一项随机II期研究，比较每8小时给药一次或每日给药一次替莫唑胺联合干扰素α-2b或沙利度胺治疗转移性恶性黑色素瘤的疗效。

Randomized phase II study of temozolomide given every 8 hours or daily with either interferon alfa-2b or thalidomide in metastatic malignant melanoma.

作者信息

Danson S, Lorigan P, Arance A, Clamp A, Ranson M, Hodgetts J, Lomax L, Ashcroft L, Thatcher N, Middleton M R

机构信息

Christie Hospital, Manchester, United Kingdom.

出版信息

J Clin Oncol. 2003 Jul 1;21(13):2551-7. doi: 10.1200/JCO.2003.10.039.

DOI:10.1200/JCO.2003.10.039

PMID:12829675

Abstract

PURPOSE

Temozolomide is an imidazotetrazine with a mechanism of action similar to dacarbazine and equivalent activity in melanoma. It is well tolerated and is a candidate for combination chemotherapy and schedule manipulation. In this study, we combined temozolomide with interferon alfa-2b and, separately, with thalidomide, and we administered temozolomide alone in a compressed schedule. The objectives of this randomized phase II, two-center study were to determine response rates, overall survival, and tolerability of the regimens in patients with advanced metastatic melanoma.

PATIENTS AND METHODS

One hundred eighty-one patients with metastatic melanoma were randomly assigned to receive up to six 4-weekly cycles consisting of temozolomide 200 mg/m2 every 8 hours for five doses, or temozolomide 200 mg/m2 daily for days 1 to 5 plus interferon alfa-2b 5 MU (million International Units) subcutaneously three times a week, or temozolomide 150 mg/m2 (increased after one cycle to 200 mg/m2) daily on days 1 to 5 plus thalidomide 100 mg daily days 1 to 28.

RESULTS

The treatment arms were well balanced for known prognostic factors. Median survival was 5.3 months for 8-hourly temozolomide, 7.7 months for temozolomide/interferon, and 7.3 months for temozolomide/thalidomide; and 1-year survivals were 18%, 26%, and 24%, respectively. Response or disease stabilization occurred in 20% of patients (95% confidence interval [CI], 10% to 33%) given 8-hourly temozolomide, 21% (95% CI, 12% to 33%) given temozolomide/interferon, and 25% (95% CI, 15% to 38%) given temozolomide/thalidomide. Grade 3 or 4 nonhematologic toxicities were similar in each arm except for infection, which was more frequent with 8-hourly temozolomide. There were fewer instances of grade 3 or 4 myelotoxicity with temozolomide/thalidomide.

CONCLUSION

Of the three regimens tested, the combination of temozolomide and thalidomide seems the most promising for future study.

摘要

目的

替莫唑胺是一种咪唑并四嗪，其作用机制与达卡巴嗪相似，在黑色素瘤中具有同等活性。它耐受性良好，是联合化疗和给药方案调整的候选药物。在本研究中，我们将替莫唑胺与干扰素α-2b联合使用，另外还将其与沙利度胺联合使用，并以紧凑的给药方案单独使用替莫唑胺。这项随机II期双中心研究的目的是确定晚期转移性黑色素瘤患者中这些治疗方案的缓解率、总生存期和耐受性。

患者与方法

181例转移性黑色素瘤患者被随机分配接受最多六个为期4周的周期治疗，治疗方案包括：每8小时一次，每次200mg/m²，共五剂的替莫唑胺；或第1至5天每天200mg/m²的替莫唑胺加每周三次皮下注射5MU（百万国际单位）的干扰素α-2b；或第1至5天每天150mg/m²（一个周期后增至200mg/m²）的替莫唑胺加第1至28天每天100mg的沙利度胺。

结果

各治疗组在已知预后因素方面均衡良好。每8小时一次给药的替莫唑胺组中位生存期为5.3个月，替莫唑胺/干扰素组为7.7个月，替莫唑胺/沙利度胺组为7.3个月；1年生存率分别为18%、26%和24%。每8小时一次给药的替莫唑胺组中20%的患者（95%置信区间[CI]，10%至33%）出现缓解或疾病稳定，替莫唑胺/干扰素组为21%（95%CI,12%至33%），替莫唑胺/沙利度胺组为25%（95%CI,15%至38%）。除感染外，各治疗组3级或4级非血液学毒性相似，感染在每8小时一次给药的替莫唑胺组中更常见。替莫唑胺/沙利度胺组3级或4级骨髓毒性病例较少。