Gemcitabine alone or with cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic carcinoma - A prospective, randomized phase III study of the Gruppo Oncologico dell'Italia Meridionale
Gemcitabine alone or with cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic carcinoma - A prospective, randomized phase III study of the Gruppo Oncologico dell'Italia Meridionale
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DOI：
10.1002/cncr.10323.abs
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发表时间：
2002-02-15
期刊：
影响因子：
6.2
通讯作者：
Lopez, M
中科院分区：
文献类型：
--
作者：
Colucci, G;Giuliani, F;Lopez, M
背景进行了一项前瞻性、随机III期试验，以确定与吉西他滨（GEM）单药相比，在GEM中添加顺铂（CDDP）是否能够改善晚期胰腺癌患者的疾病进展时间和临床获益率。两组患者的客观缓解率、总生存率和毒性反应模式作为次要终点进行评价。可测量的局部晚期和/或转移性胰腺癌患者。随机接受GEM（A组）或GEM和CDDP联合治疗（B组）。在A组中，每周给予1000 mg/m2 GEM，连续7周，停药2周后，在28天为1周期的第1、8和15天重新开始治疗，共2个周期。在B组中，CDDP的剂量为25 mg/m2/周，在GEM之前1小时给予，剂量与A组相同。在第22天，仅给予GEM。患者在治疗前7周后重新分级，然后在其他2个周期后再次分级。共有107例患者入组试验：54例患者随机分配至A组，53例患者随机分配至B组。A组至疾病进展的中位时间为8周，B组为20周;该差异具有统计学显著性（P = 0.048）。在A组中，基于意向治疗分析记录了1例完全缓解和4例部分缓解，总体缓解率为9.2%（95%置信区间[95%CI]，3-20%）。在Ann B中，无完全缓解，而14例部分缓解，总缓解率为26.4%（95%CI 15-40%）。总体缓解率的差异具有统计学意义（P = 0.02）。肿瘤生长控制率（即，达到完全缓解、部分缓解和疾病稳定的患者总数），A组为42.6%（95%CI，29-57%），Ann B组为56.6%（95%CI，42-70%）。在A组43例患者中的21例（49%）和B组38例患者中的20例（52.6%）中观察到临床获益，无任何显著差异。A组患者的中位总生存期为20周，B组患者为30周（P = 0.43）。两个治疗组的毒性均为轻度，除1-2级虚弱的发生率在统计学上较高外，两组之间无显著差异。Ann B（P = 0.046）结论。与单用GEM相比，GEM + CDDP显著改善了中位疾病进展时间和总体缓解率。两组的临床获益率相似，而B组的中位总生存率更有利，尽管差异未达到统计学显著性。作者得出结论，CDDP和GEM联合治疗目前可被视为局部晚期和/或转移性胰腺腺癌患者的最佳治疗。(C)2002年美国癌症协会。
BACKGROUND. A prospective, randomized Phase III trial was performed to determine whether, compared with gemcitabine (GEM) alone, the addition of cisplatin (CDDP) to GEM was able to improve the time to disease progression and the clinical benefit rate in patients with advanced pancreatic adenocarcinoma. The objective response rate, overall survival rate, and toxicity patterns of patients in the two treatment arms were evaluated as secondary end points.METHODS. Patients with measurable, locally advanced and/or metastatic pancreatic adenocarcinoma. were randomized to receive GEM (Arm A) or a combination of GEM and CDDP (Arm B). In Arm A, a dose of 1000 mg/m(2) GEM per week was administered for 7 consecutive weeks, and, after a 2-week rest, treatment was resumed on Days 1, 8, and 15 of a 28-day cycle for 2 cycles. In Arm B, CDDP was given at a dose of 25 mg/m(2) per week I hour before GEM at the same dose that was used in Arm A. On Day 22, only GEM,,vas administered. Patients were restaged after the first 7 weeks of therapy and then again after the other 2 cycles.RESULTS. A total of 107 patients entered the trial: Fifty-four patients were randomized to Arm A, and 53 patients were randomized to Arm B. The median time to disease progression was 8 weeks in Arm A and 20 weeks in Arm B; this difference was statistically significant (P = 0.048). In Arm A, one complete response and four partial responses were recorded on the basis of an intent-to-treat analysis, with an overall response rate of 9.2% (95% confidence interval [95%CI], 3-20%). In Ann B, there were no complete responses, whereas 14 partial responses were achieved, with an overall response rate of 26.4% (95%CI 15-40%). This difference in the overall response rates was statistically significant (P = 0.02). The tumor growth control rate (i.e., total number of patients who achieved complete responses, partial responses, and stable disease) was 42.6% (95%CI, 29-57%) in Arm A and, 56.6% (95%CI, 42-70%) in Ann B. A clinical benefit was observed in 21 of 43 patients (49%) in Arm A and in 20 of 38 patients (52.6%) in Arm B without any significant difference. The median overall survival was 20 weeks for patients in Arm A and 30 weeks for patients in Arm B (P = 0.43). Toxicity was mild in both treatment arms, with no significant differences between the two groups except for the statistically higher incidence of Grade 1-2 asthenia. in Ann B (P = 0.046)CONCLUSIONS. The addition of CDDP to GEM significantly improved the median time to disease progression and the overall response rate compared with GEM alone. The clinical benefit rate Was similar in both arms, whereas the median overall survival rate was more favorable for Arm B, although the difference did not attain statistical significance. The authors conclude that the combination of CDDP and GEM currently may be considered as an optimal treatment for patients with locally advanced and/or metastatic adenocarcinoma of the pancreas. (C) 2002 American Cancer Society.