者接受了肺切除术：4例全肺切除术、4例肺叶切除术和1例肺段切除术。未观察到手术死亡、呼吸功能不全或心血管并发症。在总共16名患者中有11名观察到临床部分缓解，在9名手术患者中有2名实现了组织学完全缓解。我们的初步结果表明，放疗联合含紫杉醇的同步化疗后进行肺切除术是可行的。尽管本研究中紫杉醇的最大耐受剂量相对较低，但良好的初始反应值得进一步研究含紫杉醇的联合化疗和同步放疗。我们接下来计划从我们的放化疗方案中去除依托泊苷并提高紫杉醇剂量。
