新辅助化疗与初始肿瘤细胞减灭术用于 IIIC 或 IV 期卵巢癌。

Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer.

机构信息

University Hospitals, K.U. Leuven Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Herestraat 49, B-3000 Leuven, Belgium.

出版信息

N Engl J Med. 2010 Sep 2;363(10):943-53. doi: 10.1056/NEJMoa0908806.

DOI:10.1056/NEJMoa0908806

PMID:20818904

Abstract

BACKGROUND

Primary debulking surgery before initiation of chemotherapy has been the standard of care for patients with advanced ovarian cancer.

METHODS

We randomly assigned patients with stage IIIC or IV epithelial ovarian carcinoma, fallopian-tube carcinoma, or primary peritoneal carcinoma to primary debulking surgery followed by platinum-based chemotherapy or to neoadjuvant platinum-based chemotherapy followed by debulking surgery (so-called interval debulking surgery).

RESULTS

Of the 670 patients randomly assigned to a study treatment, 632 (94.3%) were eligible and started the treatment. The majority of these patients had extensive stage IIIC or IV disease at primary debulking surgery (metastatic lesions that were larger than 5 cm in diameter in 74.5% of patients and larger than 10 cm in 61.6%). The largest residual tumor was 1 cm or less in diameter in 41.6% of patients after primary debulking and in 80.6% of patients after interval debulking. Postoperative rates of adverse effects and mortality tended to be higher after primary debulking than after interval debulking. The hazard ratio for death (intention-to-treat analysis) in the group assigned to neoadjuvant chemotherapy followed by interval debulking, as compared with the group assigned to primary debulking surgery followed by chemotherapy, was 0.98 (90% confidence interval [CI], 0.84 to 1.13; P=0.01 for noninferiority), and the hazard ratio for progressive disease was 1.01 (90% CI, 0.89 to 1.15). Complete resection of all macroscopic disease (at primary or interval surgery) was the strongest independent variable in predicting overall survival.

CONCLUSIONS

Neoadjuvant chemotherapy followed by interval debulking surgery was not inferior to primary debulking surgery followed by chemotherapy as a treatment option for patients with bulky stage IIIC or IV ovarian carcinoma in this study. Complete resection of all macroscopic disease, whether performed as primary treatment or after neoadjuvant chemotherapy, remains the objective whenever cytoreductive surgery is performed. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00003636.)

摘要

背景

在开始化疗之前进行初次肿瘤细胞减灭术一直是晚期卵巢癌患者的标准治疗方法。

方法

我们将 IIIC 期或 IV 期上皮性卵巢癌、输卵管癌或原发性腹膜癌患者随机分配至先行初次肿瘤细胞减灭术然后接受铂类为基础的化疗，或先行新辅助铂类化疗然后接受肿瘤细胞减灭术（所谓的间隔肿瘤细胞减灭术）。

结果

在随机分配至研究治疗的 670 例患者中，有 632 例（94.3%）符合条件并开始接受治疗。这些患者中大多数在初次肿瘤细胞减灭术时有广泛的 IIIC 期或 IV 期疾病（转移灶的直径大于 5 厘米者占 74.5%，大于 10 厘米者占 61.6%）。初次肿瘤细胞减灭术后，最大残余肿瘤直径为 1 厘米或更小者占 41.6%，间隔肿瘤细胞减灭术后占 80.6%。与初次肿瘤细胞减灭术相比，间隔肿瘤细胞减灭术后术后不良事件和死亡率的发生率往往更高。与初次肿瘤细胞减灭术后继以化疗相比，新辅助化疗后继以间隔肿瘤细胞减灭术的死亡风险比（意向治疗分析）为 0.98（90%置信区间，0.84 至 1.13；非劣效性检验 P=0.01），疾病进展风险比为 1.01（90%置信区间，0.89 至 1.15）。所有宏观疾病（初次或间隔手术时）的完全切除是预测总生存期的最强独立变量。

结论

在这项研究中，对于体积较大的 IIIC 期或 IV 期卵巢癌患者，新辅助化疗继以间隔肿瘤细胞减灭术与初次肿瘤细胞减灭术继以化疗作为治疗选择相比并不差。只要进行细胞减灭术，无论作为初始治疗还是新辅助化疗后，完全切除所有宏观疾病仍然是目标。（由美国国家癌症研究所资助；ClinicalTrials.gov 编号，NCT00003636。）