Department of Maternal and Child Health and Urological Sciences, University "Sapienza", Policlinico "Umberto I" Rome, Italy.
Department of Maternal and Child Health and Urological Sciences, University "Sapienza", Policlinico "Umberto I" Rome, Italy.
Gynecol Oncol. 2019 Jul;154(1):138-143. doi: 10.1016/j.ygyno.2019.04.009. Epub 2019 May 9.
To evaluate hematologic adverse effect profiles associated with frontline platinum-based chemotherapy in ovarian cancer patients according to BRCA 1/2 mutational status.
Patients with high-grade serous ovarian cancer and a known BRCA mutational status who received in frontline 6 cycles of Carboplatin (AUC 5) plus Paclitaxel 175 mg/mq were retrospectively selected from our databases. Hematologic toxicity profiles of BRCA mutated patients were compared to non-mutated patients, according to EORTC Common Terminology Criteria for Adverse Events (CTCAE_4.02).
Totally, 176 women of whom 58 (33%) were BRCA1/2 mutation carriers - 40 BRCA1 (69%) and 18 (31%) BRCA2 mutations carriers - and 118 (67%) non-carriers were identified. A significant higher frequency of thrombocytopenia (24% vs 5%; p < 0.001), anemia (21% vs 7%; p = 0.006) and neutropenia (62% vs 27%; p ≤0.001) was observed in BRCA mutated patients, resulting in a higher percentage of granulocyte-colony stimulating growth factors injection (12% versus 1%, p < 0.001) and dose delay (19% versus 27%, p = 0.005). The multivariate analysis confirmed that granulocyte-colony stimulating growth factors injection and dose delay were statistically significantly more frequent in BRCA mutated patients (OR 2.567, 95% CI 1.136-5.798, p = 0.035; OR 3.860, 95% CI 1.098-13.570, p = 0.023). Finally, the total number of hematologic adverse events compared between the two groups of patients during the entire treatment period showed a substantial higher rate of hematologic adverse events in BRCA mutated population.
Germline BRCA 1/2 mutations are associated with a higher hematologic toxicity in patients with ovarian cancer who underwent platinum-based chemotherapy.
根据 BRCA1/2 突变状态，评估卵巢癌患者一线铂类化疗相关的血液学不良事件谱。
从我们的数据库中回顾性选择了接受一线 6 个周期卡铂（AUC 5）加紫杉醇 175mg/mq 的高级别浆液性卵巢癌且已知 BRCA 突变状态的患者。根据 EORTC 不良事件通用术语标准（CTCAE_4.02），比较 BRCA 突变患者和非突变患者的血液学毒性谱。
总共 176 名女性，其中 58 名（33%）为 BRCA1/2 突变携带者-40 名 BRCA1（69%）和 18 名（31%）BRCA2 突变携带者，118 名（67%）为非携带者。BRCA 突变患者血小板减少症（24%比 5%；p<0.001）、贫血（21%比 7%；p=0.006）和中性粒细胞减少症（62%比 27%；p≤0.001）的发生率显著更高，导致粒细胞集落刺激因子注射（12%比 1%；p<0.001）和剂量延迟（19%比 27%；p=0.005）的比例更高。多变量分析证实，BRCA 突变患者粒细胞集落刺激因子注射和剂量延迟的发生率明显更高（OR 2.567，95%CI 1.136-5.798，p=0.035；OR 3.860，95%CI 1.098-13.570，p=0.023）。最后，比较两组患者在整个治疗期间的血液学不良事件总数，BRCA 突变组的血液学不良事件发生率明显更高。
卵巢癌患者接受铂类化疗时，种系 BRCA1/2 突变与更高的血液学毒性相关。
