Groen H J, Fokkema E, Biesma B, Kwa B, van Putten J W, Postmus P E, Smit E F
Department of Pulmonary Diseases, University Hospital, Groningen, The Netherlands.
J Clin Oncol. 1999 Mar;17(3):927-32. doi: 10.1200/JCO.1999.17.3.927.
To evaluate the efficacy of paclitaxel and carboplatin (PC) in small-cell lung cancer (SCLC) patients resistant to cyclophosphamide, doxorubicin, and etoposide (CDE).
We performed a phase II study with PC in SCLC patients who relapsed within 3 months after first-line treatment with CDE. Paclitaxel administration (175 mg/m2 by a 3-hour intravenous infusion) was followed by a 30-minute infusion of carboplatin (area under the curve 7; Chatelut formula) once every 3 weeks for five cycles. Dexamethasone, clemastine, and ranitidine were standard premedication before every cycle.
Included were 35 patients (median age, 59 years; 16 with limited disease and 19 with extensive disease; Eastern Cooperative Oncology Group performance status of < or = 1; median time off treatment 6 weeks) who were previously treated with CDE (n = 33), oral etoposide (n = 2), and reinduction CDE (n = 15); only one patient had received three CDE treatments of five cycles. The CDE regimen was followed by local thoracic radiotherapy in seven patients. Hematologic toxicity of grade 3 or 4, for leukopenia was 27% and 6%, for thrombocytopenia 21% and 13%, and for anemia 17% and 0%, respectively, for a total of 132 cycles. Two patients had neutropenic fever; no toxic death occurred. Nonhematologic toxicity was paresthesia CTC grade 3, diarrhea grade 4, and myalgia grade 3 in one patient each. Reversible paresthesia (CTC grade 1 and 2) in toes and fingers was reported in 69% of patients. Thirty-four patients were assessable for response: complete response in two patients, partial response in 23 patients, stable disease in eight patients, and progressive disease in one patient (response rate, 73.5%; 95% confidence interval, 59% to 88%). One patient was found to have atypical carcinoid at pathologic review and was excluded. Median time to progression was 21 weeks (range, 3 to 40 weeks). Median survival was 31 weeks (range, 6 to 112 weeks). One-year survival was 9%.
Second-line PC in CDE-resistant SCLC patients yields a high response rate and seems non-cross-resistant to CDE. Toxicity was mild in these poor-prognosis patients.
评估紫杉醇联合卡铂（PC）方案对环磷酰胺、阿霉素和依托泊苷（CDE）耐药的小细胞肺癌（SCLC）患者的疗效。
我们对一线接受CDE治疗后3个月内复发的SCLC患者进行了PC方案的II期研究。紫杉醇（175mg/m²，静脉滴注3小时）给药后，每3周进行一次30分钟的卡铂静脉滴注（曲线下面积为7；Chatelut公式），共5个周期。每个周期前常规使用地塞米松、氯马斯汀和雷尼替丁进行预处理。
纳入35例患者（中位年龄59岁；16例为局限期，19例为广泛期；东部肿瘤协作组体能状态评分为≤1；中位治疗中断时间为6周），这些患者既往接受过CDE治疗（n = 33）、口服依托泊苷（n = 2）及再诱导CDE治疗（n = 15）；仅1例患者接受过5个周期中的3个CDE治疗。7例患者在CDE方案后接受了局部胸部放疗。在总共132个周期中，3/4级血液学毒性中，白细胞减少分别为27%和6%，血小板减少分别为21%和13%，贫血分别为17%和0%。2例患者发生中性粒细胞减少性发热；无毒性死亡发生。非血液学毒性方面，1例患者出现3级感觉异常、4级腹泻和3级肌痛。69%的患者报告有趾端和指端可逆性感觉异常（CTC 1/2级）。34例患者可评估疗效：2例完全缓解，23例部分缓解，8例病情稳定，1例病情进展（缓解率73.5%；95%置信区间59%至88%）。1例患者在病理检查时发现为非典型类癌，被排除。中位疾病进展时间为21周（范围3至40周）。中位生存期为31周（范围6至112周）。1年生存率为9%。
对于CDE耐药的SCLC患者，二线PC方案有较高的缓解率，且似乎与CDE无交叉耐药。在这些预后较差的患者中，毒性较轻。
