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丝裂霉素-C与吉西他滨联合用于局部晚期/转移性胰腺癌的局部区域/全身化疗及同时采用影像学方法和肿瘤标志物进行随访。

Locoregional/systemic chemotherapy of locally advanced/metastasized pancreatic cancer with a combination of mitomycin-C and gemcitabine and simultaneous follow-up by imaging methods and tumor markers.

作者信息

Klapdor R, Seutter E, Lang-Pölckow E M, Reichle H, Hinrichs A

机构信息

Jerusalem Hospital, Hamburg, Germany.

出版信息

Anticancer Res. 1999 Jul-Aug;19(4A):2459-69.

Abstract

Stimulated by surprising results in the first 7 patients treated with intraarterial/systemic chemotherapy with a combination of Mitomycin-C + Gemcitabine we now report on the data of 28 pancreatic cancer patients in comparison to 15 patients treated with gemcitabine alone(1000 mg/m2). Tumor response was evaluated on the basis of imaging methods, tumor markers and life quality parameters like body weight, pains and Karnofsky index etc. Tumor markers were monthly determined, imaging methods every 1-3 months. The locoregional/systemic approach included 3 week cycles with i.a. application of mitomycin-C + gemcitabine on day 1 and i.v. application of gemcitabine on days 8 and 15. The alltogether 125 cycles (mean 4 cycles per patient) resulted in 43% PR (n = 12), 1 CR (3%), 255 MR, 11% SD and 18% PD in the imaging methods and 20% CR, 60% PR, 4% MR and 12% SD in the course of the relevant tumor markers. Progression free survival amounted to a median of 7.5 (6) months defined by imaging methods (tumor markers). Second line treatments following new progress after effective locoregional approach with gemcitabine or a combination of gemcitabine + oxaliplatin did not result in a new tumor regression. However, third line therapy trials in 3 patients with high dose 5-FU or CPT 11 induced new antitumoral efficacy (survival of these tumors > 15, > 17 and > 28 months, n = 2 M1, n = 1 T3M0). About 75% of patients reported on a relevant benefit of life quality parameters. Side effects are on principle comparable to those of gemcitabine monotherapy, except for a tendency to a higher rate of pulmonary complications and 1 HUS observed. Even if not compared in a randomized study locoregional/systemic combined treatment modality seems to result in a higher rate of abjective tumor response defined by imaging methods as well as tumormarkers. Comparing tumor marker and imaging response to therapy CA 19-9 often showed a more rapid and subtle answer to therapy and an earlier new increase suggesting tumor markers as an essential part in the follow-up of these patients in order to optimize the patient's palliative treatment. Our results should stimulate the clinicians to rediscuss the chemosensitivity of exocrine pancreatic cancer and to perform prospective randomized studies focusing on combined gemcitabine approaches.

摘要

在首批7例接受丝裂霉素-C与吉西他滨联合动脉内/全身化疗的患者取得惊人结果的激励下,我们现在报告28例胰腺癌患者的数据,并与15例仅接受吉西他滨(1000mg/m²)治疗的患者进行比较。根据成像方法、肿瘤标志物以及体重、疼痛和卡诺夫斯基指数等生活质量参数评估肿瘤反应。每月测定肿瘤标志物,每1 - 3个月进行成像检查。局部区域/全身治疗方案包括每3周为一个周期,第1天动脉内应用丝裂霉素-C + 吉西他滨,第8天和第15天静脉应用吉西他滨。总共125个周期(平均每位患者4个周期),成像检查结果显示43%为部分缓解(n = 12),1例完全缓解(3%),25例病情稳定,11%病情稳定,18%病情进展;相关肿瘤标志物方面,20%为完全缓解,60%为部分缓解,4%病情稳定,12%病情稳定。无进展生存期通过成像方法(肿瘤标志物)确定,中位数为7.5(6)个月。在吉西他滨或吉西他滨 + 奥沙利铂有效局部区域治疗后出现新进展的二线治疗未导致新的肿瘤消退。然而,3例接受高剂量5-氟尿嘧啶或伊立替康的三线治疗试验诱导了新的抗肿瘤疗效(这些肿瘤的生存期分别> 15、> 17和> 28个月,n = 2为M1期,n = 1为T3M0期)。约75%的患者报告生活质量参数有相关改善。副作用原则上与吉西他滨单药治疗相当,只是肺部并发症发生率有升高趋势,且观察到1例溶血尿毒综合征。即使未在随机研究中进行比较,局部区域/全身联合治疗方式似乎在成像方法和肿瘤标志物所定义的客观肿瘤反应率方面更高。比较肿瘤标志物和成像对治疗的反应,CA 19-9通常对治疗显示出更快速和细微的反应,以及更早的新升高,提示肿瘤标志物是这些患者随访的重要组成部分,以便优化患者的姑息治疗。我们的结果应促使临床医生重新讨论外分泌性胰腺癌的化疗敏感性,并开展聚焦于吉西他滨联合方案的前瞻性随机研究。

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