PACLITAXEL AND CARBOPLATIN IN COMBINATION IN THE TREATMENT OF ADVANCED NON-SMALL-CELL LUNG-CANCER - A PHASE-II TOXICITY, RESPONSE, AND SURVIVAL ANALYSIS
PACLITAXEL AND CARBOPLATIN IN COMBINATION IN THE TREATMENT OF ADVANCED NON-SMALL-CELL LUNG-CANCER - A PHASE-II TOXICITY, RESPONSE, AND SURVIVAL ANALYSIS
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DOI：
10.1200/jco.1995.13.8.1860
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发表时间：
1995-08-01
影响因子：
45.3
通讯作者：
OZOLS, RF
中科院分区：
文献类型：
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作者：
LANGER, CJ;LEIGHTON, JC;OZOLS, RF
目的：确定紫杉醇联合用药的活性和毒性（24小时）和卡铂在晚期非小细胞肺癌（NSCLC）中的应用。合格性要求可测量疾病（IV期或IIB期伴恶性胸腔积液），东部肿瘤协作组（ECOG）体力状态为0或1，中性粒细胞绝对计数大于或等于2，000/μ L，血小板计数大于或等于100，000/μ L，血清肌酐浓度小于或等于1.5 mg/dL，胆红素水平小于或等于2 mg/dL。紫杉醇最初以135 mg/m（2）/d的剂量给药，然后在第2天使用Calvert公式在浓度-时间曲线下目标面积（AUG）为7.5处给予卡铂。在第二个周期和后续周期中，在第3 - 17天皮下（SC）给予粒细胞集落刺激因子（G-CSF）5 μ g/kg。在持续低于4级骨髓抑制的患者中，紫杉醇剂量依次递增，每周期40 mg/m2，最高达215 mg/m2。治疗重复在3周的时间间隔为6 cycles.Results：从1993年6月至1994年2月，54例患者入组，53是可评估的毒性和反应。中位年龄为62岁（范围：34 - 84岁）。69%为男性，65%患有腺癌，93%患有IV期疾病。进行了268个周期的治疗; 32例患者（59%）完成了所有6个周期。20例患者（37%）在治疗期间发生了25例非预期住院（占周期的9.3%）。骨髓抑制是主要毒性;第一个周期后57%的患者发生3级或4级粒细胞减少症，但在引入G-CSP后的第二个周期中降至35%，并在随后的周期中始终保持小于或等于22%。在第一个周期内发生了7次血小板减少性发热。分别有47%和33%的患者发生3级或4级血小板减少和贫血。8名患者（15%）需要血小板输注，16名（30%）需要浓缩红细胞支持。神经病变、疼痛/关节痛和血小板减少症，尽管通常为轻度，但具有累积性。接受3个或3个以上周期治疗的患者中，紫杉醇剂量增至215 mg/m2的比例大于或等于70%。当AUC为7.5时，第一周期卡铂的中位剂量为424 mg/m（2）（范围，273至709 mg/m（2））。客观缓解率为62%，其中5例（9%）完全缓解，28例（53%）部分缓解。中位无进展生存期为28周，中位生存期为53周。1年生存率为54%。结论：紫杉醇联合卡铂治疗晚期非小细胞肺癌有效，可提高生存率，值得在III期临床试验中进一步研究。J Clin Oncol 13：1860-1870。(C)1995年，美国临床肿瘤学会。
Purpose: To determine the activity and toxicity of combination paclitaxel (24 hours) and carboplatin in advanced non-small-cell lung cancer (NSCLC).Patients and Methods: Eligibility required measurable disease (stage IV or stage IIB with malignant pleural effusion), Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, absolute neutrophil count greater than or equal to 2,000/mu L, platelet count greater than or equal to 100,000/mu L serum creatinine concentration less than or equal to 1.5 mg/dL, and bilirubin level less than or equal to 2 mg/dL. Paclitaxel was initially administered at a dose of 135 mg/m(2)/d, followed by carboplatin on day 2 at a targeted area under the concentration-time curve (AUG) of 7.5 using the Calvert formula. Granulocyte colony-stimulating factor (G-CSF) 5 mu g/kg subcutaneously (SC) on days 3 to 17 was introduced during the second and subsequent cycles. In patients who sustained less than grade 4 myelosuppression, the paclitaxel dose was sequentially escalated 40 mg/m(2) per cycle to a maximum of 215 mg/m(2). Treatment was repeated at 3-week intervals for six cycles.Results: From June 1993 through February 1994, 54 patients were enrolled; 53 are assessable for toxicity and response. The median age was 62 years (range, 34 to 84). Sixty-nine percent were male, 65% had adenocarcinoma, and 93% had stage IV disease. Two hundred sixty-eight cycles were administered; 32 patients (59%) completed all six cycles. Twenty-five unanticipated hospitalizations occurred during treatment (9.3% of cycles) in 20 patients (37%). Myelosuppression was the principal toxicity; grade 3 or 4 granulocytopenia occurred in 57% of patients after the first cycle, but decreased to 35% during the second cycle after introduction of G-CSP and consistently remained less than or equal to 22% during subsequent cycles. Seven episodes of neutropenic fever occurred, all during the first cycle. Grade 3 or 4 thrombocytopenia and anemia occurred in 47% and 33% of patients, respectively. Eight patients (15%) required platelet transfusions and 16(30%) required packed RBC support. Neuropathy, my algias/arthralgias, and thrombocytopenia, although generally mild, were cumulative. The paclitaxel dose wets boosted to 215 mg/m(2) in greater than or equal to 70% of patients who received three or more cycles. Ar an AUC of 7.5, the median first-cycle carboplatin dose was 424 mg/m(2) (range, 273 to 709 mg/m(2)). The objective response rate was 62%, with five (9%) complete responses and 28 (53%) partial responses. The median progression-free survival time was 28 weeks and the median survival time 53 weeks. The 1-year survival rate is 54%.Conclusion: The paclitaxel-carboplatin combination is active in advanced NSCLC and may enhance survival; it merits further investigation in phase III trials.J Clin Oncol 13:1860-1870. (C) 1995 by American Society of Clinical Oncology.