Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma
Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma
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DOI：
10.1200/jco.2000.18.1.158
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发表时间：
2000-01-01
影响因子：
45.3
通讯作者：
Thatcher, N
中科院分区：
文献类型：
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作者：
Middleton, MR;Grob, JJ;Thatcher, N
目的：在305例晚期转移性黑色素瘤患者中，比较替莫唑胺和达卡巴嗪（DTIC）的总生存期、无进展生存期（PFS）、客观缓解和安全性，并评估两种药物及其代谢产物的健康相关生活质量（QOL）和药代动力学，（3-甲基三氮烯-1-基）咪唑-4-甲酰亚胺（MTIC），患者和方法：患者随机接受口服替莫唑胺，起始剂量为200 mg/m2/d，每28天一次，持续5天，或静脉注射DTIC，起始剂量为250 mg/m2（2）/天，每21天治疗5天。结果：在意向治疗人群中，接受替莫唑胺治疗的患者的中位生存时间为7.7个月，接受DTIC治疗的患者的中位生存时间为6.4个月（风险比，1.18; 95%置信区间[CI]，0.92至1.52）。替莫唑胺治疗组的中位PFS时间（1.9个月）显著长于DTIC治疗组（1.5个月）（P = 0.012;风险比，1.37; 95% CI，1.07 - 1.75）。未观察到药物安全性的重大差异。替莫唑胺耐受性良好，在28天周期后期产生非累积性、一过性骨髓抑制。最常见的非血液学毒性为轻度至中度恶心和呕吐，易于管理，替莫唑胺治疗改善了健康相关QOL;更多患者在第12周时显示出身体功能改善或维持。口服替莫唑胺治疗后母体药物和活性代谢产物MTIC的全身暴露量（曲线下面积）高于DTIC IV给药后。结论：替莫唑胺的疗效与DTIC相当，是晚期转移性黑色素瘤患者的口服替代药物。(C)2000年，美国临床肿瘤学会。
Purpose: To compare, in 305 patients with advanced metastatic melanoma, temozolomide and dacarbazine (DTIC) in terms of overall survival, progression-free survival (PFS), objective response, and safety, and to assess health-related quality of life (QOL) and pharmacokinetics of both drugs and their metabolite, 5-(3-methyltriazen-1-yl)imidazole-4-carboximide (MTIC),Patients and Methods: Patients were randomized to receive either oral temozolamide at a starting dosage of 200 mg/m(2)/d for 5 days every 28 days or intravenous (IV) DTIC at a starting dosage of 250 mg/m(2)/d for 5 days every 21 days.Results: In the intent-to-treat population, median survival time was 7.7 months for patients treated with temozolomide and 6.4 months for those treated with DTIC (hazards ratio, 1.18; 95% confidence interval [CI], 0.92 to 1.52). Median PFS time was significantly longer in the temozolomide-treated group(1.9 months) than in the DTIC-treated group (1.5 months) (P = .012; hazards ratio, 1.37; 95% CI, 1.07 to 1.75). No major difference in drug safety was observed. Temozolomide was well tolerated and produced a noncumulative, transient myelosuppression late in the 28-day cycle. The most common nonhematologic toxicities were mild to moderate nausea and vomiting, which were easily managed, Temozolomide therapy improved health-related QOL; more patients showed improvement or maintenance of physical functioning at week 12. Systemic exposure (area under the curve) to the parent drug and the active metabolite, MTIC, was higher after treatment with oral temozolamide than after IV administration of DTIC,Conclusion: Temozolomide demonstrates efficacy equal to that of DTIC and is an oral alternative for patients with advanced metastatic melanoma. (C) 2000 by American Society of Clinical Oncology.