Schüll Birgit, Scheithauer W
Klinische Abteilung für Onkologie, Universitätsklinik für Innere Medizin I, Währingergürtel 18-20, A-1090 Wien.
Acta Med Austriaca. 2002;29(4):124-31. doi: 10.1046/j.1563-2571.2002.02025.x.
To evaluate the efficacy of combined raltitrexed and oxaliplatin in vitro using 4 colorectal cell-lines and subsequently in vivo in 36 patients with advanced colorectal cancer failing palliative 5-fluorouracil/leucovorin-based chemotherapy. In the preclinical phase of this study, the efficacy of oxaliplatin and of raltitrexed as well as of 5-FU alone and in combination was evaluated in 4 different human colorectalcarcinoma cell-lines with the MTT-test (Microculture Tetrazolium Assay). In the clinical phase 36 patients with metastatic colorectal cancer, who progressed while receiving or within 6 months after withholding palliative chemotherapy with 5-FU/leucovorin +/- irinotecan were enrolled in this study. Treatment consisted of oxaliplatin 130 mg/m2 and raltitrexed 3.0 mg/m2 both given on day 1 every 3 weeks for a total of 8 courses unless prior evidence of progressive disease. A supraadditive effect was found for the experimental combination of oxalipatin and raltitrexed in 3/4 of cell lines. In the clinical phase the overall response rate was 33.3% for all 36 evaluable patients. Seventeen additional patients (47.2%) had stable disease, and only 7 (19.5%) progressed. The median progression-free survival was 6.5 months (range, 1.2 to 14.0). After a median follow-up time of 12 months, 23 patients (63.8%) are still alive. The tolerance of treatment was acceptable with only 8/36 (22%) experiencing grade 3 or 4 neutropenia. Grade 3 nonhematologic adverse reactions included peripheral sensory neuropathy in 3, asthenia in 1, diarrhea in 2, and clinically insignificant increase in serum transaminases in 2 patients, respectively. Our data suggest that the combination of oxaliplatin and raltitrexed has not only in vitro, but also in vivo in patients with progressive fluoropyrimidine/leucovorine +/- irinotecan pretreated colorectal cancer antitumor activity. Because of its favorable toxicity profile and its convenient 3-weekly outpatient administration schedule, further evaluation of this regimen seems warranted.
使用4种结肠直肠癌细胞系评估雷替曲塞与奥沙利铂联合用药的体外疗效，随后在36例接受姑息性5-氟尿嘧啶/亚叶酸钙化疗失败的晚期结直肠癌患者中评估其体内疗效。在本研究的临床前阶段，采用MTT试验（微量培养四氮唑蓝法）在4种不同的人结肠直肠癌细胞系中评估奥沙利铂、雷替曲塞以及单独使用和联合使用5-氟尿嘧啶的疗效。在临床阶段，36例转移性结直肠癌患者被纳入本研究，这些患者在接受5-氟尿嘧啶/亚叶酸钙±伊立替康姑息化疗期间或停药后6个月内病情进展。治疗方案为奥沙利铂130mg/m²和雷替曲塞3.0mg/m²，均在第1天每3周给药1次，共8个疗程，除非有疾病进展的证据。在3/4的细胞系中发现奥沙利铂和雷替曲塞的联合用药具有超相加效应。在临床阶段，36例可评估患者的总缓解率为33.3%。另有17例患者（47.2%）病情稳定，仅7例（19.5%）病情进展。无进展生存期的中位数为6.5个月（范围为1.2至14.0个月）。中位随访时间12个月后，23例患者（63.8%）仍存活。治疗耐受性可接受，仅8/36例（22%）出现3级或4级中性粒细胞减少。3级非血液学不良反应分别包括3例周围感觉神经病变、1例乏力、2例腹泻以及2例患者血清转氨酶临床意义不显著升高。我们的数据表明，奥沙利铂和雷替曲塞联合用药不仅在体外，而且在体内对经氟嘧啶/亚叶酸钙±伊立替康预处理且病情进展的结直肠癌患者具有抗肿瘤活性。由于其良好的毒性特征和方便的每3周门诊给药方案，似乎有必要对该方案进行进一步评估。
