Medical Oncology Department, Instituto Nacional de Cancerología de México(INCan), San Fernando N22 Colonia Sección XVI, Tlalpan Mexico City, Mexico.
Radiat Oncol. 2013 Sep 8;8:209. doi: 10.1186/1748-717X-8-209.
Chloroquine (CLQ), an antimalarial drug, has a lysosomotropic effect associated with increased radiationsensibility, which is mediated by the leakage of hydrolytic enzymes, increased apoptosis, autophagy and increased oxidative stress in vitro. In this phase II study, we evaluated the efficacy and safety of radiosensibilization using CLQ concomitant with 30 Gray (Gy) of whole-brain irradiation (WBI) to treat patients with brain metastases (BM) from solid tumors.
Seventy-three eligible patients were randomized. Thirty-nine patients received WBI (30 Gy in 10 fractions over 2 weeks) concomitant with 150 mg of CLQ for 4 weeks (the CLQ arm). Thirty-four patients received the same schedule of WBI concomitant with a placebo for 4 weeks (the control arm). All the patients were evaluated for quality of life (QoL) using the EORTC Quality of Life (QoL) Questionnaire (EORTC QLQ-C30) (Mexican version) before beginning radiotherapy and one month later.
The overall response rate (ORR) was 54% for the CLQ arm and 55% for the control arm (p=0.92). The progression-free survival of brain metastases (BMPFS) rates at one year were 83.9% (95% CI 69.4-98.4) for the CLQ arm and 55.1% (95% CI 33.6-77.6) for the control arm. Treatment with CLQ was independently associated with increased BMPFS (RR 0.31,95% CI [0.1-0.9], p=0.046).The only factor that was independently associated with increased overall survival (OS) was the presence of< 4 brain metastases (RR 1.9, 95% CI [1.12-3.3], p=0.017). WBI was associated with improvements in cognitive and emotional function but also with worsened nausea in both patients groups. No differences in QoL or toxicity were found between the study arms.
Treatment with CLQ plus WBI improved the control of BM (compared with the control arm) with no increase in toxicity; however, CLQ did not improve the RR or OS. A phase III clinical trial is warranted to confirm these findings.
氯喹（CLQ）是一种抗疟药物，具有溶酶体趋向性，与水解酶的漏出、增加的细胞凋亡、自噬和体外增加的氧化应激有关。在这项 II 期研究中，我们评估了使用 CLQ 进行放射增敏联合全脑照射（WBI）治疗实体瘤脑转移（BM）患者的疗效和安全性。
共纳入 73 例符合条件的患者进行随机分组。39 例患者接受 WBI（2 周内 10 次分割，每次 30 Gy）联合 4 周的 150mg CLQ（CLQ 组）。34 例患者接受相同方案的 WBI 联合 4 周安慰剂（对照组）。所有患者在开始放疗前和放疗后 1 个月使用 EORTC 生活质量问卷（EORTC QLQ-C30）（墨西哥语版）评估生活质量（QoL）。
CLQ 组的总缓解率（ORR）为 54%，对照组为 55%（p=0.92）。CLQ 组的 1 年脑转移进展无进展生存率（BMPFS）为 83.9%（95%CI 69.4-98.4），对照组为 55.1%（95%CI 33.6-77.6）。CLQ 治疗与增加的 BMPFS 独立相关（RR 0.31，95%CI [0.1-0.9]，p=0.046）。唯一与总生存（OS）增加相关的因素是脑转移灶数<4（RR 1.9，95%CI [1.12-3.3]，p=0.017）。WBI 可改善认知和情绪功能，但也会引起两组患者的恶心加重。两组间 QoL 或毒性无差异。
CLQ 联合 WBI 治疗可改善 BM 控制（与对照组相比），但不增加毒性；然而，CLQ 并未改善 RR 或 OS。需要进行 III 期临床试验以证实这些发现。
