Sorafenib has proven efficacy in advanced differentiated thyroid cancer (DTC), but many patients must reduce the dose or discontinue treatment because of toxicity. The tolerability and efficacy of lower starting doses of sorafenib for DTC remain largely unstudied. Methods. We retrospectively examined overall survival, time to treatment failure, time to progression, discontinuation rates, and dose-reduction and interruption rates in patients with metastatic DTC treated with first-line sorafenib outside of a clinical trial. Two patient groups were compared; group 1 received the standard starting dose of 800 mg/day, and group 2 received any dose lower than 800 mg/day. Results. We included 75 adult patients, with 51 in group 1 and 24 in group 2. Mean age at diagnosis was 54 years, and 56% were male. The most common histologies included 43% papillary thyroid cancer of the conventional type, 15% papillary thyroid cancer of the follicular variant, and 15% Hürthle cell carcinoma. Time to treatment failure was 10 months (95% confidence interval [CI]: 5.6-14.3) in group 1 and 8 months (95% CI: 3.4-12.5) in group 2 (p = .56). Median overall survival was 56 months (95% CI: 30.6-81.3) in group 1 and 30 months (95% CI: 16.1-43.8) in group 2 (p = .08). Rates of discontinuation due to disease progression were 79% in group 1 and 91% in group 2, and 21% in group 1 and 9% in group 2 (p = .304) stopped treatment because of toxicity. Dose-reduction rates were 59% and 43% (p = .29), and interruption rates were 65% and 67% (p = .908) in group 1 and group 2, respectively. Conclusion. Efficacy and tolerability of sorafenib in treatment-naïve DTC patients does not appear to be negatively influenced by lower starting daily doses.
摘要
背景 索拉非尼对晚期分化型甲状腺癌 (DTC) 的疗效已获证实,但因其有毒副反应,很多患者不得不减量服用或中止用药。 关于索拉非尼在更低的起始剂量下使用时对 DTC 的疗效和耐受性,目前仍研究甚少。
方法 我们对一些在临床试验之外使用索拉非尼作为一线药物治疗转移性 DTC 的患者进行了一个回顾性分析,评估了他们的总生存期、至治疗失败的时间、至病情进展的时间、中止治疗率、减剂量和中断用药率。 我们共比较了两个患者组;组 1 接受的是 800 mg/天的标准起始剂量,组 2 接受的是低于 800 mg/天的剂量。
结果 我们共纳入了 75 名成人患者,其中组 1 为 51 名,组 2 为 24 名。他们的平均确诊年龄为 54 岁,男性占 56%。 最常见的组织类型包括普通型甲状腺乳头状癌 (占 43%) 、滤泡变异型甲状腺乳头状癌 (占 15%) 和 Hürthle 细胞癌 (占 15%) 。 组 1 的至治疗失败的时间为 10 个月 (95% 置信区间 [CI]: 5.6-14.3) ,组 2 为 8 个月 (95% CI: 3.4–12.5) (p = 0.56)。 组 1 的中位总生存期为 56 个月 (95% CI: 30.6–81.3),组 2 为 30 个月 (95% CI: 16.1–43.8) (p = 0.08)。 因疾病进展而导致的中止治疗率在组 1 中为 79%,在组 2 中为 91%;因毒性作用而导致的停止治疗率在组 1 中为 21%,在组 2 中为 9% (p = 0.304)。 组 1 和组 2 的减剂量率分别为 59% 和 43% (p = 0.29),用药中断率分别为 65% 和 67% (p = 0.908)。
结论 下调索拉非尼的日起始剂量对其在未获治疗的 DTC 患者中的疗效和耐受性似乎并不会造成负面影响。The Oncologist 2014;19:477–482
Keywords: Adverse events; Dose reduction; Drug interruptions; Overall survival; Time to failure.