Lessons learned: NGR-hTNF was safely combined with doxorubicin, showing a promising antitumor activity in unselected patients with relapsed small cell lung cancer.Similar antitumor activity was observed in platinum-sensitive and platinum-resistant patient cohorts.
Background: Relapsed small cell lung cancer (SCLC) patients have limited treatment options and poor outcomes. NGR-hTNF is a vascular-targeting agent, which increases intratumoral chemotherapy penetration and T-lymphocyte infiltration.
Methods: Twenty-eight patients relapsing after at least one platinum-based regimen with a treatment-free interval shorter (n = 16; platinum-resistant) or longer (n = 12; platinum-sensitive) than 3 months received NGR-hTNF 0.8 μg/m2 plus doxorubicin 75 mg/m2 every 3 weeks. The primary endpoint of this single-arm phase II trial was progression-free survival (PFS), and safety, response rate, and survival were secondary endpoints.
Results: The most common grade 3-4 toxicities were neutropenia (53%) and anemia (21%). Median PFS was 3.2 months for all patients, 2.7 months for platinum-resistant patients, and 4.1 months for platinum-sensitive patients. Seven patients had partial responses (25%), including four (25%) with platinum-resistant and three (25%) with platinum-sensitive relapse. Mean changes from baseline in tumor burden (after two, four, and six cycles) did not differ between platinum-resistant (-9%, -29%, and -32%) and platinum-sensitive (-11%, -20%, and -43%) cohorts. Overall survival was associated only with baseline lymphocyte counts, with median survival times of 13.1 and 5.2 months for lymphocyte counts above or below the median, respectively.
Conclusion: NGR-hTNF plus doxorubicin showed manageable toxicity and promising activity in patients with relapsed SCLC.
经验获取
• NGR‐hTNF 与阿霉素合用安全,在对未经选的复发性小细胞肺癌患者用药后表现出抗肿瘤活性,未来可期。
• 铂类药物敏感和铂类药物耐药患者组表现出相似的抗肿瘤活性。
摘要
背景。一直以来,针对复发性小细胞肺癌 (SCLC) 患者的治疗方案都很有限,且疗效不佳。NGR‐hTNF 是一种血管靶向剂,可加强肿瘤内化疗的渗透性和 T 淋巴细胞的浸润。
方法。在至少实施一次基于铂类的给药方案后,有 28 名患者复发,无治疗间隔期短于(n=16;铂类药物耐药)或长于(n=12;铂类药物敏感)3 个月,接受NGR‐hTNF 0.8 μg/m2和阿霉素 75 mg/m2给药,每 3 周一次。此项单臂 II 期试验的主要终点是无进展生存期 (PFS),次要终点是安全性、缓解率和生存率。
结果。3–4 级毒性反应中最常见的是中性粒细胞减少症 (53%) 和贫血(21%)。所有患者的 中位PFS是 3.2 个月,铂类药物耐药患者的中位PFS是 2.7 个月,铂类药物敏感患者的中位PFS是 4.1 个月。7 名患者部分缓解 (25%),包括 4 名 (25%) 铂类药物耐药和 3 名 (25%) 铂类药物敏感的复发患者。铂类药物耐药患者组(−9%、−29% 及 −32%)与铂类药物敏感患者组(−11%、−20% 及 −43%)肿瘤负荷(经过两、四和六个周期后)的基线后平均变化并无差异。总生存期仅与基线淋巴细胞计数相关,淋巴细胞计数高于或低于中位数的患者中位生存期分别为 13.1 和 5.2 个月。
结论。NGR‐hTNF 与阿霉素联合用药的毒性可以控制,且对SCLC患者有抗肿瘤活性,未来可期。
Trial registration: ClinicalTrials.gov NCT00483509.
© AlphaMed Press; the data published online to support this summary is the property of the authors.