Department of Clinical Pharmacology and Chemotherapy, N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, 115478, Russia.
Intensive Care Unit, N.N. Blokhin Russian Cancer Research Center, Moscow, Russia.
J Cancer Res Clin Oncol. 2018 Sep;144(9):1817-1823. doi: 10.1007/s00432-018-2695-4. Epub 2018 Jul 5.
Patients with metastatic nonseminomatous germ cell tumors (mNSGCT) and a high tumor burden or a poor performance status at initial diagnosis are at risk from potentially life-threatening early complications during or after the first chemotherapy cycle. The outcomes with dose-reduced first cycle of chemotherapy in this population of patients are not well established.
We performed a retrospective analysis of patients with mNSGCT and International Germ Cell Cancer Collaborative Group (IGCCCG) poor risk features. All patients received cisplatin and etoposide-based combinations as first-line treatment. Ultra high tumor marker levels were defined as α-fetoprotein ≥ 100,000 ng/ml or human chorionic gonadotropin ≥ 200,000 mIU/ml. Before 2005, the first treatment cycle was administered at a full dose in our center. After 2005, we used an abbreviated course of cisplatin and etoposide (EP) for the first cycle, followed by subsequent full-dose administration.
From 1987 to 2012, 265 patients with poor risk features according to IGCCCG received first-line chemotherapy. Among them, 63 out of 265 (24%) patients had ultra high tumor marker levels and/or ECOG performance status of 3-4. Dose reduction of the first chemotherapy cycle was associated with a significant decrease of life-threatening complications from 76 to 44% (p = 0.01), but not with the overall survival (HR 0.99, 95% CI 0.44-2.26).
Dose reduction of the first EP cycle by 40-60% in the subgroup of poor risk patients with ultra high tumor marker levels and/or ECOG performance status 3-4 is associated with significantly lowered acute complication rates but not with overall survival.
在初始诊断时具有高肿瘤负荷或较差表现状态的转移性非精原细胞瘤生殖细胞肿瘤(mNSGCT)患者,在首次化疗周期期间或之后存在潜在危及生命的早期并发症的风险。在这一人群中,剂量减少的首个化疗周期的结果尚未得到充分确立。
我们对具有 mNSGCT 和国际生殖细胞癌协作组(IGCCCG)不良风险特征的患者进行了回顾性分析。所有患者均接受顺铂和依托泊苷为基础的联合治疗作为一线治疗。超高肿瘤标志物水平定义为甲胎蛋白≥100,000ng/ml 或人绒毛膜促性腺激素≥200,000mIU/ml。在 2005 年之前,我们中心在首次治疗周期中给予全剂量治疗。在 2005 年之后,我们在首个周期中使用了缩短疗程的顺铂和依托泊苷(EP),随后给予全剂量治疗。
1987 年至 2012 年,根据 IGCCCG,265 例具有不良风险特征的患者接受了一线化疗。其中,265 例患者中有 63 例(24%)具有超高肿瘤标志物水平和/或 ECOG 表现状态为 3-4。首次化疗周期的剂量减少与危及生命的并发症发生率从 76%显著降低至 44%(p=0.01)相关,但与总生存率无关(HR 0.99,95%CI 0.44-2.26)。
在超高肿瘤标志物水平和/或 ECOG 表现状态为 3-4 的不良风险患者亚组中,EP 首个周期的剂量减少 40-60%与显著降低急性并发症发生率相关,但与总生存率无关。