吉西他滨联合顺铂与单药吉西他滨一线治疗晚期胰腺癌的随机 III 期临床试验：GIP-1 研究。

Randomized phase III trial of gemcitabine plus cisplatin compared with single-agent gemcitabine as first-line treatment of patients with advanced pancreatic cancer: the GIP-1 study.

机构信息

Medical and Experimental Oncology Unit, Oncology Institute Giovanni Paolo II, Bari, Italy.

出版信息

J Clin Oncol. 2010 Apr 1;28(10):1645-51. doi: 10.1200/JCO.2009.25.4433. Epub 2010 Mar 1.

DOI:10.1200/JCO.2009.25.4433

PMID:20194854

Abstract

PURPOSE

Single-agent gemcitabine became standard first-line treatment for advanced pancreatic cancer after demonstration of superiority compared with fluorouracil. The Gruppo Italiano Pancreas 1 randomized phase III trial aimed to compare gemcitabine plus cisplatin versus gemcitabine alone (ClinicalTrials.gov ID NCT00813696).

PATIENTS AND METHODS

Patients with locally advanced or metastatic pancreatic cancer, age 18 to 75 years, and Karnofsky performance status (KPS) > or = 50, were randomly assigned to receive gemcitabine (arm A) or gemcitabine plus cisplatin (arm B). Arm A: gemcitabine 1,000 mg/m(2) weekly for 7 weeks, and, after a 1-week rest, on days 1, 8, and 15 every 4 weeks. Arm B: cisplatin 25 mg/m(2) added weekly to gemcitabine, except cycle 1 day 22. Primary end point was overall survival. To have 8% power of detecting a 0.74 hazard ratio (HR) of death, with bilateral alpha .05, 355 events were needed and 400 patients planned.

RESULTS

Four hundred patients were enrolled (arm A: 199; arm B: 201). Median age was 63, 59% were male, 84% had stage IV, and 83% had KPS > or = 80. Median overall survival was 8.3 months versus 7.2 months in arm A and B, respectively (HR, 1.10; 95% CI, 0.89 to 1.35; P = .38). Median progression-free survival was 3.9 months versus 3.8 months in arm A and B, respectively (HR, 0.97; 95% CI, 0.80 to 1.19; P = .80). The objective response rate was 10.1% in A and 12.9% in B (P = .37). Clinical benefit was experienced by 23.0% in A and 15.1% in B (P = .057). Combination therapy produced more hematologic toxicity, without relevant differences in nonhematologic toxicity.

CONCLUSION

The addition of weekly cisplatin to gemcitabine failed to demonstrate any improvement as first-line treatment of advanced pancreatic cancer.

摘要

目的

与氟尿嘧啶相比，单药吉西他滨在晚期胰腺癌中的疗效优势使其成为标准的一线治疗药物。意大利胰腺研究组 1 期随机 III 期临床试验旨在比较吉西他滨联合顺铂与吉西他滨单药治疗（ClinicalTrials.gov ID NCT00813696）。

患者和方法

局部晚期或转移性胰腺癌患者，年龄 18 至 75 岁，Karnofsky 体能状态（KPS）≥50%，随机分配接受吉西他滨（A 组）或吉西他滨加顺铂（B 组）治疗。A 组：吉西他滨 1000mg/m²，每周 7 天，1 周休息后，每 4 周第 1、8、15 天给药。B 组：吉西他滨每周加用顺铂 25mg/m²，除第 1 周期第 22 天外。主要终点是总生存期。为了以 8%的概率检测出死亡风险 0.74 的 0.8 危险比（HR），双侧α.05，需要 355 个事件和 400 例患者。

结果

共入组 400 例患者（A 组 199 例，B 组 201 例）。中位年龄为 63 岁，59%为男性，84%为 IV 期，83%的 KPS≥80%。A 组和 B 组的中位总生存期分别为 8.3 个月和 7.2 个月（HR，1.10；95%CI，0.89 至 1.35；P=0.38）。中位无进展生存期分别为 A 组 3.9 个月和 B 组 3.8 个月（HR，0.97；95%CI，0.80 至 1.19；P=0.80）。A 组客观缓解率为 10.1%，B 组为 12.9%（P=0.37）。A 组临床获益率为 23.0%，B 组为 15.1%（P=0.057）。联合治疗组血液学毒性增加，但非血液学毒性无明显差异。