Temozolomide in combination with interferon-alfa versus temozolomide alone in patients with advanced metastatic melanoma: A randomized, phase III, multicenter study from the Dermatologic Cooperative Oncology Group
Temozolomide in combination with interferon-alfa versus temozolomide alone in patients with advanced metastatic melanoma: A randomized, phase III, multicenter study from the Dermatologic Cooperative Oncology Group
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DOI：
10.1200/jco.2005.01.1551
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发表时间：
2005-12-10
影响因子：
45.3
通讯作者：
Dummer, R
中科院分区：
文献类型：
--
作者：
Kaufmann, R;Spieth, K;Dummer, R
目的替莫唑胺 (TMZ) 对转移性黑色素瘤的疗效与黑色素瘤标准化疗药物达卡巴嗪 (DTIC) 相同。由于就反应率而言，与干扰素-α (IFN-α) 联合用药似乎优于单药 DTIC，本研究的目的是在一项前瞻性、随机、多中心试验中比较单独使用 TMZ 和 TMZ 加 IFN-α 在客观反应 (OR)、总体生存率和安全性方面的差异。 患者和方法 294 名未经治疗的 IV 期转移性黑色素瘤患者（美国癌症联合委员会分期系统）被随机分配接受单独口服 TMZ 治疗（200 mg/m(2)/天；每 28 天第 1 至 5 天）或与皮下注射 IFN-a（5 MU/m(2)；每周第 1、3 和 5 天）联合使用。 结果 282 名患者符合意向治疗分析条件，其中 271 名患者按照方案接受治疗。在 TMZ + IFN-α 治疗组中，137 名患者中有 33 名（24.1%）对治疗有反应（部分或完全缓解），而在单一治疗组中，134 名患者中有 18 名（13.4%）有明显反应。因此，联合治疗组的缓解率显着更高 (P = .036)。接受 TMZ 治疗的患者的中位生存时间为 8.4 个月（95% CI，7.07 至 9.27），而接受联合治疗的患者的中位生存时间为 9.7 个月（95% CI，8.26 至 11.18；P = 0.16）。 TMZ + IFN-α 组中因血液学毒性而导致的剂量调整和间隔延长的频率明显更高 (P < .001)。 结论 在转移性黑色素瘤中，与单独使用 TMZ 治疗相比，使用 TMZ + IFN-α 治疗的 OR 率显着更高，但这并没有转化为我们研究人群生存期的延长。
PurposeTemozolomide (TMZ) has shown efficacy in metastatic melanoma equal to that of dacarbazine (DTIC), the standard chemotherapeutic agent for melanoma. As the combination with interferon-alfa (IFN-alpha) appears superior to single-agent DTIC regarding response rates, the purpose of this study was to compare TMZ alone and TMZ plus IFN-alpha in terms of objective response (OR), overall survival, and safety in a prospective, randomized, multicenter trial.Patients and MethodsTwo hundred ninety-four patients with untreated stage IV metastatic melanoma (American Joint Committee on Cancer staging system) were randomly assigned to receive either oral TMZ alone (200 mg/m(2)/day; days 1 through 5 every 28 days) or in combination with subcutaneous IFN-a (5 MU/m(2); days 1, 3, and 5 every week).ResultsTwo hundred eighty-two patients were eligible for an intent-to-treat analysis, 271 patients were treated per protocol. In the TMZ + IFN-alpha arm, 33 (24.1 %) of 137 patients responded to therapy (partial or complete remission) whereas in the monotherapy arm, in 18 (13.4%) of 134 patients, a response was evident. Thus, the response rate was significantly higher in the combination arm (P = .036). Median survival time was 8.4 months for patients treated with TMZ (95% CI, 7.07 to 9.27) and 9.7 months for those treated with the combination (95% CI, 8.26 to 11.18; P = .16). Dose modifications and interval prolongations due to hematologic toxicity were significantly more frequent in the TMZ + IFN-alpha arm (P < .001).Conclusion In metastatic melanoma treatment with TMZ + IFN-alpha leads to a significantly superior OR rate compared to treatment with TMZ alone, which did not translate into prolonged survival in our study population.