Miolo Gianmaria, Buonadonna Angela, Lombardi Davide, Scalone Simona, Lauretta Andrea, Della Puppa Lara, Corona Giuseppe
Medical Oncology and Cancer Prevention Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy.
Unit of General Oncologic Surgery, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy.
Front Oncol. 2024 Jul 25;14:1437732. doi: 10.3389/fonc.2024.1437732. eCollection 2024.
In the landscape of metastatic soft tissue sarcoma (mSTS) treatment, anthracyclines have shown efficacy; however, their associated toxicity imposes significant limitations, especially in frail elderly patients with mSTS who are highly susceptible to severe adverse effects. In this context, trabectedin, due to its distinct pharmacological profile and safety profile, may represent an interesting alternative being demonstrated to be active in treating mSTS. These features hold particular significance for elderly and unfit patients with mSTS, where balancing treatment benefits with potential adverse effects represents the pivotal objective.
The investigation was focused on a specific group of 11 elderly patients with mSTS aged ≥70, all undergoing first-line treatment with trabectedin, and it was supported by comprehensive pharmacokinetic and pharmacodynamic studies. Among these patients, 9 out of 11 started the treatment at a dose of 1.5 mg/m.
The primary objective of this investigation is to highlight trabectedin as a valuable first-line treatment option for elderly and unfit patients with mSTS. Additionally, this investigation seeks to explore whether higher administered doses of trabectedin can enhance clinical outcomes while maintaining the same toxicity profiles. The median progression-free survival (PFS) was 77 days (95% CI, 53-89), the median overall survival (OS) was 397 days (95% CI, 66-2,102), while the overall toxicity of grade 3-4 severity amounted to 43%.
These findings provide new insights into the clinical outcomes and toxicity associated with trabectedin in an elderly patient population, enhancing our understanding of better treatment approaches for a specific population of patients with mSTS.
在转移性软组织肉瘤（mSTS）的治疗领域，蒽环类药物已显示出疗效；然而，其相关毒性带来了重大限制，尤其是在对严重不良反应高度敏感的老年体弱mSTS患者中。在此背景下，曲贝替定因其独特的药理学特征和安全性特征，可能是一种有吸引力的替代药物，已被证明在治疗mSTS中具有活性。这些特征对于老年和身体状况不佳的mSTS患者尤为重要，在这类患者中，平衡治疗益处与潜在不良反应是关键目标。
该研究聚焦于11名年龄≥70岁的老年mSTS患者的特定群体，所有患者均接受曲贝替定一线治疗，并得到了全面的药代动力学和药效学研究的支持。在这些患者中，11人中有9人开始以1.5mg/m²的剂量进行治疗。
本研究的主要目的是强调曲贝替定是老年和身体状况不佳的mSTS患者有价值的一线治疗选择。此外，本研究旨在探讨更高剂量的曲贝替定是否能在保持相同毒性特征的同时提高临床疗效。中位无进展生存期（PFS）为77天（95%CI，53 - 89），中位总生存期（OS）为397天（95%CI，66 - 2102），而3 - 4级严重程度的总体毒性为43%。
这些发现为老年患者群体中曲贝替定的临床疗效和毒性提供了新的见解，增强了我们对特定mSTS患者群体更好治疗方法的理解。
